Uas - Biokimia Teori
Uas - Biokimia Teori
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Overview
༝ most vitamins need to come from food (vit dpt dari makanan)
༝ human body either does not produce enough of them, or it does not produce
any at all.
༝ different vitamins have different roles; and they are needed in different
Quantities (Vit punya kebutuhan dan jumlah yang berbeda)
༝ Each organism has different vitamin requirements
༝ Human needs to consume vitamin C but animals do not.
༝ People need to get most of their vitamin D from exposure of sunlight, because it
isn’t available in large enough quantities of food. Human body can synthesize it
when exposed to sunlight.
༝ The liver can synthesize niacin from tryptophan; requiring 60 mg of tryptophan
to make 1 mg of niacin; it also required riboflavin; vit B 6 and iron in this process
.
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Classification of Vitamins
VITAMINS
Vitamin B1 (thiamine)
Vitamin B2 (riboflavin) Folic acid Vitamin B6 (pyridoxine)
Vitamin B3 (niacin/nicotinic acid) Vitamin B12 (cobalamine)
Pantothenic acid
Biotin 4
Characteristics of Two Types of Vitamins
Fat Soluble Vitamins Water Soluble Vitamins
Digestion and absorption Along with lipids requires bile salts Easily absorbed in intestine
Deficiency Manifest only when stores are depleted Manifest rapidly as there is no storage
Treatment of deficiency Single large doses may prevent deficiency Regular dietary supply is required
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Recommended Dietary Allowance
6
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Vitamin A
Overview
༝ Does not refer to one single vitamin but is a collection
of compounds with vitamin A activity known as
retinoids
༝ Retinoids can be found both in the human body and in some food
sources
༝ Important forms of vitamin A :
༝ Retinol (Vitamin A alcohol) key player; can be converted to other
forms
༝ Retinal (Vitamin A aldehyde)
༝ Retinoic acid (Vitamin A acid)
༝ β-Carotene (Pro-vitamin A)
༝ Not easily destroyed by heat and cooking but is readily
oxidized
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Chemical Structure
Biomolecule
Active
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Provitamin A
༝ Provitamin A some carotenoids which have
vitamin A activity
༝ Carotenoids, can be found in plants, are composed
by carotenes and related compounds; many are
precursors of vitamin A, as they can be cleaved to
yield retinaldehyde, then retinol and retinoic acid
༝ Provitamin A can be converted into vitamin A
(retinol) in the body
༝ There are > 600 types of carotenoids, but only 10%
(β-carotene, -carotene, γ-carotene) have
provitamin A activity
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Absorption, Stotage & Transportation
80-90%
Some of vitamin A
enzim retinil are r eabs or bed
ester hidrolase
from intes tine into
the enter ohepatic
circulation
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Absorption, Stotage & Transportation
hepatic stellate cells
(HSC)
enzim retinil
ester hidrolase
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Excretion
༝ Vitamin A is excreted in various forms :
༝ Bile acids feces (70%)
༝ Urine (30%)
༝ Under normal physiological conditions, the efficiency of
enteric absorption of vitamin A is high (80-95%), with 30-
60% of the absorbed amount being deposited in esterified
form in the liver
༝ Carotenoids are not found in urine and its excretion
through bile salts are very low
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Functions of Vitamin A
༝ Essential for vision (untuk penglihatan)
༝ Regulation of gene expression (ekspresi gen)
༝ Cell Growth and Differentiation (diferensi
༝ Reproduction
༝ Maintenance of epithelial cells. (jaga sel epitel
༝ Synthesis of Glycoproteins (pembentukan glikoprotein
༝ Hematopoiesis
༝ Maintenance of Immune System. Jaga sistem imun
༝ Anti-oxidant activity
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RDA of Vitamin A Kebutuhan Vit A
༝ The daily requirement of vitamin A is expressed as retinol equivalents (RE)
rather than International Units ( IU) .
༝ 1 IU = 0.3 mg of retinol
༝ 1 RE = 1 μg of retinol or 6 μg of beta carotene
༝ The recommended daily allowance (RDA)
༝ Children = 400-600 μg/day
༝ Men = 750-1000 μg /day
༝ Women = 750 μg/day
༝ Pregnancy = 1000 μg/day
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RDA of Vitamin A
Age Groups Vitamin A Age Groups Vitamin A Age Groups Vitamin A
(mcg) (mcg) (mcg)
Infant & Children
• 0 – 6 months • 375 mcg
• 7 – 11 months • 400 mcg Female Male
• 1 – 3 years • 400 mcg • 10 – 12 years • 600 mcg • 10 – 12 years • 600 mcg
• 4 – 6 years • 450 mcg • 13 – 15 years • 600 mcg • 13 – 15 years • 600 mcg
• 7 – 9 years • 500 mcg • 16 – 18 years • 600 mcg • 16 – 18 years • 600 mcg
• 19 – 29 years • 500 mcg • 19 – 29 years • 600 mcg
Pregnant
• TM 1 • 30 – 49 years • 500 mcg • 30 – 49 years • 600 mcg
• add +300 mcg
• TM 2 • 50 – 64 years • 500 mcg • 50 – 64 years • 600 mcg
• add +300 mcg
• TM 3 • 65 – 80 years • 500 mcg • 65 – 80 years • 600 mcg
• add +350 mcg
• > 80 years • 500 mcg • > 80 years • 600 mcg
Breastfeed • add +350 mcg
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Dietary Sources
Animal Sources (preform vitamin A) Vegetable sources
• Human milk sources of pro-vitamin A carotenoids
• Whole milk & dairy product : milk, • Green leafy vegetables (e.g., spinach,
butter, cream cheese amaranth, and young leaves from
• Glandular meat (liver) various sources
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Vitamin A Deficiency
༝ Vitamin A deficiency has been associated with slowed
re-epithelisation, decreased collagen synthesis and stability and
an increa sed s us ceptibility to infection.
༝ Etiology of Vitamin A deficiency : (faktor defisiensivitA)
༝ Decreas ed intake penurunan asupan
༝ Obstructive jaundice (penyakit kuning
༝ Abetalipoproteinemia *gang absorpsi lemak dan protein
༝ Cirrhosis of liver
༝ Severe malnutrition
༝ Chronic nephrosis
༝ Fat malabsorption,
༝ Acute & chronic infection
༝ Smoking (defisiensi vit krn merokok)
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Deficiency Manifestations of Vitamin A
༝ The deficiency manifestations are related to the eyes, skin and
growth.
Follicular Hyperkeratosis
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Therapeutic Doses Vitamin A
༝ Vitamin A supplementation for eye disorders prevention
༝ 6 - 12 months blue capsule vitamin A (100,000 SI)
༝ 1 2 - 59 months red capsule vitamin A (200,000 SI)
༝ Therapeutic dose for eye disorders night blindness – corneal xerosis
༝ 1 day
st
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Toxicity
༝ Excessive intake Lead to toxicity. (asupan lebih > akibatkan
toksisitas)
༝ Preform vitamin A essential nutrient potentially causing
toxicity
༝ Symptoms of toxicity affect the central nervous system; the liver;
calcium homeostasis; and the skin.
༝ Overconsumption of beta carotene from food sources may cause
skin to turn yellow but is not harmful
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Toxicity
༝ Acute hypervitaminosis A
༝Adult : Retinol > 200 mg (660.000 IU/single dose)
༝Children : Retinol > 100 mg (330.000 IU/single dose)
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Interaction with Other Nutrients
༝ Vitamin A supplementation will lead to hematopoiesis state in
anemia (suplemen vit a tinggi > akibatkan anemia)
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Vitamin D
Overview
༝ Known as calciferol, 1,25-dihydroxy vitamin D
(calcitriol), vitamin D3 (Cholecalciferol), vitamin D2
(ergocalciferol) >bentuk vit d
༝ It is pres ent in animals , plants & ha s s everal
important functions in the body.
(ada beberapa di hewan dan tumbuh”an dan
beberapa penting untuk tubuh)
༝ Considered as hormone
Vit d bisa disintesis di dlm kulit > teraktivasi oleh
sinar matahari
Dikenal sbg sunshine vitamin > aktid krn kena
sinar matahari (sumber vit d)
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༝ Vitamin D is derived from 7-dehydrocholesterol (ergosterol) by
the action of UV radiations (vitamin d jenis ergosterol yang
bisa teraktivasi oleh sinar uv).
༝ There are two chemical forms of vitamin D : (bentukprovitaminD)
༝ Vitamin D2 (Ergocalciferol) - found in plants > diproduksi tumbuhan dlm
bentuk yang diiradiasi oleh tnaman yg memiliki ergosterol steroid
༝ Vitamin D3 (Cholecalciferol) - found in animals >diproduksi scr fotokimia
diaktivasi oleh sinar uv > precursor ergosterol
༝ Ergocalciferol and cholecalciferol are sources for vitamin D
activity and are referred to as provitamins. (sumber
aktivitas vitamin D > disebut provitamin)
༝ Transformation from inactive provitamin to the active vitamin is
accomplished by the ultraviolet rays.(transformasi dari inaktif
provitamin mjd aktif vitamin dibantu oleh sinar matahri
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Metabolism & Biochemical Function of Vitamin D
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Regulation (pengaturan) ofVitaminD
༝ Regulation of calcitriol synthesis is done by:
༝ Its own concentration—by feedback inhibition of 1 α-hydroxylase
༝ Parathyroid hormone (PTH)
༝ Serum phosphate level
༝ PTH is released in low serum Ca and induces the production of
calcitriol
༝ Calcitriol regulates its own concentration, inhibit “1 α-hydroxylase”
and stimulates 24,25-di-OH-D3 (Secalcifediol) , which is inactive.
༝ Mode of action of calcitriol
༝ Calcitriol acts as a steroid hormone receptors.
༝ This binding is specific and reversible.
༝ The receptor has a specific binding site on DNA.
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Vitamin D Is Considered As A“Prohormone” &
Calcitriol (1,25-di-oh-d3) As AHormone
༝ Like hormones, calcitriol has definite “target” organs like small intestine,
bones and kidneys to act upon. It is produced in one organ and acts
upon distant target organs for its activity (property of hormone).
༝ Calcitriol resembles steroid hormone in its mode of action,
i.e. nuclear action.
༝ Calcitriol maintains calcium homeostasis along with—two other
protein hormones parathormone (PTH) and calcitonin.
༝ Parathormone (PTH) is considered as a “tropic” hormone for calcitriol, it
increases the calcitriol production by stimulating the enzyme “1 α-
hydroxylase” in kidney tubules.
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Action of Calcitriol on Calcium Homeostasis
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Functions of Vitamin D Fungsi Vit D)
༝ Calcium and Phosphorus Homeostasis
༝ Calcium and Phosphorus absorption (small intestine)
༝ Calcium resorption (bone and kidney)
༝ Maintain blood calcium levels
༝ Bone formation
༝ Stimulate calcium uptake for deposition as calcium phosphate
(Osteoblasts: bone-forming cells)
༝ Hormone
༝ Regulation of gene expression
༝ Cell growth
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Functions of Vitamin D
༝ Action of calcitriol on the intestine: Calcitriol increases the intestinal
absorption of calcium and phosphate.
༝ Action of calcitriol on the bone : In the osteoblast of bone, calcitriol
stimulate calcium uptake for deposition and calcium phosphate.
Calcitriol is essential for bone formation. (Dalam osteoblas tulang,
kalsitriol merangsang pengambilan kalsium untuk deposisi dan kalsium
fosfat.Calcitriol sangat penting untuk pembentukan tulang)
༝ Action of calcitriol on the kidney (ginjal) : Calcitriol is also involved in
minimizing the excretion of calcium and phosphate through the kidney,
by decreasing their excretion and enhancing reabsorption.
(Calcitriol juga terlibat dalam meminimalkan ekskresi kalsium dan
fosfat melalui ginjal,dengan mengurangi ekskresi dan meningkatkan
reabsorpsi)
(Mengatur ekskresi bisa ditingkatkan / diturunkan)
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RDA of Vitamin D
༝ The daily requirement of vitamin D is expressed as microgram or IU
༝ 1 µg of vitamin D = 40 International Units
༝ Children : 10µg/day (400 IU)/day
༝ Adults : 5-10 μg/ day (200IU)/day
༝ Pregnancy and lactation : 10µg/day
༝ Over 70years : 600 IU/day
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RDA of Vitamin D
Age Groups Vitamin D Age Groups Vitamin D Age Groups Vitamin D
(mcg) (mcg) (mcg)
Infant & Children
• 0 – 6 months • 5 mcg
• 7 – 11 months • 5 mcg Female Male
• 1 – 3 years • 15 mcg • 10 – 12 years • 15 mcg • 10 – 12 years • 15 mcg
• 4 – 6 years • 15 mcg • 13 – 15 years • 15 mcg • 13 – 15 years • 15 mcg
• 7 – 9 years • 15 mcg • 16 – 18 years • 15 mcg • 16 – 18 years • 15 mcg
• 19 – 29 years • 15 mcg • 19 – 29 years • 15 mcg
Pregnant
• TM 1 • 30 – 49 years • 15 mcg • 30 – 49 years • 15 mcg
• no add
• TM 2 • 50 – 64 years • 15 mcg • 50 – 64 years • 15 mcg
• no add
• TM 3 • 65 – 80 years • 20 mcg • 65 – 80 years • 20 mcg
• no add
• > 80 years • 20 mcg • > 80 years • 20 mcg
Breastfeed • no add
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Functions of Vitamin D
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Deficiency of Vitamin D
Concentration of Vitamin D level (ng/ml)
༝Normal level of vitamin D
: 30 ng/ml
༝Vitamin D insufficiency
: 20 - 29 ng/ml
༝Vitamin D deficiency
: 10 - 19 ng/ml
༝Severe deficiency
: < 10 ng/ml
༝Toxicity : > 150ng/ml
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Deficiency of Vitamin D
Causes for Vitamin D Deficiency
༝People who are not exposed to sunlight properly. (orang yg tdk terpapar
sinar matahri dlm waktu yang cukup) > penggunaan baju, sunblok
༝ Nutritional deficiency of calcium or phosphate (defisiensi kalsium atau
fosfat)
༝ Malabsorption of vitamin (obstructive jaundice and steatorrhea) and high
phytate content in diet reduce the absorption of vitamin. (malabsorpsi
vitamin, makanan tinggi fitat > mengurangi absorpsi vit d)
༝ Deficient renal absorption of phosphates (gangguan absorpsi vit d yg
ada di ginjal > disebabkan krn absorpsi fosfat)
༝Certain disease such as SLE (Systemic Lupus Erythematosus),
immobilization, melanoma
༝ Application of sunscreen lotions or presence of dark skin color decrease
this synthesis (penggunaan sunscreen, org berkulit gelap > pengaruhi 41
Deficiency of Vitamin D
༝ Children rickets (defisiensi vit d pd anak” disebut riketsia
> tulang jd lemah dan tdk padat, lentur) > tjd krn inadekuat
vit d dalam jangka waktu lama > akibatkan gang. Untuk
menjaga jml ca dan fosfor di dlm tulang
༝ Others :
༝ osteoporosis, diabetes, cancer (colon, breast, ovarium,
prostate)
autoimun disease (asthma, rheumatoid arthritis, multiple
sclerosis, psoriasis),proximal myophaty, cardiovascular
disease, hypertension,
etc
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Hypervitaminosis D
༝ Hypervitaminosis D > tjd pemberian dosis tinggi
༝ Among the vitamins, vitamin D is the most toxic in
overdoses(10-100 times RDA)
༝ Calcification of soft tissue
༝ Lungs, heart, blood vessels
༝ Hardening of arteries, stone formation in kidneys
༝ Does not occur from sunlight or dietary sources
༝ Does occur with supplementation
༝ In general, vitamin D supplement are not recommended.
༝ Upper limit: 50 micrograms a day (pemberian suplemen
tdk boleh lbh dari 50 microgram per hari)
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Hypervitaminosis D
Toxic effects of hypervitaminosis D include
༝ Doses above 10,000IU/day for long period causes toxicity.
༝ Demineralization of bone (resorption) and increased calcium
absorption from the intestine, leading to elevated calcium in
plasma (hypercalcemia).
༝ Prolonged hypercalcemia is associated with deposition of
calcium in many soft tissues such as kidney and arteries.
༝ Formation of stones in kidneys (renal calculi).
༝ Symptoms include weakness, polyuria, intense thirst, difficulty
in speaking, hypertension, loss of appetite, loss of weight etc.
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Vitamin E
Overview
༝ Naturally occurring anti-oxidant. (Dikenal sebagai Antioksidan)
༝ Evan s & Bishop(1936) - isolated active vitamin.
༝ Named – Tocopherol. (Dikenal sebagai Tokoferol )
༝ (Tokos : childbirth, pherein: to bring ,ol : alcohol)
༝ Anti-sterility vitamin- Essential for normal reproduction in
many animals.
(dikenal sebagai vitamin berkaitan dgn kesuburan > berperan dlm
reproduksi normal pd hewan dan manusia)
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Chemistry of Vitamin E
༝ Elucidated by Paul Karrer, awarded Nobel Prize in 1937.
༝ Name given to a group of tocopherols & tocotrienols .
༝ About eight tocopherols have been identified- α, β, γ, δ etc.
༝ α-tocopherol is the most active.
༝ Derivatives of 6-hydroxy chromane (tocol) ring with
isoprenoid side chain.
༝ antioxidant property is due to the chromane ring.
α-tocopherol 47
Chemistry of Vitamin E
༝ Elucidated by Paul Karrer, awarded Nobel Prize in 1937.
༝ Name given to a group of tocopherols & tocotrienols .
(Vit E ada dlm bentuk tokoferol dan tokotrienol)
༝ About eight tocopherols have been identified- α, β, γ, δ etc.
༝ α-tocopherol is the most active.
(Ada tokoferol yang sdh diidentifikasi : alfa, beta, gamma, tetra, yang paling
aktif adl alfa tokoferol)
༝ Derivatives of 6-hydroxy chromane (tocol) ring with
isoprenoid side chain.
(Vit E terdiri dari tocol atau cincin hidroksil kromanil yg
akan berikatan dengan rantai samping isoprenoid)
༝ antioxidant property is due to the chromane ring.
(Vit E punya aktivitas antioksidan karena punya cincin kromanol) 47
Chromanol ring
Isoprenoid chain Isoprenoid chain
V
i
t
a
m
e
r
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Diabsorpsi paling banyak sumbernya dari / paling mudah diabsorpsi dr
tumbuhan
Dari hewan yang diabsorpsi di usus halus sangat lemah / sangat sedikit
Absorpsi > butuh bantuan garam empedu
Proses absorpsi dan transport butuh karier > karier sbg pengangkut >
dibantu cilomikron > cilomikron bantu edarkan vit e ke dlm jaringan /
organ yg membutuhkan
Vit e bisa disimpan di jaringan adipose
Tjd katabolisme > akan akibatkan oksidasi cincin kromanol dan rantai
samping isoprenolol
Vit e akan diekskresikan melalui bantuan garam empedu yang terkonjugasi
asam glukoronat dan terekskresi melalui urin dan keringat
Berperan dlm proses keseimbangan jar perifer, sbg antioksidan dlm :
1. Membrane Sel
2. Jaringan
3. Saluran Pernafasan
4. DNA
5. Jantung
6. Jaringan Lainnya
Major Functions of Vitamin E in the Body
༝ Antioxidant (Fungsi utama = sbg antioksidan)
༝ Vitamin E is very uns table, eas ily oxidized
(Karakteristik = sangat tdk stabil, mudah teroksidasi)
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Fungsi Vitamin E
• Sbg antioksidan yg kuat > membantu / berperan penting dlm struktur
membrane sel dan integritas membrane sel
• Sbg scavenger dr radikal bebas > melindungi sel darah merah dr proses
hemolisis
• Menurunkan laju penuaan dan meningkatkan sistem imun
• Bantu lindungi oksidasi LDL > menurunkan resiko tjd arterosklerosis >
direkomendasi sbg terapi dlm penangangan diet penyakit jantung
• Berperan dlm fungsi reproduksi dan melindungi / mencegah kemandulan
• Mencegah tjd penyakit kronik spt kanker dan penyakit hati
• Lindungi hepar dr kerusakan seluler krn adanya interaksi dgn komponen
toksik
• Vit E dgn bantuan biotin berperan dlm proses pertumbuhan rambut
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RDA of Vitamin E (Kebutuhan)
༝ Males – 10mg/day.
༝ Females – 8mg/day.
༝ Pregnancy - 10mg/day.
༝ Lactation- 12mg/day.
༝ 15 mg vitamin E = 33 IU
༝ Pharmacological dos e = 200-400 IU/day.
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RDA of Vitamin E
Age Groups Vitamin E Age Groups Vitamin E Age Groups Vitamin E
(mg) (mg) (mg)
Infant & Children
• 0 – 6 months • 4 mg
• 7 – 11 months • 5 mg Female Male
• 1 – 3 years • 6 mg • 10 – 12 years • 11 mg • 10 – 12 years • 11 mg
• 4 – 6 years • 7 mg • 13 – 15 years • 15 mg • 13 – 15 years • 12 mg
• 7 – 9 years • 7 mg • 16 – 18 years • 15 mg • 16 – 18 years • 15 mg
• 19 – 29 years • 15 mg • 19 – 29 years • 15 mg
Pregnant
• TM 1 • 30 – 49 years • 15 mg • 30 – 49 years • 15 mg
• no add
• TM 2 • 50 – 64 years • 15 mg • 50 – 64 years • 15 mg
• no add
• TM 3 • 65 – 80 years • 15 mg • 65 – 80 years • 15 mg
• no add
• > 80 years • 15 mg • > 80 years • 15 mg
Breastfeed • add 4 mg
• add 4 mg
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Dietary S ources of Vitamin E
Richest source (sumber terkaya = minyak dr tumbuh”an atau
kacang” an)
༝ Vegetable oils – Wheat Germ Oil, Sunflower Oil, Cotton Seed Oil,
Olive oil.
༝ Coconut oils – relatively low.
༝ Fish liver oils – devoid.
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Vitamin E Deficiency Manifestations
༝ Rarely happened (sangat jarang tjd)
༝ Major Symptoms :
༝Erythrocyte hemolysis and hemolytic anemia, disruption of red
blood cell membranes, perhaps due to polyunsaturated fatty
acids (PUFAs) oxidation
༝Hemolytic anemia – increased red blood cell fragility
༝Acute hepatic necrosis- Diets low in cystine and rich in
polyunsaturated fatty acids can cause hepatic necrosis
༝Muscular dystrophy- Muscular weakness & creatinuria.
༝Sterility: reproductive failure
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Defisiensi Vit E
Akibatkan hemolisis eritrosit dan anemia hemolitik
• tjd karena ada kerusakan sel darah merah krn ada oksidasi dr
lemak utamanya dlm bentuk PUFA
Hemolitik anemia tjd krn kerapuhan sel darah merah
Nekrosis hepatic yg akut yg disebabkan kalo ada kondisi mengikuti
diet rendah makanan sumber sistein dan tinggi PUFA
Muscular distrofi yg disebabkan karena kelemahan muskural dan
kreatinin urea
Kemandulan disebabkan krn kegagalan dlm proses reproduksi
Hypervitaminosis E
༝ Toxicity rare: wide range of safe intake compared to other
fat soluble vitamins
༝ Vitamin E is one of the most popular nutrient supplements.
There are many health claims for supplementation –
slowing of the aging process or an improvement in sexual
potency.
Doses above 1000 IU/day, cause –
༝ Tendency of hemorrhage, as it is a mild anti-coagulant.
༝ Minor Neurological symptoms..
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Vitamin K
Overview
༝ Vitamin K is the only fat soluble vitamin with a specific coenzyme
function. (Adalah vitamin larut lemak yang memiliki fungsi sbg koenzim)
༝ Produce by intestinal bacteria Diproduksi oleh bakteri di usus halus
༝ Required for the production of blood clotting factors, essential for
coagulation. Named as antihemorrhagic vitamin.
(Berperan penting dlm proses pembekuan darah / koagulasi > disebut sbg
antihemoragik)
༝ Naphthoquinone derivatives, with a long isoprenoid side chain.
62
Chemistry of Vitamin K
Exists in different forms – ( Bentuk
Vitamin K)
༝ Vitamin K1 - Phylloquinone
༝ present in plants (ada pd tumbuh”an)
༝ has 20C chain
༝ Vitamin K2 - Menaquinone
༝ present in animal (berasal dr hewan)
༝ produced by intestinal bacteria
༝ has 30C chain
༝ Vitamin K3 - Menadione
༝ water soluble synthetic form, (bentuk sintetik
vit k yg larut air)
༝ complexed to improve s tability
༝ no side chain 63
Absorption, Transportation & Excretion of
Vitamin K
༝ Absorption occurs in the intestine in the presence of bile salts.
(Absorpsi tjd di usus halus, dibantu garam empedu)
༝ The transportation from intestine is carried out through
chylomicrons.
(Transportasi dr intestine ke jar/organ lain yg membutuhkan > dibantu
/ diangkut oleh cilomikron)
༝ Storage occur in liver and from liver transportation to peripheral
cells is carried out bound with beta lipoproteins.
(vit k akan disimpan di hepar > akan ditranspor ke t4 yg membutuhkan, akan
dibantu oleh sel di jar perifer)
༝ Excretion primarily through bile, small amount urine
(Ekskresi dibantu oleh garam empedu, diekskresikan melalui urin dlm jlm
sedikit) 64
Functions of Vitamin K
༝ Necessary for coagulation
༝ Factors depended are :
༝ Factor II
༝ Factor VII
༝ Factor IX Synthesized by Liver as Zymogens
༝ Factor X
༝ It brings about the post-translational modification.
༝ Vitamin K is converted to hydroquinone in liver by dehydrogenase
using NADPH then acts as a coenzyme for the carboxylation of
glutamic acid residue, catalysed by a carboxylase.
65
Fungsi utama = antihemoragik vitamin > berperan dlm
proses koagulasi / pembekuan darah
Berperan dlm modifikasi post translational
Berperan sbg koenzim > saat disimpan di hepar akan
disimpan dlm bentuk hidrokuinon > hidrokuinon akan
dibantu enzim dehydrogenase dgn bantuan NADPH yang
akan berperan sbg koenzim untuk mereaksi karboksilasi
as glutamate yg akan dibantu/dikatalisis enzim
karboksilase
Functions of Vitamin K
༝ Calcium binding protein
༝ Vitamin K dependent gamma
carboxylation neces s ary for
osteocalcin, structural protein of
Kidney, lung and spleen.
༝ Stimulates bone formation and
decreases bone resorption.
༝ γ-carboxyglutamate is inhibited by
dicoumarol, an anticoagulant.
69
Peran Vit K dlm Pembentukan Darah
Faktor pembekuan darah bisa disintesis hepar dlm bentuk inaktif
precursor > Vit k bantu proses konversi jd bentuk aktif
residu dr asam karboksil glutamate akan mampu bergabung dgn
kalsium ion membentuk ikatan komplek
ikatan antara protrombin dan kalsium akan berikatan pd fosfolipid
di permukaan membrane pd platelet
proses konversi tsb dpt meningkatkan proses konversi protrombin jd
thrombin dlm bentuk enzim aktif dan akibatkan pembentukan
fibrinogen mjd fibrin yang akan berperan dlm proses pembekuan
darah
Dietary Sources of Vitamin K
༝ Green leafy vegetables are good dietary sources. ( Sayuran
berdaun hijau)
༝ Vitamin K is present in vegetable oils and is particularly rich in
olive, canola, and soybean oils. (Minyak sayur, minyak kacang”an)
༝ Some amount is contributed by intestinal bacteria
(Beberapa vit k bisa diproduksi oleh bakteri di usus)
71
72
Gambaran absorpsi vitamin k
Sumber = tanaman, bakteri intestine, hewan, sintetik
> akan diabsorpsi ke usus halus > diangkut dgn
dibantu cilomikron > penyimpanan di hepar > dr hepar
akan diedarkan untuk proses tertentu (pembentukan
dan pertumbuhan tulang, pembekuan darah)
RDA of Vitamin K
༝ The recommended daily allowance (RDA) is 50-100 mg/day
༝ Available in normal diet.
༝ Requirement increases in :
༝ Liver dis orders
༝ Patients on prolonged antibiotic therapy, bile acid s eques trants .
Peningkatan keb vitamin K tjd krn gangguan pd hepar, pasien dgn pemberian
antibiotic dlm jangka waktu lama (perlu suplementasi vitamin K)
74
RDA of Vitamin K
Age Groups Vitamin K Age Groups Vitamin K Age Groups Vitamin K
(mcg) (mcg) (mcg)
Infant & Children
• 0 – 6 months • 5 mcg
• 7 – 11 months • 10 mcg Female Male
• 1 – 3 years • 15 mcg • 10 – 12 years • 35 mcg • 10 – 12 years • 35 mcg
• 4 – 6 years • 20 mcg • 13 – 15 years • 55 mcg • 13 – 15 years • 55 mcg
• 7 – 9 years • 25 mcg • 16 – 18 years • 55 mcg • 16 – 18 years • 55 mcg
• 19 – 29 years • 55 mcg • 19 – 29 years • 65 mcg
Pregnant
• TM 1 • 30 – 49 years • 55 mcg • 30 – 49 years • 65 mcg
• no add
• TM 2 • 50 – 64 years • 55 mcg • 50 – 64 years • 65 mcg
• no add
• TM 3 • 65 – 80 years • 55 mcg • 65 – 80 years • 65 mcg
• no add
• > 80 years • 55 mcg • > 80 years • 65 mcg
Breastfeed • no add
• no add
75
Deficiency of Vitamin K
༝ Deficiency: increased bleeding and hemorrhage
༝ rare, they may occur in some individuals when antibiotic
medications kill the intestinal bacteria that produce the vitamin.
༝ Vitamin K deficiency are common in newborns. Parenteral
treatment with vitamin K is recommended at birth.
77
• Bisa disebabkan krn penggunaan antibiotic dan obat” gol sulfa drugs > menekan
pertumbuhan vit k, Menekan pertumbuhan bakteri usus yg produksi vitamin K shg
nantinya tdk ada vit k yg bisa diproduksi dlm jml adekuat
• Adanya malabsorpsi dan obstruksi pd jalur biliar > jaundice obstruktif, seliak
disease
• Kondisi setelah kelahiran > kondisi Hypoprothrombinemia dan adanya
perdarahan yg tjd krn defisiensi vitamin k
• Pd kondisi post natal protrombin cenderung sedikit > akibatkan perdarahan
atau hemorea yg tjd pd bayi baru lahir > tjd pd bayi yg lahir premature
• Fetal warfarin sindrom tjd krn adanya paparan thd warfarin > saat ibu itu
hamil dia konsumsi obat”an dgn kandungan warfarin > warfarin terdisposisi
ke dlm janin dan akibatkan sindrom tsb
• Warfarin dan dekomarol dpt akibatkan proses garmakarboksilasi > dpt
menggangu proses koagulasi.pembekuan darah
Causes for Vitamin K Deficiency
༝ Decreased intake. (Intake kurang)
༝ Malabsorption of lipids- (Malabsorpsi lemak krn beberapa kondisi)
༝ Results from obstructive Jaundice, chronic pancreatitis, sprue, etc.
༝ Prolonged antibiotic therapy and gastrointestinal infections with
diarrhea. (Penggunaan antibiotic dan ada infeksi dr gastrointestinal disertai
diare)
༝ Treatment of pregnant women with warfarin can lead to fetal
bone abnormalities. (Pemberian warfarin pd ibu hamil > sebabkan
gangguan pd janin)
༝ Prolongation of prothrombin time and delayed clotting time, is
vitamin K deficiency. (Ada proses pembekuan darah yg lama / proses
prolongasi dr konversi protrombin akibat defisiensi vit k)
79
Hypervitaminosis K
༝ The toxic effect is due to increased breakdown of RBC.
(Disebabkan krn proses kerusakan sel darah merah)
༝ Large quantities of menadione result in toxicity.
(Krn konsumsi vit k dlm bentuk menadion > sebabkan toksisitas)
༝ Hypervitaminosis K: (Menyebabkan beberapa kondisi :)
༝ Thrombosis,
༝ Hemolytic anaemia
༝ Hemolysis
༝ Hyperbilirubinemia Jaundice, particularly in infants.
༝ Kernicterus and brain damage (kerusakan otak)
80
Kanker kulit krn paparan sinar UV > bgm proses sinar uv sebabkan kanker kulit
Sinar UV ada UV A, UV B, UV C
Sinar UV C bisa diserap oleh atmosfir sblm mencapai tanah
Sinar UV yg bisa masuk/ menembus sel kulit = UV A / UV B
Yg berpotensi sebabkan kanker kulit adalah UV A dan UV B
Proses :
• Yg dilihat adl waktu berjemur > yg diperlukan pd panjang gelombang tertentu
yg bisa bantu proses aktivasi vitamin K > bisa dipantau lewat aplikasi untuk
deteksi / perkirakan panjang gelombang sinar uv pd jam berapa
• Waktu berjemur mempengaruhi adanya proses aktivasi vitamin D
• Panjang gelombang sinar uv bisa pengaruhi kanker kulit
• Kalo tjd paparan sinar uv berlebih > yg bisa diamati adl adanya sun burn (kulit
spt terbakar), kulit terasa lebih gelap
• Sinar uv tdk langsung sebabkan kanker kulit krn ada faktor lain
• Kanker salah satunya kanker kulit > tdk hanya single case tapi juga bisa
disebabkan krn faktor pencetus lainnya seperti riwayat keluarga, paparan bahan
kimia lainnya, warna kulit, daya tahan tubuh
• Saat mau keluar rumah dianjurkan pakai sun block / tabir surya untuk
melindungi dari sinar matahari > di dlm rumah juga pakai sunblock karena sinar
uv bisa menembus dari jendela
• Panjang gelombang diatas 320 an > bisa merusak kulit dan akibatkan kanker
kulit
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research / issue of topics we
discussed
༝ Overview (characteris tic, metabolis m,
nutrient-interaction)
༝ Daily needs & deficiency
༝Dietary source and its specific benefits
༝ Please cite your references,
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༝ Submit through HELTI
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@dianmuninggar
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82
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Thank you and have a great rest of the day and remaining week!
Stay healthy, and keeping your distance to stay safe.
Further question ?
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83
Fat- Soluble Vitamins
Nutrition Biochemistry
2021
Dian Luthfita Prasetya Muninggar
Nutrition Department
Politeknik Kesehatan Kemenkes Semarang
“
Vitamin vital for life
an organic compounds that are needed in small
quantities to sustain life.
2
Overview
༝ most vitamins need to come from food
༝ human body either does not produce enough of them, or it does not produce
any at all.
༝ different vitamins have different roles; and they are needed in different
quantities
༝ Each organism has different vitamin requirements
༝ Human needs to consume vitamin C but animals do not.
༝ People need to get most of their vitamin D from exposure of sunlight, because it
isn’t available in large enough quantities of food. Human body can synthesize it
when exposed to sunlight.
༝ The liver can synthesize niacin from tryptophan; requiring 60 mg of tryptophan
to make 1 mg of niacin; it also required riboflavin; vit B 6 and iron in this process
.
3
• sebagian besar vitamin harus berasal dari makanan
• tubuh manusia tidak cukup memproduksinya, atau tidak
menghasilkan
• vitamin yang berbeda memiliki peran yang berbeda; dan
vitamin dibutuhkan dalam jumlah yang berbeda
• Setiap organisme memiliki kebutuhan vitamin yang
berbeda
• Manusia perlu mengkonsumsi vitamin C tetapi hewan
tidak, hewan punya jalur sintesis vit C sendiri
• Manusia perlu mendapatkan sebagian besar vitamin D
mereka dari paparan sinar matahari, karena vit D tidak
banyak ditemukan dimakanan
• Hati dapat mensintesis niasin dari triptofan
(membutuhkan vitamin B6 dan zat besi); membutuhkan
60 mg triptofan
Classification of Vitamins
VITAMINS
Vitamin B1 (thiamine)
Vitamin B2 (riboflavin) Folic acid Vitamin B6 (pyridoxine)
Vitamin B3 (niacin/nicotinic acid) Vitamin B12 (cobalamine)
Pantothenic acid
Biotin 4
Characteristics of Two Types of Vitamins
Fat Soluble Vitamins Water Soluble Vitamins
Digestion and absorption Along with lipids requires bile salts Easily absorbed in intestine
Deficiency Manifest only when stores are depleted Manifest rapidly as there is no storage
Treatment of deficiency Single large doses may prevent deficiency Regular dietary supply is required
6
Characteristics of Two Types of Vitamins
Fat Soluble Vitamins Water Soluble Vitamins
Digestion and absorption membutuhkan garam empedu untuk Mudah diserap di usus
mengikat lemak
Carrier protein Present Tidak ada protein pembawa
8
9
Vitamin A
Overview
༝ Does not refer to one single vitamin but is a collection
of compounds with vitamin A activity known as
retinoids
༝ Retinoids can be found both in the human body and in some food
sources
༝ Important forms of vitamin A :
༝ Retinol (Vitamin A alcohol) key player; can be converted to other
forms
༝ Retinal (Vitamin A aldehyde)
༝ Retinoic acid (Vitamin A acid)
༝ β-Carotene (Pro-vitamin A)
༝ Not easily destroyed by heat and cooking but is readily
oxidized
9
Overview
• Tidak mengacu pada satu vitamin tunggal tetapi merupakan
kumpulan senyawa dengan aktivitas vitamin A yang dikenal
sebagai retinoid
• Retinoid dapat ditemukan baik di tubuh manusia maupun di
beberapa sumber makanan
• Bentuk penting vitamin A :
1. Retinol (Vitamin A alkohol) pemain kunci; dapat
dikonversi ke beberapa bentuk vitamin A
2. Retina (Vitamin A aldehida)
3. Asam retinoat (asam vitamin A)
4. β Karoten (Pro vitamin A)
• Tidak mudah hancur oleh panas dan pemasakan tetapi
mudah teroksidasi
9
Chemical Structure
Biomolecule
Active
16
Preform Vitamin A
༝ Retinol : nama generic dari semua retinoid yang memiliki
aktivitas biologis all-trans retinol
༝ Disebut retinol karena memiliki fungsi khusus di retina
༝ vitamin A alami atau yang terkandung dalam bahan makanan
umunya ditemukan dalam bentuk rantai panjang ester retinil
(retinil palmitat)
༝ vitamin A berasal dari prekusor/provitamin A yang dikonsumsi
oleh hewan/manusia akan menjadi preform vitamin A
༝ retinoid terdiri dari retinol, retinaldehid, dan asam
retinoat (bentuk vitamin A), hanya ditemukan dalam
makanan yang bersal dari hewan
17
Provitamin A
༝ Provitamin A some carotenoids which have
vitamin A activity
༝ Carotenoids, can be found in plants, are composed
by carotenes and related compounds; many are
precursors of vitamin A, as they can be cleaved to
yield retinaldehyde, then retinol and retinoic acid
༝ Provitamin A can be converted into vitamin A
(retinol) in the body
༝ There are > 600 types of carotenoids, but only 10%
(β-carotene, -carotene, γ-carotene) have
provitamin A activity
18
Provitamin A
༝ Provitamin A beberapa karotenoid yang
memiliki aktivitas vitamin A
༝ karoteoind, dapat ditemukan pada tumbuhan,
tersusun oleh karoten dan senyawa terkait; banyak
yang merupakan precursor vitamin A, karena dapat
dipercah menjadi retinaldehid, kemudian retinol
dan asam retinoat
༝ Provitamin A dapat diubah menjadi vitamin A
(retinol) di dalam tubuh
༝ ada > 600 jenis karotenoid, tapi hanya 10%
(β-carotene, -carotene, γ-carotene)
memiliki aktivitas provitamin A
19
Absorption, Stotage & Transportation
80-90%
Some ofvitamin A
enzim retinil are reabsorbed
ester hidrolase
from intestine into
the enterohepatic
circulation
20
Absorption, Stotage & Transportation
hepatic stellate cells
(HSC)
enzim retinil
ester hidrolase
21
Excretion
༝ Vitamin A is excreted in various forms :
༝ Bile acids feces (70%)
༝ Urine (30%)
༝ Under normal physiological conditions, the efficiency of
enteric absorption of vitamin A is high (80-95%), with 30-
60% of the absorbed amount being deposited in esterified
form in the liver
༝ Carotenoids are not found in urine and its excretion
through bile salts are very low
22
Excretion
༝ Vitamin A diekresikan dalam berbagai bentuk:
༝ asam empedu feces (70%)
༝ Urine (30%)
༝ dalam kondisi fisiologis normal, efisiensi penyerapan
enteric vitamin A tinggi (80-95%), dengan 30-60% dari
jumlah yang diserap disimpan dalam esterifikasi
terbentuk di hati
༝ karotenoid tidak ditemukan dalam urin dan
ekskresinya melalui garam empedu sangat rendah
23
Functions of Vitamin A
༝ Essential for vision
༝ Regulation of gene expression
༝ Cell Growth and Differentiation
༝ Reproduction
༝ Maintenance of epithelial cells.
༝ Synthesis of Glycoproteins
༝ Hematopoiesis
༝ Maintenance of Immune System.
༝ Anti-oxidant activity
24
Functions of Vitamin A
༝ penting untuk penglihatan
༝ regulasi ekspresi gen
༝ pertumbuhan dan diferensiasi sel
༝ Reproduksi
༝ penerilharaan sel epitel
༝ Sintesis glikoprotein
༝ Hematopoiesis
༝ pemeliharaan sistem kekebalan tubuh
༝ aktivitas anti-oksidan
25
RDA of Vitamin A
༝ The daily requirement of vitamin A is expressed as retinol equivalents (RE)
rather than International Units ( IU) .
༝ 1 IU = 0.3 mg of retinol
༝ 1 RE = 1 μg of retinol or 6 μg of beta carotene
༝ The recommended daily allowance (RDA)
༝ Children = 400-600 μg/day
༝ Men = 750-1000 μg /day
༝ Women = 750 μg/day
༝ Pregnancy = 1000 μg/day
26
RDA of Vitamin A
༝ kebutuhan harian vitamin A dinyatakan sebagai retinol equivalen (RE)
bukan satuan internasional (IU).
༝ 1 IU = 0.3 mg of retinol
༝ 1 RE = 1 μg of retinol or 6 μg of beta carotene
༝ The recommended daily allowance (RDA)
༝ Children = 400-600 μg/day
༝ Men = 750-1000 μg /day
༝ Women = 750 μg/day
༝ Pregnancy = 1000 μg/day
27
RDA of Vitamin A
Age Groups Vitamin A Age Groups Vitamin A Age Groups Vitamin A
(mcg) (mcg) (mcg)
Infant & Children
• 0 – 6 months • 375 mcg
• 7 – 11 months • 400 mcg Female Male
• 1 – 3 years • 400 mcg • 10 – 12 years • 600 mcg • 10 – 12 years • 600 mcg
• 4 – 6 years • 450 mcg • 13 – 15 years • 600 mcg • 13 – 15 years • 600 mcg
• 7 – 9 years • 500 mcg • 16 – 18 years • 600 mcg • 16 – 18 years • 600 mcg
• 19 – 29 years • 500 mcg • 19 – 29 years • 600 mcg
Pregnant
• TM 1 • 30 – 49 years • 500 mcg • 30 – 49 years • 600 mcg
• add +300 mcg
• 50 – 64 years • 500 mcg • 50 – 64 years • 600 mcg
• TM 2 • add +300 mcg
• 65 – 80 years • 500 mcg • 65 – 80 years • 600 mcg
• TM 3 • add +350 mcg
• > 80 years • 500 mcg • > 80 years • 600 mcg
Breastfeed • add +350 mcg
28
Dietary Sources
Animal Sources (preform vitamin A) Vegetable sources
• Human milk sources of pro-vitamin A carotenoids
• Whole milk & dairy product : milk, • Green leafy vegetables (e.g., spinach,
butter, cream cheese amaranth, and young leaves from
• Glandular meat (liver) various sources
29
Vitamin A Deficiency
༝ Vitamin A deficiency has been associated with slowed
re-epithelisation, decreased collagen synthesis and stability and
an increased susceptibility to infection.
༝ Etiology of Vitamin A deficiency :
༝ Decreased intake
༝ Obstructive jaundice
༝ Abetalipoproteinemia
༝ Cirrhosis of liver
༝ Severe malnutrition
༝ Chronic nephrosis
༝ Fat malabsorption,
༝ Acute & chronic infection
༝ Smoking
30
Vitamin A Deficiency
༝ kekurangan vitamin A telah dikaitkan dengan perlambatan re-
epitelisasi, penurunan sintesis dan stabilitas kolagen dan
peningkatan kerentanan terhadap infeksi.
༝Etiology of Vitamin A deficiency :
༝ Decreased intake
༝ Obstructive jaundice
༝ Abetalipoproteinemia
༝ Cirrhosis of liver
༝ Severe malnutrition
༝ Chronic nephrosis
༝ Fat malabsorption,
༝ Acute & chronic infection
༝ Smoking penyebab defisiensi hampir semua vitamin 31
Deficiency Manifestations of Vitamin A
༝ The deficiency manifestations are related to the eyes, skin and
growth.
2
Therapeutic Doses Vitamin A
༝ Vitamin A supplementation for eye disorders prevention
༝6 - 12 months blue capsule vitamin A (100,000 SI)
༝12 - 59 months red capsule vitamin A (200,000 SI)
༝ Therapeutic dose for eye disorders night blindness – corneal xerosis
༝1 day
st
34
Toxicity
༝ Asupan berlebihan menyebabkan keracunan.
༝ Preform vitamin A nutrisi penting yang berpotensi
menyebabkan toksisitas (yang berasal dari hewan)
༝ gejala keracunan mempengaruhi sistem saraf pusat, hati,
homeostasis kalsium, dan kulit.
༝ konsumsi beta karoten yang berlebihan dari sumber makanan
dapat menyebabkan kulit menguning tetapi tidak berbahaya
35
Toxicity
༝ Acute hypervitaminosis A
༝Adult : Retinol > 200 mg (660.000 IU/single dose)
༝Children : Retinol > 100 mg (330.000 IU/single dose)
36
Toxicity
༝ Acute hypervitaminosis A
༝Adult : Retinol > 200 mg (660.000 IU/single dose)
༝Children : Retinol > 100 mg (330.000 IU/single dose)
37
Interaction with Other Nutrients
༝ Vitamin A supplementation will lead to hematopoiesis state in
anemia (suplementasi vitamin A dalam dosis tinggi akan
menyebabkan keadaan hematopoiesis pada anemia)
38
Vitamin D
Overview
༝ Known as calciferol, 1,25-dihydroxy vitamin D
(calcitriol), vitamin D3 (Cholecalciferol), vitamin D2
(ergocalciferol)
༝ It is present in animals, plants & has several
important functions in the body.
༝ Considered as hormone
40
Overview
༝ dikenal sebagai kalsiferol, 1,25 – dihidroksi
vitamin D (kalsitriol), vitamin D3
(kolekalsiferol), vitamin D2 (ergokalsiferol).
༝ ada pada hewan, tumbuhan, dan memiliki fungsi
penting dalam tubuh
༝ dianggap sebagai hormone
41
༝ Vitamin D is derived from 7-dehydrocholesterol (ergosterol) by
the action of UV radiations.
༝ There are two chemical forms of vitamin D :
༝ Vitamin D2 (Ergocalciferol) - found in plants
༝ Vitamin D3 (Cholecalciferol) - found in animals
༝ Ergocalciferol and cholecalciferol are sources for vitamin D
activity and are referred to as provitamins.
༝ Transformation from inactive provitamin to the active vitamin is
accomplished by the ultraviolet rays.
42
༝ Vitamin D berasal dari 7-dehydrocholesterol (ergosterol) oleh
aksi radiasi UV. Dikenal sebagai sunshine vitamin
༝ There are two chemical forms of vitamin D /precursor vitamin D:
༝ Vitamin D2 (Ergocalciferol) - found in plants
༝ Vitamin D3 (Cholecalciferol) - found in animals
༝ Ergocalciferol and cholecalciferol merupakan sumber
aktivitas vitamin D dan disebut sebagai provitamin
༝ Tranformasi dari provitamin tidak atif menjadi vitamin aktif
dibantu oleh sinar ultraviolet
43
Metabolism & Biochemical Function of Vitamin D
44
Regulation of Vitamin D
༝ Regulation of calcitriol synthesis is done by:
༝ Its own concentration—by feedback inhibition of 1 α-hydroxylase
༝ Parathyroid hormone (PTH)
༝ Serum phosphate level
༝ PTH is released in low serum Ca and induces the production of
calcitriol
༝ Calcitriol regulates its own concentration, inhibit “1 α-hydroxylase”
and stimulates 24,25-di-OH-D3 (Secalcifediol) , which is inactive.
༝ Mode of action of calcitriol
༝ Calcitriol acts as a steroid hormone receptors.
༝ This binding is specific and reversible.
༝ The receptor has a specific binding site on DNA.
45
Regulation of Vitamin D
༝ pengaturan sintesis kalsitriol dilakukan dengan cara :
༝ konsentrasinya sendiri dengan inhibisi umpan balik dari 1 α-
hydroxylase
༝Parathyroid hormone (PTH)
༝kadar serum fosfat
47
Vitamin D Is Considered As A “Prohormone”
& Calcitriol (1,25-di-oh-d3)
AsA Hormone
• Seperti hormon, calcitriol memiliki organ "target" yang pasti seperti usus
kecil, tulang dan ginjal untuk ditindaklanjuti. Ini diproduksi di satu organ
dan bekerja pada organ target yang jauh untuk aktivitasnya (properti
hormon).
• Calcitriol menyerupai hormon steroid dalam cara kerjanya, yaitu
NUCLEAR ACTION.
• Kalsitriol mempertahankan homeostasis kalsium bersama dengan—dua
hormon protein lain parathormon (PTH) dan kalsitonin.
• Parathormon (PTH) dianggap sebagai hormon “tropic” untuk calcitriol, ia
meningkatkan produksi calcitriol dengan merangsang enzim “1 -
hidroksilase” di tubulus ginjal.
48
Action of Calcitriol on Calcium Homeostasis
49
Functions of Vitamin D
༝ Calcium and Phosphorus Homeostasis
༝ Calcium and Phosphorus absorption (small intestine)
༝ Calcium resorption (bone and kidney)
༝ Maintain blood calcium levels
༝ Bone formation
༝ Stimulate calcium uptake for deposition as calcium phosphate
(Osteoblasts: bone-forming cells)
༝ Hormone
༝ Regulation of gene expression
༝ Cell growth
50
Functions of Vitamin D
• Homeostasis Kalsium dan Fosfor
Penyerapan Kalsium dan Fosfor (usus halus)
Resorbsi kalsium (tulang dan ginjal)
Menjaga kadar kalsium darah
• Pembentukan tulang
Merangsang pengambilan kalsium untuk deposisi sebagai kalsium
fosfat (Osteoblas: sel pembentuk tulang)
• Hormon
Regulasi ekspresi gen
Pertumbuhan sel
51
Functions of Vitamin D
༝ Action of calcitriol on the intestine: Calcitriol increases the intestinal
absorption of calcium and phosphate.
༝ Action of calcitriol on the bone : In the osteoblast of bone, calcitriol
stimulate calcium uptake for deposition and calcium phosphate.
Calcitriol is essential for bone formation.
༝ Action of calcitriol on the kidney : Calcitriol is also involved in
minimizing the excretion of calcium and phosphate through the kidney,
by decreasing their excretion and enhancing reabsorption.
52
Functions of Vitamin D
• kerja calcitriol pada usus: Calcitriol meningkatkan penyerapan
kalsium dan fosfat usus.
• Kerja kalsitriol pada tulang : Dalam osteoblas tulang, kalsitriol
merangsang pengambilan kalsium untuk deposisi dan kalsium fosfat.
Kalsitriol sangat penting untuk pembentukan tulang.
• kerja calcitriol pada ginjal : Calcitriol juga terlibat dalam
meminimalkan ekskresi kalsium dan fosfat melalui ginjal, dengan
menurunkan ekskresi dan meningkatkan reabsorbsi.
53
RDA of Vitamin D
༝ The daily requirement of vitamin D is expressed as microgram or IU
༝ 1 µg of vitamin D = 40 International Units
༝ Children : 10µg/day (400 IU)/day
༝ Adults : 5-10 μg/ day (200IU)/day
༝ Pregnancy and lactation : 10µg/day
༝ Over 70years : 600 IU/day
54
RDA of Vitamin D
Age Groups Vitamin D Age Groups Vitamin D Age Groups Vitamin D
(mcg) (mcg) (mcg)
Infant & Children
• 0 – 6 months • 5 mcg
• 7 – 11 months • 5 mcg Female Male
• 1 – 3 years • 15 mcg • 10 – 12 years • 15 mcg • 10 – 12 years • 15 mcg
• 4 – 6 years • 15 mcg • 13 – 15 years • 15 mcg • 13 – 15 years • 15 mcg
• 7 – 9 years • 15 mcg • 16 – 18 years • 15 mcg • 16 – 18 years • 15 mcg
• 19 – 29 years • 15 mcg • 19 – 29 years • 15 mcg
Pregnant
• TM 1 • 30 – 49 years • 15 mcg • 30 – 49 years • 15 mcg
• no add
• TM 2 • 50 – 64 years • 15 mcg • 50 – 64 years • 15 mcg
• no add
• TM 3 • 65 – 80 years • 20 mcg • 65 – 80 years • 20 mcg
• no add
• > 80 years • 20 mcg • > 80 years • 20 mcg
Breastfeed • no add
55
Functions of Vitamin D
56
Deficiency of Vitamin D
Concentration of Vitamin D level (ng/ml)
༝Normal level of vitamin D : 30 ng/ml
༝Vitamin D insufficiency : 20 - 29 ng/ml
༝ Vitamin D deficiency : 10 - 19 ng/ml
༝ Severe deficiency : < 10 ng/ml
༝ Toxicity : > 150ng/ml
57
Deficiency of Vitamin D
Causes for Vitamin D Deficiency
༝People who are not exposed to sunlight properly.
༝ Nutritional deficiency of calcium or phosphate
༝ Malabsorption of vitamin (obstructive jaundice and steatorrhea) and high
phytate content in diet reduce the absorption of vitamin.
༝ Deficient renal absorption of phosphates
༝ Certain disease such as SLE (Systemic Lupus Erythematosus),
immobilization, melanoma
༝ Application of sunscreen lotions or presence of dark skin color decrease
this synthesis
58
Deficiency of Vitamin D
Causes for Vitamin D Deficiency
• Orang yang tidak terkena sinar matahari dengan baik.
• Kekurangan nutrisi kalsium atau fosfat
• Malabsorbsi vitamin (ikterus obstruktif dan steatorrhea) dan tinggi
Kandungan fitat dalam makanan mengurangi penyerapan vitamin.
• Defisiensi absorpsi fosfat oleh ginjal
• Penyakit tertentu seperti SLE (Systemic Lupus Erythematosus), imobilisasi,
melanoma
• Aplikasi lotion sunscreen atau adanya warna kulit gelap menurunkan sintesis
ini
• Kondisi autoimun
59
Deficiency of Vitamin D
༝ Childrean rickets
༝ Adults osteomalacia
༝ Others :
༝ osteoporosis, diabetes, cancer (colon, breast, ovarium, prostate)
autoimun disease (asthma, rheumatoid arthritis, multiple sclerosis,
psoriasis),proximal myophaty, cardiovascular disease, hypertension,
etc
60
Hypervitaminosis D
༝ Hypervitaminosis D
༝ Among the vitamins, vitamin D is the most toxic in
overdoses(10-100 times RDA)
༝ Calcification of soft tissue
༝ Lungs, heart, blood vessels
༝ Hardening of arteries, stone formation in kidneys
༝ Does not occur from sunlight or dietary sources
༝ Does occur with supplementation
༝ In general, vitamin D supplement are not recommended.
༝ Upper limit: 50 micrograms a day
61
Hypervitaminosis D
༝Hypervitaminosis D
༝ diantara vitamin, vitamin D adalah yang paling
beracun ketika overdosis (10-100 kali RDA)
༝klasifikasi jaringan lunak
༝paru-paru, jantung, pembuluh darah
༝pengerasan pembukuh darah, pembentukan batu di
ginjal
༝ tidak terjadi dari sinar matahari atau sumber
makanan tetapi terjadi karena pemberian
suplementasi dosis besae
༝ secara umum, suplemen vitamin D tidak dianjurkan.
༝ batas atas: 50 microgram sehari
62
Hypervitaminosis D
Toxic effects of hypervitaminosis D include
༝ Doses above 10,000IU/day for long period causes toxicity.
༝ Demineralization of bone (resorption) and increased calcium
absorption from the intestine, leading to elevated calcium in
plasma (hypercalcemia).
༝ Prolonged hypercalcemia is associated with deposition of
calcium in many soft tissues such as kidney and arteries.
༝ Formation of stones in kidneys (renal calculi).
༝ Symptoms include weakness, polyuria, intense thirst, difficulty
in speaking, hypertension, loss of appetite, loss of weight etc.
63
Hypervitaminosis D
Toxic effects of hypervitaminosis D include
༝ Dosis di atas 10,000IU/hari dalam jangka waktu lama
menyebabkan toksisitas
༝ demineralissi tulang (resorpsi) dan peningkatan penyerapan
kalsium dari usus, menyebabkan peningkatan kalsium dalam
plasma (hiperkalsemia)
༝ hiperkalsemia yang berkepanjangan berhubungan
dengan deposisi kalsium di banyak jaringan lunak
seperti ginjal dan arteri.
༝ pembentukan batu pada ginjal (renal calculi)
༝ gejala termasuk kelemahan, polyuria, rasa haus yang
intens, kesulitan berbicara, hipertensi, kehilangan nafsu
makan, penurunan berat badan, dll
64
Vitamin E
Overview
༝ Naturally occurring anti-oxidant.
༝ Evans & Bishop(1936) - isolated active vitamin.
༝ Named – Tocopherol.
༝ (Tokos :childbirth, pherein: to bring ,ol :alcohol)
༝ Anti-sterility vitamin- Essential for normal reproduction in
many animals.
46
Overview
༝ anti oksidan alami
༝ Evans & Bishop(1936) – vitamin aktif yang diisolasi.
༝ bernama – Tocopherol.
༝ (Tokos :childbirth, pherein: to bring ,ol :alcohol)
༝ Anti-sterility vitamin- penting untuk reproduksi normal
pada kebanyakan hewan
• Berperan dalam pencegahan penyakit cancer dan
jantung
46
Chemistry of Vitamin E
༝ Elucidated by Paul Karrer, awarded Nobel Prize in 1937.
༝ Name given to a group of tocopherols & tocotrienols.
༝ About eight tocopherols have been identified- α, β, γ, δ etc.
༝ α-tocopherol is the most active.
༝ Derivatives of 6-hydroxy chromane (tocol) ring with
isoprenoid side chain.
༝ antioxidant property is due to the chromane ring.
α-tocopherol 47
Chemistry of Vitamin E
• Dijelaskan oleh Paul Karrer, dianugerahi Hadiah Nobel
pada tahun 1937.
• Nama yang diberikan untuk kelompok tokoferol &
tokotrienol.
• Sekitar delapan tokoferol telah diidentifikasi- α, β, γ, δ e
dll.
• α-tokoferol adalah yang paling aktif.
• Derivatif dari cincin 6-hidroksi kromana (tokol) dengan
rantai samping isoprenoid.
• sifat antioksidan karena memiliki cincin chromane.
α-tocopherol 47
Chromanol ring
Isoprenoid chain Isoprenoid chain
V
i
t
a
m
e
r
70
Absorption, Transportation & Storage
༝ Normal plasma level of tocopherol - 0.5-1mg/dl.
༝ Absorbed along with fat in Small intestine.
༝ Bile salts is necessary.
༝ Absorbed and transported as chylomicrons.
༝ In liver, incorporated in Lipoproteins & transported.
༝ Stored in adipose tissue.
༝ During catabolism, chromane ring & side chain may be
oxidized.
༝ Excreted in bile- conjugation with glucuronic acid,
urine and skin
71
Absorption, Transportation & Storage
• Kadar tokoferol plasma normal - 0,5-1mg/dl.
• Diserap bersama lemak di usus halus.
• Garam empedu diperlukan.
• Diserap dan diangkut sebagai kilomikron.
• Di hati, tergabung dalam Lipoprotein & diangkut.
• Disimpan dalam jaringan adiposa.
• Selama katabolisme, cincin kroman & rantai samping
isoprenoid mungkin teroksidasi.
• Diekskresikan dalam empedu-konjugasi dengan asam
glukuronat, urin dan keringat/kulit
72
Major Functions of Vitamin E in the Body
༝ Antioxidant
༝Vitamin E is very unstable, easily oxidized
༝protect cells against oxidative damage by free radicals, for example
oxidation of the lipids in the cell membranes
༝ plays a role in aging, sexual performance, or prevention of
cancer and/or heart disease
73
Major Functions of Vitamin E in the Body
• Antioksidan
• Vitamin E sangat tidak stabil, mudah teroksidasi
• melindungi sel terhadap kerusakan oksidatif oleh radikal
bebas, misalnya oksidasi lipid/lemak pada membran sel
• berperan dalam penuaan, kinerja seksual/kesuburan, atau
pencegahan kanker dan/atau penyakit jantung
74
Functions of Vitamin E
༝ Powerful Antioxidant- Essential for the membrane structure and integrity
of the cell.
༝Free radicals scavenger- Protects RBC from hemolysis.
༝ Slow down aging process and boost Immune response.
༝ Protects LDL from oxidation - Reduces the risk of atherosclerosis.
༝ Associated with reproductive functions and prevents sterility.
༝ Prevent chronic diseases such as cancer and heart disease.
༝ Protects liver from being damaged by toxic compounds.
༝ Required for Proper Hair Growth (Beauty Vitamin along with BIOTIN)
75
Functions of Vitamin E
• Antioksidan Kuat- Penting untuk struktur membran dan integritas
sel.
• Pelindung radikal bebas- Melindungi sel darah merah dari
hemolisis.
• Memperlambat proses penuaan dan meningkatkan respon imun.
• Melindungi LDL dari oksidasi - Mengurangi risiko aterosklerosis.
• Berhubungan dengan fungsi reproduksi dan mencegah
kemandulan.
• Mencegah penyakit kronis seperti kanker dan penyakit jantung.
• Melindungi hati dari kerusakan oleh senyawa beracun.
• Diperlukan untuk Pertumbuhan Rambut yang Tepat (Vitamin
Kecantikan bersama dengan BIOTIN)
76
RDA of Vitamin E
༝ Males – 10mg/day.
༝ Females – 8mg/day.
༝ Pregnancy - 10mg/day.
༝ Lactation- 12mg/day.
༝ 15 mg vitamin E = 33 IU
༝ Pharmacological dose = 200-400 IU/day.
77
RDA of Vitamin E
Age Groups Vitamin E Age Groups Vitamin E Age Groups Vitamin E
(mg) (mg) (mg)
Infant & Children
• 0 – 6 months • 4 mg
• 7 – 11 months • 5 mg Female Male
• 1 – 3 years • 6 mg • 10 – 12 years • 11 mg • 10 – 12 years • 11 mg
• 4 – 6 years • 7 mg • 13 – 15 years • 15 mg • 13 – 15 years • 12 mg
• 7 – 9 years • 7 mg • 16 – 18 years • 15 mg • 16 – 18 years • 15 mg
• 19 – 29 years • 15 mg • 19 – 29 years • 15 mg
Pregnant
• TM 1 • 30 – 49 years • 15 mg • 30 – 49 years • 15 mg
• no add
• TM 2 • 50 – 64 years • 15 mg • 50 – 64 years • 15 mg
• no add
• TM 3 • 65 – 80 years • 15 mg • 65 – 80 years • 15 mg
• no add
• > 80 years • 15 mg • > 80 years • 15 mg
Breastfeed • add 4 mg
• add 4 mg
78
Dietary Sources of Vitamin E
Richest source
༝ Vegetable oils – Wheat Germ Oil, Sunflower Oil, Cotton Seed Oil,
Olive oil.
༝Coconut oils – relatively low.
༝ Fish liver oils – devoid.
79
Vitamin E Deficiency Manifestations
༝ Rarely happened
༝ Major Symptoms :
༝Erythrocyte hemolysis and hemolytic anemia, disruption of red
blood cell membranes, perhaps due to polyunsaturated fatty
acids (PUFAs) oxidation
༝Hemolytic anemia – increased red blood cell fragility
༝Acute hepatic necrosis- Diets low in cystine and rich in
polyunsaturated fatty acids can cause hepatic necrosis
༝Muscular dystrophy- Muscular weakness & creatinuria.
༝Sterility: reproductive failure
80
Vitamin E Deficiency Manifestations
• Jarang terjadi
• Gejala Utama :
• Hemolisis eritrosit dan anemia hemolitik, gangguan membran sel
darah merah, mungkin karena lemak tak jenuh ganda oksidasi
asam (PUFAs)
• Anemia hemolitik – peningkatan kerapuhan sel darah merah
• Nekrosis hati akut- Diet rendah sistein dan kaya asam lemak tak
jenuh ganda (PUFA) dapat menyebabkan nekrosis hati
• Distrofi otot- Kelemahan otot & kreatininuria.
• Kemandulan: kegagalan reproduksi
81
Hypervitaminosis E
༝ Toxicity rare: wide range of safe intake compared to other
fat soluble vitamins
༝ Vitamin E is one of the most popular nutrient supplements.
There are many health claims for supplementation –
slowing of the aging process or an improvement in sexual
potency.
Doses above 1000 IU/day, cause –
༝ Tendency of hemorrhage, as it is a mild anti-coagulant.
༝ Minor Neurological symptoms..
82
Hypervitaminosis E
• Toksisitas langka: berbagai asupan aman dibandingkan
dengan vitamin larut lemak lainnya
• Vitamin E adalah salah satu suplemen nutrisi yang paling
populer.
Ada banyak klaim kesehatan untuk suplementasi –
memperlambat proses penuaan atau peningkatan potensi
seksual/fungsi reproduksi.
Dosis di atas 1000 IU/hari, menyebabkan Kecenderungan
perdarahan, karena merupakan antikoagulan ringan.
• Gejala Neurologis Kecil..
83
Vitamin K
Overview
༝ Vitamin K is the only fat soluble vitamin with a specific coenzyme
function.
༝ Produce by intestinal bacteria
༝ Required for the production of blood clotting factors, essential for
coagulation. Named as antihemorrhagic vitamin.
༝ Naphthoquinone derivatives, with a long isoprenoid side chain.
85
Overview
• Vitamin K adalah satu-satunya vitamin yang larut dalam
lemak dengan fungsi koenzim tertentu.
• Diproduksi oleh bakteri usus
• Diperlukan untuk produksi faktor pembekuan darah, penting
untuk pembekuan. Dinamakan sebagai vitamin
antihemoragik.
• Turunan naptokuinon, dengan rantai samping isoprenoid yang
panjang.
86
Chemistry of Vitamin K
Exists in different forms –
༝ Vitamin K1 - Phylloquinone
༝ present in plants
༝ has 20C chain
༝ Vitamin K2 - Menaquinone
༝ present in animal
༝ produced by intestinal bacteria
༝ has 30C chain
༝ Vitamin K3 - Menadione
༝ water soluble synthetic form,
༝ complexed to improve stability
༝ no side chain
87
Absorption, Transportation & Excretion of
Vitamin K
༝ Absorption occurs in the intestine in the presence of bile salts.
༝ The transportation from intestine is carried out through
chylomicrons.
༝ Storage occur in liver and from liver transportation to peripheral
cells is carried out bound with beta lipoproteins.
༝ Excretion primarily through bile, small amount urine
88
Absorption, Transportation & Excretion of
Vitamin K
• Penyerapan terjadi di usus halus dengan adanya garam
empedu.
• Transportasi dari usus halus diangkut oleh kilomikron.
• Penyimpanan terjadi di hati dan dari transportasi hati ke organ
lain dibantu perifer sel dilakukan terikat dengan beta
lipoprotein.
• Ekskresi terutama melalui empedu, urin dalam jumlah sedikit
89
Functions of Vitamin K
༝ Necessary for coagulation
༝Factors depended are :
༝ Factor II
༝ Factor VII
Synthesized by Liver as Zymogens
༝ Factor IX
༝ Factor X
༝It brings about the post-translational modification. (membawa
tentang modifikasi pasca-translasi)
༝Vitamin K is converted to hydroquinone in liver by dehydrogenase
using NADPH then acts as a coenzyme for the carboxylation of
glutamic acid residue, catalysed by a carboxylase. (vitamin K
diubah menjadi hidrokuinon di hati oleh dehydrogenase
menggunakan NADPH kemudian bertindak sebagai koenzim
untuk karboksilasi residu asam glutamate, dikatalisis oleh
karboksilase) 90
Functions of Vitamin K
༝ Calcium binding protein
༝Vitamin K dependent gamma
carboxylation necessary for
osteocalcin, structural protein of
Kidney, lung and spleen.
༝ Stimulates bone formation and
decreases bone resorption.
༝ γ-carboxyglutamate is inhibited by
dicoumarol, an anticoagulant.
93
Role of Vitamin K in Clotting
• Faktor pembekuan disintesis di hati sebagai prekursor tidak aktif -
vitamin K mengubahnya menjadi bentuk aktifnya
• Residu asam karboksiglutamat (Gla) bermuatan negative (COO-) dan
mereka bergabung dengan ion kalsium bermuatan positif (Ca2+)
untuk membentuk kompleks.
• Kompleks protrombin-Ca berikatan dengan fosfolipid pada
permukaan membran trombosit.
• Menyebabkan peningkatan konversi protrombin menjadi trombin,
enzim aktif
• Pembentukan fibrinogen menjadi fibrin berperan dalam proses
pembekuan darah
94
Dietary Sources of Vitamin K
༝ Green leafy vegetables are good dietary sources.
༝ Vitamin K is present in vegetable oils and is particularly rich in
olive, canola, and soybean oils.
༝ Some amount is contributed by intestinal bacteria
95
96
RDA of Vitamin K
༝ The recommended daily allowance (RDA) is 50-100 mg/day
༝ Available in normal diet.
༝ Requirement increases in (peningkatakn kebutuhanketika) :
༝ Liver disorders
༝Patients on prolonged antibiotic therapy, bile acid sequestrants. (pasien
dengan terapi antibiotic berkepanjangan, sekuestran asam empedu)
97
RDA of Vitamin K
Age Groups Vitamin K Age Groups Vitamin K Age Groups Vitamin K
(mcg) (mcg) (mcg)
Infant & Children
• 0 – 6 months • 5 mcg
• 7 – 11 months • 10 mcg Female Male
• 1 – 3 years • 15 mcg • 10 – 12 years • 35 mcg • 10 – 12 years • 35 mcg
• 4 – 6 years • 20 mcg • 13 – 15 years • 55 mcg • 13 – 15 years • 55 mcg
• 7 – 9 years • 25 mcg • 16 – 18 years • 55 mcg • 16 – 18 years • 55 mcg
• 19 – 29 years • 55 mcg • 19 – 29 years • 65 mcg
Pregnant
• TM 1 • 30 – 49 years • 55 mcg • 30 – 49 years • 65 mcg
• no add
• TM 2 • 50 – 64 years • 55 mcg • 50 – 64 years • 65 mcg
• no add
• TM 3 • 65 – 80 years • 55 mcg • 65 – 80 years • 65 mcg
• no add
• > 80 years • 55 mcg • > 80 years • 65 mcg
Breastfeed • no add
• no add
98
Deficiency of Vitamin K
༝ Deficiency: increased bleeding and hemorrhage
༝ rare, they may occur in some individuals when antibiotic
medications kill the intestinal bacteria that produce the vitamin.
༝ Vitamin K deficiency are common in newborns. Parenteral
treatment with vitamin K is recommended at birth.
99
Deficiency of Vitamin K
• Defisiensi: peningkatan perdarahan jarang, mereka dapat
terjadi pada beberapa individu ketika obat antibiotik
membunuh bakteri usus yang menghasilkan vitamin.
• Kekurangan vitamin K sering terjadi pada bayi baru lahir.
Diatasi dengan pemberian vitamin K secara Parenteral
• pengobatan dengan vitamin K dianjurkan saat lahir.
10
Deficiency of Vitamin K
༝ Prolonged use of antibiotics and sulfa drugs
༝ Malabsorption and biliary tract obstruction
༝ In immediate post-natal infants Hypoprothrombinemia and
bleeding occurs in vitamin K deficiency
༝ Fetal Warfarin syndrom
• Penggunaan antibiotik dan obat sulfa dalam waktu lama
• Malabsorbsi dan obstruksi saluran empedu (ikterik)
• Pada bayi segera setelah lahir Hipoprotrombinemia dan
perdarahan terjadi pada defisiensi vitamin K
• Sindrom Warfarin Janin adanya paparan terhadap warfarin.
Ibu mengonsumsi obat-obatan dengan kandungan warfarin,
kemudian warfarin terdesposisi ke dalam janin 10
Causes for Vitamin K Deficiency
༝ Decreased intake.
༝ Malabsorption of lipids-
༝Results from obstructive Jaundice, chronic pancreatitis, sprue, etc.
༝ Prolonged antibiotic therapy and gastrointestinal infections with
diarrhea.
༝ Treatment of pregnant women with warfarin can lead to fetal
bone abnormalities.
༝ Prolongation of prothrombin time and delayed clotting time, is
vitamin K deficiency.
10
Causes for Vitamin K Deficiency
• Penurunan asupan.
• Malabsorbsi lipid
• Hasil dari penyakit kuning obstruktif, pankreatitis kronis,
sariawan, dll.
• Terapi antibiotik berkepanjangan dan infeksi gastrointestinal
dengan diare.
• Pengobatan ibu hamil dengan warfarin dapat menyebabkan
kelainan tulang janin.
• Perpanjangan waktu protrombin dan penundaan waktu
pembekuan, adalah kekurangan vitamin K.
10
Hypervitaminosis K
༝ The toxic effect is due to increased breakdown of RBC.
༝ Large quantities of menadione result in toxicity.
༝ Hypervitaminosis K:
༝ Thrombosis,
༝ Hemolytic anaemia
༝ Hemolysis
༝ Hyperbilirubinemia Jaundice, particularly in infants.
༝ Kernicterus and brain damage
10
Hypervitaminosis K
• Efek toksik disebabkan oleh peningkatan pemecahan sel darah
merah.
• Hipervitaminosis K:
• Trombosis,
• Anemia hemolitik
10
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10
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10
Water-Soluble Vitamins
Nutrition Biochemis try
2021
Dian Luthfita Prasetya Muninggar
Nutrition Department
Politeknik Kesehatan Kemenkes Semarang
Recommended Dietary Allowance
2
Vitamin B1 (Thiamine)
6
Metabolism
༝ Thiamine (from food) is absorbed in the duodenum and
jejunum through active transport and carrier-mediated
system diffussion
༝ Limited storage in the liver, could disappear within 12-14 days
༝ Excretion through urine
༝ As a precursor of TPP, which is catalyzed by the enzyme
thiamin pyrophosphotrans feras e, it requires ATP, in the liver,
and muscle, brain, heart, and reticulocyte.
7
Deficiency
Dry beriberi Wet beriberi
༝ weakness ༝ edema
༝ nerve degeneration ༝ heart enlargement
༝ irritability ༝ heart failure
༝ lack of hand / foot
coordination
༝ damage
trans mis s ion to the
nervous system
8
Risk of Deficiency
༝ Low socio-economic
༝ Alcoholic
༝ Elderly
༝ Frequently consumed packaged food
9
Thiamine Assessment
༝ Thiamine excretion in urine
༝ Thiamine concentration in the blood / serun
༝ Erythrocyte transketolase activity
༝ Activation of apo-transketolase which are contained in erythrocyte
lysis products by the addition of thiamine diphosphate in vitro has
been used as a thiamine status index.
10
Riboflavin (Vitamin B2)
isoalocsazine ring with a ribbon side chain
Overview
༝ Characteris tics : ea sily des troyed by UV rays and alkaline
conditions, heat resistence; required special treatment for
assessm ent & packaging of food products
༝ Acts as the components of coenzyme flavin FMN (flavin
mononucleotide) and FAD (flavin adenine dinucleotide)
༝ Acts as an electron acceptor
༝ Has a central function in energy production and cellular
respiration.
༝ A catalytic coenzyme in glucose & fatty acids metabolism
12
13
Components of the respiratory chain in mitochondria
*coenzyme for oxidation - reduction reactions in cellular respiration process 14
Metabolism
༝ Absorption in the intestine simultaneously with phosphorylation in
the intestinal mucosa to form F M N
༝ Maximum absorption occurs in jejenum
༝ Converted into FAD in liver
༝ Riboflavin deposited in the form of FAD (70-90%), but immediately
used again so its daily intake is needed
༝ The excess will be excreted through urine
15
Sources
༝ Milk ༝ Heart
༝ Meat
༝ Egg
༝ Green vegetables (sayuran berdaun hijau)
Jeroan
༝ animal sources are more easily absorbed than vegetable
(paling mudah diserap berasal dr hewani)
16
Deficiency
Ariboflavinosis:
༝ Glossitis, cheilosis, seborrheic dermatitis, stomatitis, eye &
throat disorders, nervous system disorders
17
Risk of Deficiency (Resiko Defisiensi)
༝ Rarely happened (jarang tjd)
༝ Lack of dairy intake and its products
༝ Alcoholic
༝ Long-term use of phenobarbital flavokinase inhibitors
18
Niacin : Nicotinic
acid (Vitamin
B3)
Contains acid and amide forms
Overview
༝ Known as nicotinamide or nicotinic acid
༝ Nicotinic Acid = Niacin
༝ Nicotinamide = Niacinamide
༝ Derivatives from pyridine, the non-toxic part of the tobacco
nicotine alkaloid
༝ Main element of NAD + and NADP (Nicotinamide
dinucleotide phosphate)
༝ Not easily destroyed by high temperatures, UV lights,
acids, alkalis and oxidation
༝ Not easily damaged by normal processing and cooking.
20
Functions
༝ Coenzyme :
༝ Nicotinamide adenine dinucleotide (NAD) Glycogen synthesis
& DNA r epair
༝ Nicotinamide adenine dinucleotide phosphate (NADP)
༝ Redox reactions which involved in
༝ glycolysis,
༝ fatty acid metabolis m,
༝ tissue respiration,
༝ detoxification
21
Metabolism
༝ Absorption in the small intestine as nicotinic acid,
nicotinamide and nicotinamide mononucleotides (NMN),
through simple & facilitated diffusion.
༝ Available in circulation in free form of niacin.
༝ Free Niacin which are not converted into NAD and NADP,
are further metabolized and excreted in urine
༝ Niacin also could be synthesized from tryptophan, but it’s
not efficient, because it requires 60 mg of tryptophan to
produce 1 mg of niacin; and also requires vitamins B1, B2
and B6
22
Sources
༝ Mushroom (jamur)
༝ Grains biji”an
༝ Meat, fish Ikan, daging
༝ Corn poor niacin and tryptophan
Jagung > kadar niasin dan triptofan
rendah
23
Deficiency
Pellagra
༝ characterized by symptoms of depression, photosensitive
dermatitis and diarrhea
24
Niacin Assessment
༝ Urinary excretion from niacin metabolites : N-methyl
nicotinamide
༝ Niacin I s Toxic in Excess
༝ Increase histamine release: dilation and flushing of blood
vessels, with skin irritation
༝ Cause liver damage : an excess of 500mg / dl of nicotinic and
nicotinamide acid intake
༝ At doses> 2500mg / day, niacin can cause hypotension,
dizziness, increased uric acid, liver disorders, increased risk of
stomach ulcers and increased blood glucose levels.
25
Pantothenic Acid
Known as vitamin B3, which consist of β-alanine &
panthoic acid
Functions
༝ Part of Coenzyme-A acts as the carrier of the acyl group
༝ Essential for carbohydrate, fat & protein metabolism
༝ fatty acid metabolis m
༝ carbohydrate metabolism (citric acid cycle and gluconeogenesis)
༝ synthesis of acetylcholine, steroid hormones, cholesterol, and
phospholipids
༝ porphyrins synthesis, which are needed for the formation of
hemoglobin
27
Metabolism
༝ Consumed as part of coenzymeA, in gastrointestinal tract
hydrolyzed to 4-phosphopantein and pantothenic acid
༝Absorption through facilitated diffusion.
༝ CoA is synthesized again in liver cells.
༝ Circulates in erythrocytes and plasma.
༝ Excretion through urine
༝ Stored in erythrocytes and lipid cells.
28
Sources
༝ Fres h Vegetables
༝ Seeds & Nuts
༝ Milk, Egg, Meat
Sayuran segar,
biji”an dan
kacang”an, susu,
daging, telur
29
Deficiency
༝ Rarely occurs, usually in combination with other vitamin B
deficiencies
༝ Burning foot syndrome, fatigue, headache, sleep disturbance,
nausea, abdominal distress
༝ Alcoholics are at risk
30
Vitamin B6
Metabolism
༝ Passive absorption in the intestine
༝ The three forms of vit B-6 will be phosphorylated by the
enzyme pyridoxal kinase, in the liver, brain and kidneys
༝ Could be stored in the liver, brain and skeletal muscles
༝ Urinary excretion in the form of pyridoxic acid.
32
Functions
༝ Coenzymes: PLP, P M P
༝ Transamination, decarboxylation, deamination,
and racemization reactions are needed
༝ Coenzymes for glycogen phosphorylation
33
Functions
༝ PLP helps the processes that produce
neurotransmitters: epinephrine, norepinephrine,
dopamine, serotonin and GABA
༝ PLP forms hem precursors in hemoglobin.
༝ PLP is needed to convert tryptophan to niacin.
༝ PLP is involved in the transformation of linoleic
acid into arachidonic acid
༝ PLP is important in the formation of nerve cell
myelin layers.
༝ Pyridoxine plays an important role in cell growth
and division.
34
Sources
༝ Seeds
༝ Grains
༝ Liver
༝ Egg
༝ Dairy
༝ Fresh green vegetables
༝ Toxicity can occur at a dose of 25 mg / day
༝ Symptoms: tingling in the legs, numbness in the hands;
body cannot function properly
35
Deficiency
༝ Microcytic hypochromic anemia
༝ Seborrheic dermatitis
༝ Convulsion, depression, confusion
༝ Reduce immune response
༝ Peripheral nerve damage
Who is at risk?
༝ Elderly
༝ TBC Therapy (isoniazid pyridoxal-hidrazon)
༝ Alcoholics alcohol decreases absorption, destroy the
coenzyme for m 36
Vitamin B12 (Cobalamin)
Overview
༝ The structure consists of porphyrin-like rings
such as hem, containing cobalt, linked to ribose
and phosphoric acid
38
Sources
༝ Meat
༝ Dairy
༝ Fish
༝ Synthesis products from gut microbacteria
༝ Not available in plants
39
Metabolism & Absorption
40
Functions
as Coenxyme 3 ‘-deoxi-adenosil-cobalamin
༝ which is important to change methyl-malonyl-CoA to succinyl-CoA, a
member of CAS or for raw materials porphyrin synthesis.
Help Trans-Metilation Reactions : METHYLCOBALAMIN
༝ the process of transferring methyl groups from TetraHidroFolicAcid to
homocysteine to methionine.
41
Functions
༝ Vit B12 is needed to activate folic acid
༝ Vit B12 is needed for all cells ’ normal functioning, in
digestive tract, bone marrow and nerve tissue.
༝ cofactor of 2 types of enzymes; methionine synthetase
methylalonil coA mutase.
42
Deficiency
megaloblastic anemia
༝ Methyl-folate trap
༝ Delayed or failure of normal cell division due to impaired
DNA s ynthes is
neuropathy
༝ defective myelination
༝ progressive peripheral weakening
43
Risk of Deficiency
༝ Vegetarian
༝ Babies who are breastfed by vegetarians
༝ Elderly
44
Folic Acids
(PTEROYGLUTAM IC ACID)
Overview
༝ Folacin is the general terms for folic acid & all compound
which have activities like acid folates
༝ Folate acid contains the pteridin which bonds p-
aminobenzoic acid (PABA) & glutamate
༝ Animals cannot synthesis of PABA or bind glutamate in
pteriuc acid, so it nedds folate from diets
46
Functions
Coenzyme: tetrahydofolate (THF)
༝ THF is important in the transfer reaction / carrying 1
carbon atom in the form of methyl, methilene, formimino,
formyl, methenil
༝ Important in the synthesis of serine, methionine, glycine,
purines, pyrimidines
༝ Required in pregnant women increased blood cell
proliferation; esp. in the first trimester
47
Tetrahydrofolic acid and the one-carbon substituted folates
48
49
Sources
༝ Yeast
༝ Liver
༝ Meat
༝ Fres h Vegetables (es p. as paragus )
༝ Fruits
༝ Whole grains
༝ Nuts
50
Metabolism
༝ Intes tinal Cells
༝ folate reduced to tetrahydrofolate by folate reductase,
inhibited by methotrexate (chemotheraputic drug)
༝ methylated to N5-methyl-THF; primary blood form
51
Deficiency
༝ Megaloblastic Anemia
༝ Neural tube defect
52
Megaloblastic Anemia
53
Neural Tube Defects
༝ Congenital defects which arise due to imperfect
closure of the neural tube
༝ Spina bifida
༝ Anencephaly
༝ Important to maintain folate intake prior and during
pregnancy
54
Biotin
Carboxylic acid which consist of an imidazole ring
and a tetrahydrotiophene ring with valeric acid
side chains
O
HN NH
HC CH
H2C CH-(CH2)4COOH
S
Sources
༝ Most of Gut flora products
༝ Corn
༝ Soybean
༝ Meat
༝ Fish
༝ Egg yolks
༝ Tomato
58
Deficiency
༝ Rarely occurs
༝ Except when there is an interuption of absorption or utilization
antibiotic for long terms
59
Vitamin C
Physiologically active forms for vitamin C
Overview
༝ It is water-soluble vitamin, commonly found in fruits and
vegetables.
༝ Vitamin C also known as ascorbic acid or ascorbate.
༝ Most animals are able to synthesize all vitamin C they
need from dietary sugars
༝ Also, animals are able to increase synthesis of vitamin C
during stress but humans’ strictly depend on dietary
sources, increases risk of deficiency during stress time.
༝ Human being is one of the few mammals unable to
synthesize vitamin C.
༝ Other animals unable to synthesize vitamin C include
primates, fruit bats, guinea pigs, and some birds.
61
༝ The problems related vitamin C referred to as scurvy
and associated with the lack of vitamin C had been quite
prevalent for centuries.
1 2 3
62
“
S curvy was common
between sailors,pirattes,
and others who were
onships
months without forfresh
eating
fruits and vegetables.
63
༝ Vitamin C was isolated in 1928, and its structure &
metabolism was determined in 1933 through uronic acid
pathways.
• although but humans do not have an ability to synthesize
vitamin C eventhough they also have uronic acid pathways
• The inability to synthesize vitamin C results from the lack of
gulonolactone oxidase, the last enzyme in the vitamin C
synthetic pathway.
64
Chemistry & Stability of Vitamin C
༝ It is a weak acid and its salts called ascorbate.
༝ Uns table in alkaline pH, high temperature, and in the
presence of oxygen or metals.
༝ Ascorbic acid is strong reducing agent, serves as an anti-
oxidant and co-factor in hydroxylation reactions.
༝ Ascorbic acid is reversibly oxidized to L- dehydroascorbic
acid and both L-ascorbic and L-dehydroascorbic acids are
physiologically active forms for vitamin C.
65
༝ Vitamin C have a number of vitamers that have vitamin C
activity in animals:
༝ Ascorbic acid in biological system (low pH)
༝ Oxidized form deyhroascorbic acid.
༝ Ascorbate in neutral salt solution (pH>5)
༝ Ascorbate and ascorbic acid are both naturally present in the
body, since the forms interconvert according to pH.
66
Sensitivity of Vitamin C
༝ Very significant losses occur as vegetables wilt, or when
they are cut, as a result of the release of ascorbate
oxidase from the plant tissue.
༝ Significant losses of the vitamin also occur in cooking, both
through leaching into the cooking water and also
atmospheric oxidation, which continues when foods are
left to s tand before s erving.
67
Natural Source of Vitamin C
Guava Orange Lemon
.
68
Natural Source of Vitamin C
Plum Red Pepper Papaya
.
Kiwi Broccoli
.
69
Sources of Vitamin C
༝ Fruits, vegetables and organ meats (liver, kidney).
༝ The best food sources of vitamin C include asparagus,
papaya, oranges, cantaloupe, cauliflower, broccoli, green
peppers, grapefruit, grapefruit, lemons, and strawberries.
༝ Citrus products are most commonly cited as significant
sources of the vitamin.
༝ Supplements supply vitamin C typically as free ascorbic
acid, calcium ascorbate, sodium ascorbate, and ascorbyl
palmitate.
70
Digestion, Absorption & Transport of Vitamin C
༝ Does not require digestion prior to being absorbed into intestinal cells.
༝ There is active transport of the vitamin at the intestinal mucosal brush
border membrane. Both ascorbate and dehydroascorbate are absorbed
across the buccal mucosa by carrier-mediated passive processes.
༝ Intestinal absorption of dehydroascorbate is carrier-mediated, followed
by reduction to ascorbate before transport across the membrane.
༝ Prior to absorption, ascorbic may be oxidized to dehydroascorbate ,
which may be absorbed by facilitated diffusion.
༝ Although dehydroascorbic acid is absorbed in higher rate than
ascorbate, the amount of dehydroascorbic acid found in plasma and
tissues under normal conditions is low, as cells rapidly reduce
dehyroascorbic acid to ascorbate.
71
Digestion, Absorption & Transport of Vitamin C
༝ Simple diffusion (may occur in stomach and small intestine) provides for
vitamin C absorption with ingestion of higher amounts of the vitamin.
༝ Anion channels in some cells may mediate vitamin C diffusion faster than
the trans porters .
༝ From intestinal cells, ascorbate may diffuses through anion channels
into extracellular fluid and enters plasma by way of capillaries.
༝ Absorbed in the intestine by an energy-requiring, sodium- dependent,
carrier- mediated transport system.
༝ After absorption, ascorbic acid is then transported as a free acid in
plasma into the cells, including leukocytes and red blood cells.
༝ In the tissues, Vitamin C serves as an electron donor for a number of
enzymes.
72
Function & Mechanism of Action
༝ Vitamin C has very complex functional roles in the body as
a cofactor in around eight reactions :
• Collagen s ynthes is
• Carnitine synthesis
• Tyrosine synthesis and catabolism
• Neurotransmitter synthesis.
• Drug and steroid metabolism.
• Maintain the iron and copper atoms in the metalloenzymes in the
• reduced s tate.
In addition vitamin C acting role as reducing agent in enzymatic
• reactions.
Ascorbate may also act as an antioxidant against oxidative
stress or oxidation by free radicals
73
Role of Vitamin C
༝ Vitamin C acts as an electron donor for 8 different
enzymes:
Three enzymes participate in collagen hydroxylation.
Two enzymes are necessary for synthesis of carnitine.
Three remaining enzymes have the following functions in
• Dopamine β-hydroxylase participates in biosynthesis of
co mmon, but have other functions as well:
74
Vitamin C and Colds
༝ Vitamin C is thought to moderate colds by enhancing many
immune cell (such as some leukocyte) functions while also
destroying histamine, which causes many of a cold’s
symptoms.
75
Interaction with Other Nutrients
༝ Vitamin C & Iron ༝ Vitamin C & Copper
༝ Increase intestinal absorption ༝ May increase absorption and
of non-heme iron excretion of heavy metals
༝ Reduce Fe3+ to Fe2- for ms a ༝ Vitamin C intakes above 600
soluble complex with iron in mg/d may interfere with
alkaline pH of SI. copper metabolism.
༝ Effects on iron distribution in
the body. ༝ Vitamin C & Folate
༝ Vit.C aids incor poration of iron
༝ Vitamin C helps keep folate in
into ferritin
its reduced and active form.
༝ Excessive iron in presence of
Vit. C can accelerate oxidative
catabolis m of Vit. C. 76
Excretion of Vitamin C
༝ Excretion through urinary excretion
༝ Excretion of vitamin C reduced when intake of vitamin C is
low
༝ Body pool <1.500mg leads to only metabolites in urine
༝ Body pool > 1500mg leads to proportionately more
ascorbate in urine
༝ Vitamin C may be excreted intact or oxidized by L-ascorbate
oxidase to oxalic acid, primarily in liver and some in kidney.
77
RDA of Vitamin C
Adult male : 90mg
Adult female : 75 mg
Pregnancy : 100my
Lactating : 120mg
Smokers : extra 35 mg
UL : adult 2000mg.
Symptoms of Vitamin C Deficiency
༝ Scurvy , impaired connective tissue synthesis and fragility of
blood vessels causes abnormal bleeding: easy bruising,
subcutaneous hemorrhagic spots, inflamed and bleeding
gums, joint stiffness and pain (due to bleeding into joints)
༝ Impaired wound healing
༝ Build-up of keratin in hair follicles producing rough
“sandpaper s kin”
༝ Weaknes s , exhaus tion, fatigue (due to impaired carnitine
synthesis).
༝ Impaired immunity with increased risk of infection.
༝ Diminished antioxidant defenses: increase risk of cancer,
heart disease, stroke, cataract.
79
People at High Risk of Vitamin C Deficiency
༝ Increased physical stress (e.g. infection, fever, burns,
surgery, trauma to soft tissues or bones, and chronic
illnesses such as hyperthyroidism, diabetes, rheumatoid
arthritis, alcoholism, and kidney failure).
༝ Chronic use of drugs such as aspirin and oral
contraceptives impair vitamin C status.
༝ Older people, particularly those with chronic illness, and
aging.
༝ Periods of rapid growth –childhood, adolescence,
pregnancy, and lactation.
༝ Regular cigarette smoking sharply increases breakdown
and excretion of vitamin C.
80
Toxicity of Vitamin C
༝ Toxicity is rare, because vitamin C is generally regarded as safe
in usual doses (up to 1000 mg)
༝ Tolerable upper intake level of 2g vitamin C/day
༝ The most common side effect with ingestion of large amounts (2
g) of the vitamin is gastrointestinal problems characterized by
abdominal pain and osmotic diarrhea.
༝ Other side effects include increased risk of kidney stones for
those with renal disease and iron toxicity for those with iron
metabolism disorders
༝ Large doses may precipitate hemolysis in patients with glucose
6-phosphate dehydrogenase deficiency.
༝ Vitamin C is metabolized to oxalic acid. Increased consumption
increases the urinary concentration of oxalic acid and increases
the risk of oxalate stone formation 81
Uses of Vitamin C in Prevention and Therapy
༝ Enhance ability to fight infection, Vitamin C s timulates the
activity and ability of WBCs to destroy bacteria and viruses.
༝ Treatment of cold and flu: At doses of 1-2 g, it slightly
increases body temperature → ↑functions of WBCs and
↓blood histamine → ↑immune response and ↓nasal &
bronchial congestion → ↓duration and symptoms of cold
and flu.
༝ Helps reduce risk of cancer: particularly cancers of GIT,
bladder, breast, pancreas, and uterus (antioxidant +
enhancer for immune defenses against cancer and + helps
detoxify carcinogenic food additives e.g. nitrates, pesticides,
and other chemicals and heavy metals).
82
༝ Large doses ↓ platelet aggregation → reduce risk of blood
clots. In addition, vitamin C ↑ the strength of blood vessel
walls. By these mechanisms, vitamin C can protect from
coronary heart disease, thrombotic stroke, and peripheral
vascular disease.
༝ Protection from heavy metals: It will ↓absorption and
detoxification and ↑excretion of heavy metals .
↑
༝ Improves healing of wounds and fractures in burns,
trauma, and surgery.
༝ Iron deficiency (by iron absorption from meals).
༝ Preventing and curing Scurvy.
83
Recommended Therapeutic Doses
༝ For scurvy, 100-250 mg once or twice daily.
༝ For treating the common cold, 1-3 g daily.
༝ During acute stress, 1 g (3 times daily)
༝ For preventing sunburn, 2 g of vitamin C and 1000 IU
vitamin E has been used.
84
Vitamin C and Drug Interaction
༝ Vitamin C → ↑chromium and aluminium absorption. Patients with
renal failure who take (Al) compounds should avoid vitamin C in
doses above the RDA.
༝ Vitamin C can destroy dietary vitamin B 12 (taken at least 2 hours
after meals ).
༝ Acidification of the urine by vitamin C could increase reabsorption
of salicylates by the renal tubules, and increase plasma salicylate
levels
༝ High doses of vitamin C can ↓ the response to warfarin, possibly
by causing diarrhea and reducing warfarin absorption
༝ Aspirin increases elimination of vit C. It reduces tissue & leukocyte
its uptake, leaving more in the plasma to be excreted into the urine.
༝ E strogens can ↓vitamin C abs orption or ↓its breakdown.
85
Hubungan stress dengan vitamin c? apakah pd manusia sama?
Vit c kebutuhan meningkat pd kondisi tertentu salah satunya kondisi
stress
Tdk hanya stress mental, tetapi juga Stres fisik = kondisi infeksi, mau
operasi, luka bakar, trauma > scr biologis tubuh perlu peningkatan
kebutuhan vitamin c krn vit c dperlukan untuk beberapa kondisi spt pd
infeksi membantu meningkatkan respon imun untuk memerangi infeksi
Pd manusia, kondisi tsb bisa tjd
Kondisi stress tubuh perlu asupan vit c lbh tinggi sayang pd manusia tdk
bisa mensintesis vit c scr mandiri
Vit c disintesisn melalu jalur asam uronat namun pd manusia tdk bisa
mensintesis krn tidak ada 1 enzim yg paling berperan pd proses akhir
sintesis vitamin c > pd manusia kondisi stress harus menambah asupan
vit c
Pd hewan bisa mensintesis sendiri krn enzim tsb masih ada > tdk perlu
peningkatan asupan/suplementasi vit c
Manusia kondisi stress utamanya stress fisik > perlu peningkatan asupan
vit c
Vit c dapat diekskresikan dlm bentuk batu ginjal/batu oksalat > pencetus batu
ginjal
Dpt mencukupi melalui makanan > dr makanan apakah bisa alami overdosis
dan alami efek negative /tidak?
Dr makanan tergantung kapasitas individu (dosis maksimal 2 gr/hari krn
simpanan tubuh 1,5 gr) > untuk dpt vit c dgn kadar 2 gr dr makanan perlu
makan seberapa (eg buah jambu 100 gr mengandung 10 mg vit c = untuk capai
dosis toksis missal 2.000 perlu mengkalikan 200 > mungkin 2 kg jambu
dimakan sehari)
Toksisitas dr makanan jarang tjd > umumnya tjd krn suplementasi (tablet,
minuman) > dlm ukuran kecil / sekali minum bisa capai dosis berkali-kali lipat
dan tidak tergantung kapasitas perut
88
This was it!
Thank you and have a great rest of the day and remaining week!
Stay healthy, and keeping your distance to stay safe.
Further question ?
[email protected]
@dianmuninggar
+6285727100005
89
Diterjemahkan dari bahasa Inggris ke bahasa Indonesia - www.onlinedoctranslator.com
2
Vitamin B1 (Tiamin)
5
Sumber
6
Metabolisme
7
Kekurangan
༝ kelemahan ༝ busung
༝ degenerasi saraf ༝ pembesaran jantung
༝ sifat lekas marah ༝ gagal jantung
༝ kekurangan tangan/kaki
koordinasi
༝ kerusakan
transmisi ke
sistem saraf
8
Risiko Kekurangan
9
Penilaian Tiamin
༝ Ekskresi tiamin dalam urin
༝ Konsentrasi tiamin dalam darah / serun
༝ Aktivitas transketolase eritrosit
༝ Aktivasi apo-transketolase yang terkandung dalam eritrosit
produk lisis dengan penambahan tiamin difosfat in vitro telah
digunakan sebagai indeks status tiamin.
10
Riboflavin (Vitamin B2)
cincin isoalocsazine dengan rantai samping pita
Gambaran
12
13
Komponen rantai respirasi di mitokondria
* koenzim untuk oksidasi - reaksi reduksi dalam proses respirasi seluler 14
Metabolisme
15
Sumber
༝ susu
༝ Jantung
༝ Daging
༝ telur
༝ Sayuran hijau
16
Kekurangan
Ariboflavinosis:
༝ Glositis, cheilosis, dermatitis seboroik, stomatitis, mata &
gangguan tenggorokan, gangguan sistem saraf
17
Risiko Kekurangan
༝ Jarang terjadi
༝ Kurangnya asupan susu dan produknya
༝ alkoholik
༝ Penggunaan fenobarbital jangka panjang A penghambat flavokinase
18
Niasin : Asam nikotinat
(Vitamin B3)
Mengandung bentuk asam dan amida
Gambaran
21
Metabolisme
22
Sumber
༝ Jamur
༝ biji-bijian
༝ Daging, ikan
༝ Jagung A niasin dan triptofan yang buruk
23
Kekurangan
Pelagra
༝ ditandai dengan gejala depresi, fotosensitif,
dermatitis dan diare
24
Penilaian Niasin
25
Asam Pantotenat
Dikenal sebagai vitamin B3, yang terdiri dari -alanin &
asam pantoat
Fungsi
༝ Bagian dari Koenzim-A A bertindak sebagai pembawa gugus asil
༝ Penting untuk metabolisme karbohidrat, lemak & protein
༝ metabolisme asam lemak
༝ metabolisme karbohidrat (siklus asam sitrat dan glukoneogenesis)
༝ sintesis asetilkolin, hormon steroid, kolesterol, dan
fosfolipid
༝ sintesis porfirin, yang diperlukan untuk pembentukan
hemoglobin
Metabolisme
28
Sumber
༝ Sayuran segar
༝ Biji & Kacang
༝ Susu, Telur, Daging
29
Kekurangan
30
Vitamin B6
Metabolisme
32
Fungsi
༝ Koenzim: PLP, PMP
༝ transaminasi, dekarboksilasi, deaminasi,
dan reaksi rasemisasi diperlukan
༝ Koenzim untuk fosforilasi glikogen
33
Fungsi
༝ PLP membantu proses yang menghasilkan
neurotransmiter: epinefrin, norepinefrin, dopamin,
serotonin, dan GABA
༝ PLP membentuk prekursor hem dalam hemoglobin.
༝ PLP diperlukan untuk mengubah triptofan menjadi niasin.
༝ PLP terlibat dalam transformasi linoleat
asam menjadi asam arakidonat
༝ PLP penting dalam pembentukan sel saraf
lapisan mielin.
༝ Piridoksin memainkan peran penting dalam pertumbuhan sel
dan divisi.
34
Sumber
༝ Biji
༝ biji-bijian
༝ Hati
༝ telur
༝ susu
༝ Sayuran hijau segar
35
Kekurangan
༝ Tua
༝ Terapi TBC (isoniazid pyridoxal-hidrazon)
༝ pecandu alkohol A alkohol mengurangi penyerapan, menghancurkan
bentuk koenzim 36
Vitamin B12 (Cobalamin)
Gambaran
38
Sumber
༝ Daging
༝ susu
༝ Ikan
༝ Produk sintesis dari mikrobakteri usus
༝ Tidak tersedia di tumbuhan
39
Metabolisme & Penyerapan
40
Fungsi
sebagai Koenksim 3'-deoksi-adenosil-kobalamin
41
Fungsi
༝ Vit B12 diperlukan untuk mengaktifkan asam folat
༝ Vit B12 diperlukan untuk fungsi normal semua sel, dalam
saluran pencernaan, sumsum tulang dan jaringan saraf.
༝ kofaktor dari 2 jenis enzim; metionin sintetase
metilalonil koA mutase.
42
Kekurangan
anemia megaloblastik
༝ Perangkap metil-folat
༝ Tertunda atau kegagalan pembelahan sel normal karena gangguan
sintesis DNA
sakit saraf
༝ mielinisasi yang rusak
༝ pelemahan perifer progresif
43
Risiko Kekurangan
༝ Vegetarian
༝ Bayi yang disusui oleh vegetarian
༝ Tua
44
Gambaran
༝ Folacin adalah istilah umum untuk asam folat & semua senyawa
yang memiliki aktivitas seperti asam folat
༝ Asam folat mengandung pteridin yang mengikat p-
asam aminobenzoat (PABA) & glutamat
༝ Hewan tidak dapat mensintesis PABA atau mengikat glutamat dalam
asam pteriuk, sehingga membutuhkan folat dari makanan
46
Fungsi
Koenzim: tetrahidrofolat (THF)
༝ THF penting dalam reaksi transfer/pembawa 1
atom karbon berupa metil, metilena, formimino, formil,
metenil
༝ Penting dalam sintesis serin, metionin, glisin,
purin, pirimidin
༝ Diperlukan pada wanita hamil A peningkatan sel darah
proliferasi; khususnya pada trimester pertama
47
Asam tetrahidrofolat dan folat tersubstitusi satu karbon
48
49
Sumber
༝ Ragi
༝ Hati
༝ Daging
༝ Sayuran Segar (terutama asparagus)
༝ Buah-buahan
༝ Biji-bijian utuh
༝ Gila
50
Metabolisme
༝ Sel usus
༝ folat direduksi menjadi tetrahidrofolat oleh folat reduktase,
dihambat oleh methotrexate (obat kemoterapi)
༝ dimetilasi menjadi N5-metil-THF; bentuk darah primer
51
Kekurangan
༝ Anemia megaloblastik
༝ Cacat tabung saraf
52
Anemia megaloblastik
53
Cacat Tabung Saraf
HN NH
HC CH
H2C CH-(CH2)4COOH
S
Sumber
༝ Sebagian besar produk flora usus
༝ Jagung
༝ Kedelai
༝ Daging
༝ Ikan
༝ Kuning telur
༝ Tomat
58
Kekurangan
༝ Jarang terjadi
༝ Kecuali bila ada gangguan penyerapan atau pemanfaatan
antibiotik untuk jangka panjang
59
Vitamin C
Bentuk fisiologis aktif untuk vitamin C
Gambaran
༝ Dia vitamin yang larut dalam air, biasanya terdapat pada buah-buahan dan
sayur-sayuran.
1
15
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an ng ind
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ba m li
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Masalah terkait vitamin C disebut sebagai curangdan
ap ka ng
ip n k
terkait dengan kekurangan vitamin C telah cukup lazim
en jer ata
ya uk n
ki
tk
ud
is
62
“
Penyakit kudis adalah umum di antara
63
Kimia & Stabilitas Vitamin C
65
༝ Vitamin C memiliki sejumlah vitamer yang memiliki aktivitas vitamin
C pada hewan:
༝ Asam askorbat dalam sistem biologis (pH rendah)
༝ Bentuk teroksidasi asam deihroaskorbat.Askorbat
༝ dalam larutan garam netral (pH>5)
༝ Askorbat dan asam askorbat keduanya secara alami ada di dalam tubuh,
karena bentuk-bentuknya saling berkonversi sesuai dengan pH.
66
Sensitivitas Vitamin C
67
Sumber Vitamin C Alami
Jambu biji jeruk lemon
.
68
Sumber Vitamin C Alami
Prem paprika merah Pepaya
.
Kiwi Brokoli
.
69
Sumber Vitamin C
70
Pencernaan, Penyerapan & Transportasi Vitamin C
༝ Setelah penyerapan, asam askorbat kemudian diangkut sebagai asam bebas dalam
plasma ke dalam sel, termasuk leukosit dan sel darah merah.
༝ Dalam jaringan, Vitamin C berfungsi sebagai donor elektron untuk sejumlah
enzim.
72
Fungsi & Mekanisme Aksi
73
Peran Vitamin C
74
Vitamin C dan Pilek
75
Interaksi dengan Nutrisi Lain
77
RDA Vitamin C
Pria dewasa : 90mg
Wanita dewasa : 75 mg
Kehamilan : 100my
Menyusui : 120mg
perokok : ekstra 35 mg
UL : dewasa 2000 mg.
Gejala Kekurangan Vitamin C
82
༝ Dosis besar ↓ agregasi trombosit → mengurangi risiko pembekuan
darah. Tambahan,vitamin C ↑ kekuatan pembuluh darahdinding.
Dengan mekanisme ini, vitamin C dapat melindungi daripenyakit
jantung koroner, stroke trombotik, dan penyakit pembuluh
darah perifer.
༝ Perlindungan dari logam berat: Itu akan ↓ penyerapan
dan↑detoksifikasi dan ↑ ekskresi logam berat.
༝ Meningkatkan penyembuhan luka dan patah tulang pada luka bakar,
trauma, dan pembedahan.
༝
༝
Kekurangan zat besi (oleh penyerapan zat besi dari makanan).
83
Dosis Terapi yang Direkomendasikan
84
Vitamin C dan Interaksi Obat
[email protected]
@dianmuninggar
+ 6285727100005
87
Metabolisme Lemak
Setyo Prihatin
Metabolisme LIPID
Degradasi Lipid Oksidasi asam lemak
Pencernaan, penyerapan dan transpot lemak
-oksidasi asam lemak
Biosintesis Lipid
Biosintesis asam lemak
Biosintesis triasilgliserol
Biosintesis fosfolipid
Biosintesis kolesterol dan steroid
Pengertian
ikatan2 organik terdiri atas C, H dan Oyang mempunyai
sifat dapat larut dalam pelarut non polar (petroleum,
eter, kloroform, benzene)
Tata Nama
Didasarkan atas nama asam lemak penyusunnya. Penamaan
bergantung pada jumlah C- nya diberi akhiran oat (oic)
untuk lemak jenuh dan enoat (enoic) untuk tidak jenuh
Terdapat nama umum yang telah dikenal seperti asam
palmitat, stearat,
Merupakan istilah yang meliputi senyawa-
senyawa heterogen :
- lemak dan minyak (umum dikenal dlm makanan)
- malam, fosfolipida, sterol
Klasifikasi (kimia)
. Lipida sederhana
Lemak netral
monogliserida, digliserida dan trigliserida (ester asam
lemak dengan gliserol)
Ester asam lemak dengan alcohol
malam, ester sterol, ester non sterol, ester vitamin A dan
D
Lipida majemuk
Fosfolipida
Lipoprotein
Glikolipida
. Lipida turunan (derived lipids)
Asam lemak
Sterol
kolesterol dan ergosterol
hormon steroida
Vitamin
Garam Empedu
Klasifikasi (fungsi biologik)
Lemak simpanan : trigliserida
Lemak structural : fosfolipida dan kolesterol
ASAM LEMAK :
Panjang Rantai
As.lemak rantai pendek (≤ 6 C) susu
mengandung 10% as.lemak rantai pendek asam
butirat (C4))
As.lemak rantai sedang (8 – 12 C) minyak
kelapa dan minyak kelapa sawit (Laurat (C12)
As.lemak rantai panjang (14 – 18 C) lemak
hewani dan minyak nabati Palmitat (C16)
As.lemak rantai sangat panjang (≥ 20 C)
minyak ikan (Arakidonat) (C20)
Trigliserida
ester gliserol antara 1 molekul gliserol + 3
molekul asam lemak
Bila 1 as.lemak bergabung dgn gliserol
monogliserida
Bila 2 as.lemak bergabung dgn gliserol
digliserida
Di alam sebgn besar lemak & minyak tdd 98-
99% trigliserida
Lipoprotein
Gabungan molekul lipida & protein yg
disintesa di hati
Bgn dlm lipoprotein tdd : trigliserida &
kolesterol yg diselubungi fosfolipida
Fungsi : transport lipida di dlm plasma ke
jaringan2 yg membutuhkan sbg :
a) sbr energi;
b) komponen membran sel;
c) prekursor metaboli aktif
Lipoprotein Density Diameter Protein % Phosphol Triacylglycerol
class (g/mL) (nm) of dry wt ipid % % of dry wt
HDL 1.063-1.21 5 – 15 33 29 8
LDL 1.019 – 18 – 28 25 21 4
1.063
IDL 1.006-1.019 25 - 50 18 22 31
VLDL 0.95 – 30 - 80 10 18 50
1.006
most proteins have densities of about 1.3 – 1.4 g/mL and lipid aggregates usually
have densities of about 0.8 g/mL
Pencernaan, penyerapan, &
transport lemak
Penggunaan lemak sebagai sumber
energi erat berhubungan dengan
metabolisme lipoprotein dan
kolesterol.
Mammal mempunyai 5 – 25% / lebih
lipid dan 90% dlm bentuk lemak
(TAG) yg disimpan di dalam jaringan
adipose
Sumber lemak :
Makanan
Biosintesis de novo
Kalsium.
Fosfor.
Natrium.
Kalium.
Klorida.
Magnesium.
KALSIUM.
Dewasa; osteomalasia
FOSFOR
- Kromium - Selenium
- Kobalt - Silikon
- Tembaga - Seng
- Yodium - Flourida
- Besi
- Mangan
- Molibdenum
KROMIUM
Fungsi: Kromium trivalen, konstituen ‘faktor
toleransi glukosa” yang berikatan ke dan
meningkatkan potensi insulin.
Penyakit: Gangguan toleransi glukosa;
sekunder akibat sutrisi parenteral
Sumber: Daging, hati, ragi (brewer’s yeast),
padi-padian, whole grain, kacang-kacangan,
keju.
KOBALT
Lintasan
Katabolisme
Metabolisme
Lintasan
Anabolisme
Lintasan
Amfibolik
• Hubungan katabolisme dan Anabolisme
Metabolisme :
• Karbohidrat
• Lipid
• Protein
• Pengendalian Metabolisme
Hubungan katabolisme
dan anabolisme
Hubungan metabolisme karbohidrat,
Lipid, Protein dan Asam Nukleat
ATP merupakan fosfat berenergi tinggi yg digunakan
dalam tubuh untuk metabolisme
Glc darah
Kenyang meningkat Insulin
Metabolisme
karbohidrat
Glukagon
Puasa Glc darah Epineprin
menurun
ACTH
Glukokortikoid
GH
Tiroid
Hipotalamus
Insulin Fosforilasi
Glikogenesis
HMP Shunt
Asam uronat
Gula Amino
Galaktosa
Aerob = 8 ATP
Glikolisis
Siklus Krebs
30 ATP
Rantai
respirasi
Catatan :
1 mol NADH = 3 mol ATP
1 mol FADH2 = 2 mol ATP
1 mol Asetil koA = 12 mol ATP
Sumber fosfat berenergi tinggi Senyawa non fosfat berenergi
tinggi
1. Glikolisis
1. Asetil koA
- 1,3 bifosfogliserat
2. S-adenosil metionin
- Fosfoenolpiruvat (PEP)
3. Asil Carier protein
2. Siklus Krebs
4. Fosforibosilpirofosfat
Suksinil koA
(PRPP)
3. Rantai respirasi
5. UDP-glukosa
4. Kreatin fosfat
Senyawa fosfat berenergi rendah
5. Karbamoil Fosfat 1. Glukosa 6P
2. Fruktosa 6P
3. Gliserol 3P
4. AMP
Jumlah energi bebas
Siklus ATP/ADP
Karbohidrat dalam Makanan
Usus halus
monosakarida
1. glukosa (terbanyak)
2. fruktosa
3. galaktosa
absorbsi
Darah
metabolisme karbohidrat
Metabolisme karbohidrat
Fungsi Glukosa
1. Sumber Energi utama bagi sel
2. Bahan Pembentuk zat lain yang diperlukan
tubuh
ex : - pentosa (RNA, DNA)
- asam glukoronat
- Glikoprotein
- Glikosaminoglikan
- Laktosa (ibu menyusui)
Glikolisis Embden Meyerhof
• KoASH CO2
Piruvat Dehidrogenase
Piruvat Asetil KoA
NAD NADH + H+
Siklus Krebs
Pengaruh Insulin Thd Glikolisis
Pembentukan ikatan berenergi tinggi dalam
katabolisme glukoasa
Siklus Krebs (Siklus Asam Sitrat =SAS)
transketolase
Sintesis
Gliseraldehid 3P Sedoheptulosa 5P nukleotida
RNA, DNA
transaldolase
Fruktosa 6P Eritrosa 4P
Transketolase
Fruktosa 6P Gliseraldehid 3P
HMP-Shunt pada eritrosit menyediakan
NADPH untuk mereduksi glutation
teroksidasi menjadi glutation
tereduksi yang dikatalisis oleh
glutation reduktase
Glukagon
Epineprin
+ Glikogenolisis
Puasa Kadar Glc
rendah Glukoneogenesis
Lipolisis
GLIKOGENESIS DAN
GLIKOGENOLISIS
• Laktat (otot)
• Gliserol
• Propionat (lemak)
• Asam amino glukogenik
(aspartat, tirosin, lisin,
glutamat, hidroksi prolin, serin,
alanin, sistein. Glisin)
SIKLUS ASAM LAKTAT (CORI)
Jalur asam uronat
UDP
Glukoronat
aktif
Fungsi UDP-glukoronat
1. Pembentukan proteoglikan
2. Untukkonjugasi steroid, obat tertentu dan
bilirubin (proses xenobiotik)
3. Dengan NADPH glukoronat menjadi L-gulonat
yaitu jalur penghasil asam askorbat (pd
binatang)
4. L-gulonat L-xilulosa Jalur pentosa fosfat
JALUR ASAM URONAT (URONIC ACID PATHWAY)
Metabolisme Galaktosa
Glikosaminoglikan dan
glikoprotein
GLUKOSA DARAH
• Sumber
• KH (makanan)
• Glikogen hati (glikogenolisis)
• Glukoneogenesis
- laktat
- propionat
- gliserol
- asam amino glukogenik
Homoestatis Kadar Glukosa Darah
Hormon Insulin
- Dihasilkan dari sel beta pankreas sebagai
respon hiperglikemia
- Dihambat olen epineprin dan norepineprin
- Meningkatkan transpor glukosa untuk masuk sel
- Meningkatkan penggunaan glukosa, untuk bentuk
ATP, glikogen, lipid
- Meningkatkan absorpsi asam amino protein
Hormon Glukagon
- Dihasilkan di sel alpa pankreas sebagai respon
hipoglikemia
- Berlawanan kerjanya dengan hormon insulin
- Mengaktifkan glikogenolisis di hati dan otot
- Mengaktifkan lipolisis di jaringan adiposa
- Mengaktifkan sintesis dan pelepasan glukosa dari hati
B. Air adalah pelarut universal yang dapat melarutkan garam seperti natrium klorida
(NaCl). Cl bermuatan negative berikatan dengan muatan positif pada ion hydrogen,
dan muatan positif Na+ berikatan dengan muatan negative oksigen. Dengan
demikian, air perlahan melarutkan garam.
Fungsi Air Tubuh
Pertukaran Kapiler.
• Filtrasi terjadi di dekat ujung arteri kapiler karena tekanan hidrostatik kapiler (CHP) lebih besar daripada
tekanan osmotik koloid darah (BCOP).
• Tidak ada pergerakan bersih cairan dekat titik tengah kapiler karena CHP= BCOP.
• Reabsorpsi terjadi di dekat ujung vena kapiler karena BCOPlebih besar daripada CHP.
Tekanan Hidrostatik & Tekanan
Osmotik
• Tekanan hidrostatik sangat penting dalam mengatur pergerakan air pada
nefron ginjal untuk memastikan penyaringan yang tepat dari darah guna
membentuk urin.
• Pergerakan cairan terjadi di antara kompartemen sepanjang gradien
osmotik.
• Di dalam tubuh, air bergerak melalui osmosis dari plasma ke IF (dan
sebaliknya) sertadari IF ke ICF(dan sebaliknya).
• Air akan bergerak secara konstan ke dalam dan ke luar dari kompartemen
cairan ketika ada perubahan kondisi tubuh
• Contoh : saat berkeringat → kehilangan air melalui kulit
• Berkeringat akan mengurangi cairan pd jaringan, ↑ konsentrasi zat terlarut dalam
jaringan tsb.
• Air akan berdifusi dari darahmenjadi kelenjar keringat dan jaringan kulit di
sekitarnya yang mengalami dehidrasi karena adanya gradien osmotik.
• Ketika air meninggalkan darah → digantikan oleh air di jaringan lain di seluruh
tubuh yang tidak mengalami dehidrasi.
• Jika hal ini terus berlanjut, dehidrasi menyebar ke seluruh tubuh.
• Ketika orang yang mengalami dehidrasi minum air dan rehidrasi, air tersebut
didistribusikan kembali oleh gradien yang sama, tetapi dalam arah yang
berlawanan, dan akan mengisi kembali air di semua jaringan.
Perpindahan Zat Terlarut Antar Kompartemen
• Di colon
Absorpsi Na+ dan Cl- diikuti dengan HCO -3
HCO3-dipakai untuk menetralisir asam organik yg dipakai oleh bakteri usus
Bagaimana Cairan & Natrium dapan
Mempengaruhi Tekanan Darah?
• Tubuh menyimpan terlalu banyak cairan→ volume darah meningkat dan
tekanan darah akan meningkat
• Ginjal membantu mengatur volume darah dan keseimbangan elektrolit
melalui sinyal hormon yang dikontrol secara ketat
• Tiga hormon dan satu enzim bekerja sama untuk mengatur retensi dan
ekskresi cairan dan elektrolit berdasarkan volume darah
• Hormon
• Hormon antidiuretik (ADH), juga disebut vasopressin
• Angiotensin
• Aldosterone
• Enzim
• Renin
The Aldosterone Feedback Loop
Aldosteron, yg dilepaskan oleh kelenjar adrenal, memfasilitasi reabsorbsi
Na & cairan
The Renin-Angiotensin System
Angiotensin II menstimulasi pelepasan aldosteron dari korteks adrenal
Volume Darah Mengatur Tekanan Darah
Asupan & Sumber Cairan
• Kebutuhan air dipengaruhi oleh
• Aktivitas fisik
• Faktor lingkungan
• Diet
• Rekomendasi asupan cairan
• 80% dari minuman dan 20% dari makanan
• Wanita dewasa: + 9 gelas cairan/hari
• Pria dewasa: + 13 gelas cairan/hari
Rekomendasi Harian
Gangguan Keseimbangan Air di Dalam Tubuh
• Jumlah/Volume
• Kelebihan Air → Overhidrasi
• Kekurangan Air → Dehidrasi
DEHIDRASI
DEHIDRASI BERAT
Denaturasi protein
Kerusakan sel
Mati
Dehidrasi (Kekurangan Air + Elektrolit)
1. Kehilangan/Pembatasan Air
Dehidrasi Intrasel
Gejala
• sangat haus, mual, muntah
• badan terasa panas dan kering
• urin > pekat dan volume berkurang
Dehidrasi (Kekurangan Air + Elektrolit)
2. Kekurangan Elektrolit
Pemberian air >> tanpa ada / sedikit elektrolit
hipotonis ekstrasel
oedem intrasel
• Diare berat
• Usaha tubuh : (-) / gagal
• Pengobatan :
• mengganti cairan & elektrolit yghilang
• makanan yg sesuai : oral, infus
Edema
• Edema : akumulasi kelebihan air di jaringan,
paling sering terjadi pada jaringan lunak
ekstremitas
• penyebab fisiologis : kebocoran air dari kapiler
darah.
• penggunaan obat-obat terapeutik tertentu
• vasodilator, calcium channel blocker , obatanti-
inflamasi non-steroid, terapi estrogen, obat
diabetes.
• kehamilan
• cedera lokal
• reaksi alergi
• Identifikasi edema subkutan : menekan jari
ke area yang dicurigai.
• Edema (+) bila depresi berlanjut selama bbrp
detik setelah jari diangkat (pitting).
Pemantauan Asupan Cairan
• Pengukuran BBsebelum dan sesudah melakukan aktivitas fisik yang
berat & lama, saat persalinan
• BBlangsung berkurang → kehilangan air tubuh
• BBtiba-tiba bertambah → overhidrasi
• Konsumsi lebih sedikit cairan sebelum melakukan aktivitas berikutnya
Further question ?
[email protected]
+6285727100005