VITAMINS and MINERALS

PREPARED BY: MARIE SY-FAMA,MD, MHCA

VMU COLLEGE OF MEDICINE
DEPT. OF BIOCHEMISTRY
• The Vitamins Are A Disparate Group Of
Compounds With A Variety Of Metabolic
Functions
 • A vitamin is an organic compound that is
required in the diet in small amounts for the
maintenance of normal metabolic integrity

• Needed for a variety of biochemical functions

• Generally, cannot be Deficiency causes a
synthesized by the body specific disease, which
and must therefore be is cured or prevented
supplied in the diet only by restoring the
vitamin to the diet
Exemption:
– Vitamin D formed in the In excess of body’s
skin metabolic capacity can
– Niacin formed from lead to toxicity
Tryptophan
• Level of intake:
adequate only for
normal health and
the maintenance of • Individuals do not all
metabolic integrity have the same
requirement

• If it is observed that
individual requirements
are distributed
statistically in the range
of +/− 2 standard
deviation (SD) around
the mean
 Characteristics
• Occur in natural foods as such or as utilizable
precursors
• Obtained thru the diet: not synthesize in the body
or synthesized in inadequate amount
• Converted to substances that participates in
reactions essential for the proper functioning of
cells
• Do not enter into tissue structure
• Not degraded to provide energy
• Unlike hormones they are of exogenous source
 What vitamins are not
• Not “pep pills” and have no
caloric or energy value of
their own
• Vitamins cannot
• Not substitute for the major replace food
nutrients, minerals or water

• Not component of body

structures • Vitamins cannot be
assimilated without
• Cannot take vitamins, stop
eating and be healthy ingesting food
 Two major groups

• Water-soluble vitamins
- B complex and Vitamin C

• Fat-soluble vitamins
- A, D E, K
 Water soluble Fat soluble
Absorption absorbed with water needs fat for
absorption
Transport easily transported in transported by
the blood plasma lipoproteins/albumin
Storage no storage except Vit stored in the liver and
B12 stored in the liver adipose tissue

Excretion kidneys thru the urine bile thru the feces

Toxicity unusual: not stored in easy to develop

the body toxicity
Deficiency easy to develop rare
LIPID-SOLUBLE VITAMINS

VITAMIN A
• Types of Vit A
1. Vit A1 or Retinol
Vit A2 or Dehydroretinol has 40 %
potency of retinol
2. Vit A aldehyde or Retinaldehyde
3. Vit A acid or Retinoic acid
Sources
• Carotenoids
• Plant precursors
• Provitamin A • Retinoids
• Cleaved to yield • Preformed vitamin A
different types of Vit A • Animal origin
• retinol
• retinaldehyde
• retinoic acid
• The α-, β-, and γ- • B-carotene has the
carotenes and highest activity
cryptoxanthin • About 6 μg of β-
quantitatively the carotene is equivalent
most important to 1 μg of preformed
provitamin A retinol expressed as
carotenoids ug of retinol activity
equivalents (RAE)
 • Food sources
- liver, egg yolk,
butter , milk are the
good sources of
preformed retinol
• Dark green and yellow
vegetables, carrots,
sweet potatoes and
fruits are good
sources of
carotenoids
ABSORPTION

Beta-carotene and other carotenoids are

Carotene Dioxygenase
retinaldehyde
reduced
retinol
esterified/secreted
chylomicrons

• for preformed Vit A 80-90 percent absorbed

• for beta carotene only 40-60 percent
 Vitamin A Has a Function in Vision

• In the retina, retinaldehyde functions as the

prosthetic group of the light-sensitive opsin proteins
forming rhodopsin (in rods) and iodopsin (in cones)
 all-trans-retinol
In the pigment epithelium isomerized
of the retina
11-cis-retinol
oxidized

11-cis-retinaldehyde reacts
lysine residue in opsin

rhodopsin
absorption of light isomerized
all-trans retinaldehyde
a conformational change in opsin

This results in the release of retinaldehyde from protein

rhodopsin and the initiation of a nerve impulse
• In Vitamin A deficiency both the time taken to adapt
to darkness and the ability to see in poor light are
impaired
Role in the Regulation of GeneExpression & Tissue
Differentiation

• Most important function: the control of cell

differentiation and turnover

• All-trans-retinoic acid and 9-cis-retinoic acid

regulate growth, development and tissue
differentiation

• They have different actions in different tissues

• Retinoic acid binds to nuclear receptors that bind to
response elements of DNA and regulate the
transcription of specific genes

• There are two families of nuclear retinoid receptors:

1. the retinoic acid receptors (RARs)
- bind all trans –retinoic acid or 9-cis-retinoic acid

2. the retinoid X receptors (RXRs)

-bind 9-cis-retinoic acid
Vitamin A deficiency is a major public health problem
worldwide

• Vitamin A deficiency is • More prolonged

the most important deficiency leads to
preventable cause of
blindness xerophthalmia:
• The earliest sign of keratinization of the
deficiency is a loss of cornea and skin and
sensitivity to green light,
followed by impairment blindness
of adaptation to dim
light, followed by night
blindness
 • Vitamin A also has an important role in
differentiation of immune system cells, and mild
deficiency leads to increased susceptibility to
infectious diseases
(anti-infective vitamin)
• There is only a limited capacity to metabolize
vitamin A and excessive intakes lead to
accumulation beyond the capacity of binding
proteins, so that unbound vitamin A causes
tissue damage
 Vitamin A Is Toxic in Excess
• Symptoms of toxicity affect the central nervous
system - headache, nausea, ataxia, and anorexia,
all associated with increased cerebrospinal fluid
pressure
• Affects the liver causing hepatomegaly with
histologic changes and hyperlipidemia
• Affects calcium homeostasis causing thickening
of the long bones, hypercalcemia and calcification
of soft tissues
• Affects the skin causing excessive dryness,
desquamation, and alopecia
VITAMIN D: A HORMONE
Vitamin D is not strictly a vitamin
since it can be synthesized
in the skin, and under most
conditions that is
its major source

• Only when sunlight is inadequate is a

dietary source required.
 The main function of vitamin D is in
the regulation of calcium absorption
and homeostasis

• Most of its actions are mediated by way of

nuclear receptors that regulate gene
expression
• Deficiency—leading to rickets in children and
osteomalacia in adults—continues to be a
problem in northern latitudes, where sunlight
exposure is poor
 Vitamin D Is Synthesized in the Skin
• 7-Dehydrocholesterol
undergoes a nonenzymic reaction on exposure to
ultraviolet light, yielding

previtamin D
undergoes a further reaction over a period of hours to form
the vitamin itself

cholecalciferol
which is absorbed into the bloodstream
Vitamin D is metabolized to the active metabolite
calcitriol in liver & kidney

• In the liver, cholecalciferol, which has been

synthesized in the skin or derived from food is
hydroxylated to form the 25-hydroxy derivative
calcidiol

• released into the circulation bound to a vitamin

D-binding globulin which is the main storage
form of the vitamin
• In the kidney, calcidiol undergoes either:

- 1-hydroxylation to yield the active metabolite

1,25-dihydroxyvitamin D (calcitriol)
or
- 24-hydroxylation to yield an inactive metabolite
24,25-dihydroxyvitamin D (24-hydroxycalcidiol)

• Ergocalciferol from fortified foods undergoes similar

hydroxylations to yield ercalcitriol
Vitamin D regulates its own metabolism and is also regulated
by calcium homeostasis

• Calcitriol acts to reduce its own synthesis by:

- inducing the 24-hydroxylase
- and repressing the 1-hydroxylase in the kidney
• Its principal function is to maintain the plasma
calcium concentration.
• Three ways:
1. it increases intestinal absorption of calcium
2. reduces excretion of calcium (by stimulating
reabsorption in the distal renal tubules)
3. mobilizes bone mineral
In addition, calcitriol is:
• involved in insulin secretion, synthesis and secretion of
parathyroid and thyroid hormones

• inhibition of production of interleukin by activated T

lymphocytes and of immunoglobulin by activated B
lymphocytes

• differentiation of monocyte precursor cells, and

modulation of cell proliferation

In its actions, it behaves like a steroid hormone,

binding to a nuclear receptor protein
Vitamin D deficiency affects children & adults

• In the vitamin D deficiency disease rickets, the

bones of children are undermineralized as a
result of poor absorption of calcium.

• Osteomalacia in adults results from

demineralization of bone in women who have
little exposure to sunlight, often after several
pregnancies.
• Although vitamin D is essential for prevention
and treatment of osteomalacia in the elderly,
there is little evidence that it is beneficial in
treating osteoporosis
 Vitamin D Is Toxic in Excess
• Some infants are sensitive to intakes of
vitamin D as low as 50 μg/d, resulting in an
elevated plasma concentration of calcium

• This can lead to contraction of blood vessels,

high blood pressure, and calcinosis—the
calcification of soft tissues
 • Excessive exposure to sunlight does not lead to
vitamin D poisoning because there is a limited
capacity to form the precursor 7-dehydrocholesterol
and to take up cholecalciferol from the skin.
VITAMIN E
Does not have a precisely defined metabolic
function
No unequivocal unique function for Vitamin E
has been defined

• It does act as a lipid-soluble antioxidant in cell

membranes, where many of its functions can
be provided by synthetic antioxidants
• Vitamin E is the generic descriptor for
two families of
compounds:
1. Tocopherols
2. Tocotrienols
• The different vitamers (compounds having
similar vitamin activity) have different biologic
potencies

• The most active is D-α-tocopherol and it is usual

to express vitamin E intake in milligrams of D-α-
tocopherol equivalents

• Synthetic DL-α-tocopherol does not have the

same biologic potency as the naturally occurring
compound
 Vitamin E is the major lipid-soluble
antioxidant in cell membranes & plasma
lipoproteins
• It reacts with the lipid
peroxide radicals
formed by peroxidation
of polyunsaturated
fatty acids before they • The tocopheroxyl+free
can establish a chain radical product is
reaction (chain breaker) relatively unreactive
and ultimately forms
nonradical compounds
 Role of Vit C
• The tocopheroxy+free radical product is reduced
back to tocopherol by reaction with Vitamin C

• The resultant monodehydroascorbate+free radical

then undergoes enzymic or nonenzymic reaction to
yield ascorbate and dehydroascorbate
• The tocopheroxyl+free radical is a very a
stable compound

• It can an penetrate farther into cells and

potentially, propagate a chain reaction

Therefore, vitamin E may, like

other antioxidants, also have pro-oxidant
actions, especially
at high concentrations
 IN EXPERIMENTAL ANIMALS, VITAMIN E
DEFICIENCY RESULTS IN
RESORPTION OF FETUSES AND TESTICULAR
ATROPHY
Dietary vitamin E deficiency in humans is
unknown

Except:
• patients with severe fat malabsorption, cystic
fibrosis and some forms of chronic liver disease

• suffer deficiency because they are unable to

absorb the vitamin or transport it

• exhibiting nerve and muscle membrane damage

• In premature infants born with inadequate reserves
of the vitamin, their erythrocyte membranes are
abnormally fragile as a result of peroxidation, which
leads to hemolytic anemia
VITAMIN K
REQUIRED FOR SYNTHESIS OF
BLOOD-CLOTTING PROTEINS
• Vitamin K discovery
- a result of investigations into the cause of a
bleeding disorder
- hemorrhagic (sweet clover) disease of
cattle
- hemorrhagic disease of chickens fed on a
fat-free diet
• The missing factor in • The cattle feed with
the diet of the chickens sweet clover contained
was Vitamin K Dicumarol, an
antagonist of vitamin K

Antagonist of vitamin K are used to reduce blood

coagulation in patients at risk of thrombosis—the most
widely used agent is Warfarin
Three compounds have the biologic activity of
Vitamin K
1. Phylloquinone
- the normal dietary source, found in green
vegetables
2. Menaquinones
- synthesized by intestinal bacteria, with differing
lengths of side-chain
3. Menadione, menadiol and menadiol diacetate
- synthetic compounds that can be metabolized to
phylloquinone
• Menaquinones are absorbed to some extent but
its biological activity is not clear

• It is possible to induce signs of vitamin K deficiency

simply by feeding a Phylloquinone deficient diet
without inhibiting intestinal bacterial action
• Vitamin K is the cofactor for the carboxylation
of glutamate residues of calcium binding
protein to form the unusual amino acid γ-
carboxyglutamate (Gla), which chelates the
calcium ion
1. Vitamin K hydroquinone is oxidized to epoxide
by Vit K epoxidase

2. Epoxide activates a glutamate residue in the

protein
substrate to a carbanion

3. Carbanion reacts nonenzymically with carbon

dioxide to form γ-carboxyglutamate
 • In the presence of Warfarin, Vitamin K
epoxide cannot be reduced but accumulates,
and is excreted

• A high dose of Vitamin K is the antidote to an

overdose of warfarin
 Vit K dependent clotting factors

• Prothrombin and Factors VII, IX and X, and

proteins C and S) each contain between
four and six γ-carboxyglutamate residues
which chelate calcium ions and so permit
the binding of the blood clotting proteins
to membranes
 Abnormal precursor of prothrombin
(preprothrombin)

• In Vitamin K deficiency or in the presence

of Warfarin, an abnormal precursor of
prothrombin containing little or no γ-
carboxyglutamate and incapable of
chelating calcium, is released into the
circulation
 Vitamin K Is Also Important in the Synthesis of Bone
Calcium-Binding Proteins

• Treatment of pregnant women with warfarin can

lead to fetal bone abnormalities (fetal warfarin
syndrome)
• Two proteins are present in bone that contain γ-
carboxyglutamate:
1. osteocalcin
2. bone matrix Gla protein
 1 MINUTE QUIZ
• 1. GIVE 3 STATEMENTS THAT SAY “VITAMINS
ARE NOT”
• 2. DISCUSS BRIEFLY DIFFERENCE BETWEEN FAT
SOLUBLE AND WATER SOLUBLE VITAMINS
WITH REGARDS TO DEVELOPMENT OF
TOXICITY
• 3. HOW WILL VITAMIN K COUNTERACT THE
EFFECT OF WARFARIN
WATER SOLUBLE VITAMINS
VITAMIN B FAMILY
VITAMIN C
 THIAMIN
• Thiamin has a central role in energy-yielding
metabolism particularly the metabolism of
carbohydrates
• Thiamin diphosphate is the coenzyme for
oxidative decarboxylation reactions:
1. pyruvate dehydrogenase in carbohydrate
metabolism
2. α-ketoglutarate dehydrogenase in the citric
acid cycle
3. branched-chain keto-acid dehydrogenase
involved in the metabolism of leucine,
isoleucine, and valine
Add: coenzyme for transketolase in the pentose
phosphate pathway
• Thiamin triphosphate has a role in nerve
conduction

• Phosphorylates and activates a chloride

channel in the nerve membrane
 Thiamin Deficiency: Beriberi
Three distinct syndromes:
1. Chronic peripheral neuritis beriberi, which may
or may not be associated with heart failure and
edema
2. Fulminating beriberi (shoshin beriberi) in which
heart failure and metabolic abnormalities
predominate without peripheral neuritis
3. Wernicke encephalopathy with Korsakoff
psychosis which is associated especially with
alcohol and narcotic abuse.
• Thiamin diphosphate deficiency may impair
pyruvate dehydrogenase activity thus
pyruvate cannot be converted to acetyl CoA

• In relatively high carbohydrate diet, this

results in increased plasma concentrations of
lactate and pyruvate, which may cause life-
threatening lactic acidosis.
• Accepted index of thiamin nutritional status:

Erythrocyte transketolase activation by thiamin

diphosphate
 VITAMIN B2 (RIBOFLAVIN)
• A central role in energy
yielding metabolism

• Riboflavin provides the reactive moieties of

(FMN) and (FAD) which are electron carriers
in oxidoreduction reactions
 • Riboflavin deficiency is
widespread but not fatal
• The main dietary
sources of riboflavin: • Efficient storage:
incorporated in enzymes
milk and dairy
products
• Deficiency is
and food additive characterized by cheilosis,
desquamation and
inflammation of the
tongue and a seborrheic
dermatitis
 • Riboflavin nutritional status:
• measurement of the activation of erythrocyte
glutathione reductase by FAD added in vitro
 NIACIN
• It is not strictly a • Two compounds
vitamin: have the biological
synthesized in the activity of niacin
body tryptophan 1. nicotinic acid
• 60 mg of 2. nicotinamide
tryptophan is • as nicotinamide
equivalent to 1 mg ring of the
coenzymes NAD
of dietary niacin and NADP
 • Role: co enzyme

• ADP-ribosylation of proteins and polyADP-

ribosylation of nucleoproteins involved in the
DNA repair mechanism
• Cyclic ADP-ribose • Pellagra is caused by
nicotinic acid adenine deficiency of
dinucleotide: act to tryptophan & niacin
increase intracellular • additional factors:
calcium in response to riboflavin or vitamin B6,
neurotransmitters and deficiency which are
hormones • required for synthesis of
nicotinamide from
tryptophan
 Pellagra can occur
despite an adequate intake of tryptophan
& Niacin
• Hartnup disease - a defect • In carcinoid syndrome,
of the membrane transport there is metastasis of a
mechanism for tryptophan, primary liver tumor of
resulting in large losses as a enterochromaffin cells
result of intestinal
malabsorption and failure • Utilizes as much as 60% of
of renal reabsorption the body’s tryptophan in
the synthesis of 5-
hydroxytryptamine

• Causing pellagra because of

the diversion away from
NAD synthesis.
 • In most outbreaks of pellagra, twice as many
women as men are affected,
• probably the result of inhibition of tryptophan
metabolism by estrogen metabolites
 Niacin is toxic in excess

• 1-6 g/d of nicotinic acid used in

hyperlipidemia cause dilatation of blood
vessels and flushing, along with skin irritation

• Nicotinic acid and nicotinamide in excess of

500 mg/d also cause liver damage.
 VITAMIN B6
• Six compounds with vitamin B6 activity:
1. pyridoxine
2. pyridoxal
3. Pyridoxamine
• and their 5′-phosphates.
4. Pyridoxine phosphate
5. Pyridoxal phosphate
6. Pyridoxamine phosphate
 • About 80% the
body’s total vitamin • Pyridoxal phosphate is not
B6 is pyridoxal available in deficiency
phosphate in muscle
• It is released in starvation,
• mostly associated upon depletion of the
with glycogen glycogen reserves
phosphorylase
• Becomes available in the
liver and kidney for
increased gluconeogenesis
from amino acids
Roles:
• Co factor of glycogen phosphorylase
• Pyridoxal phosphate terminates the action of
the hormones:
(removes the hormone-receptor complex from
DNA binding)
In vitamin B6 Deficiency:

• increased sensitivity to
the actions of
estrogens, androgens, • Moderate deficiency
cortisol, and vitamin D. results in abnormalities
of tryptophan and
• important in the methionine metabolism
development of
hormone-dependent
cancer of the breast,
uterus, and prostate

• vitamin B6 status may

affect the prognosis
Most widely used method of assessing
vitamin B6 status

• activation of erythrocyte transaminases by

pyridoxal phosphate added in vitro, expressed
as the activation coefficient
 TOXICITY
• sensory neuropathy • reports suggest that
reported in patients intakes in excess of 100
taking 2 to 7 g of to 200 mg/d are
pyridoxine per day for associated with
PMS neurological damage
 VITAMIN B12 (COBALAMINS)

• Cobalamin/Corrinoids • Vegans are at risk of

cobalt-containing developing B12 deficiency
compounds possessing the
corrin ring • small amounts formed by
bacteria on the surface of
• FOUND ONLY IN FOODS fruits
OF ANIMAL ORIGIN
• supplement of vitamin
B12 made by bacterial
fermentation
 Vitamin B12 Absorption Requires
Two Binding Proteins
• Vitamin B12 bound to • In the duodenum:
food protein is released cobalophilin is hydrolyzed
by gastric acid and pepsin by pancreatic enzymes
releasing

• Vitamin B12 binds to

cobalophilin Vitamin B12 which binds to
( binding protein secreted intrinsic factor for
in the saliva) absorption
(secreted by the parietal
cells of the gastric mucosa)
 • Vitamin B12 absorption in
the ileum is receptor
• Pancreatic insufficiency mediated
cause vitamin B12
deficiency by the
excretion of cobalophilin- • Receptors bind the
bound vitamin B12 intrinsic factor-vitamin
B12 complex only

• There is considerable
enterohepatic circulation
of vitamin B12
 There Are Two Vitamin B12 Dependent Enzymes

• Methylmalonyl CoA mutase

• activity is reduced in
vitamin B12 deficiency

• accumulation of
methylmalonyl CoA and
urinary excretion of
methylmalonic acid

• which provides a means of

assessing vitamin B12
nutritional status.
 Vitamin B12 Deficiency

• Megaloblastic anemia

• Pernicious Anemia • Spinal cord

degeneration
• The most common
cause of pernicious
anemia:

• failure of the • Result of failure of

absorption of vitamin intrinsic factor secretion
B12 rather than caused by:
dietary deficiency
• autoimmune disease
affecting parietal cells or
from production of anti-
intrinsic factor antibodies
 FOLIC ACID
Multiple forms of folate
in the diet:
• Tetrahydrofolate (THF) • The active form of folic
• 5-Formyl THF acid:
• 10-Formyl THF pteroyl glutamate or
• 5-Formimino THF pteroyl glutamic acid
• 5,10-Methylene THF
• 5-Methyl THF
• 5,10-Methenyl THF
Tetrahydrofolate is a carrier of one-carbon units

The one-carbon fragments • 5-Formyl-

are attached to: tetrahydrofolate is
more stable thus used
• N-5 (formyl, formimino, pharmaceutically
methyl groups) (known as folinic acid)

• N-10 (formyl) • synthetic compound

(leucovorin)

• N-5–N-10 (methylene
or methenyl groups)
 • The methylation of dUMP to
TMP catalyzed by thymidylate
synthase is essential for the
synthesis of DNA
Inhibitors of folate
metabolism are • Methylene-tetrahydrofolate is
used in: used with release of
dihydrofolate which is then
reduced back to
• Cancer tetrahydrofolate by
chemotherapy dihydrofolate reductase
• Antibacterial
• Antimalarial • Thymidylate synthase and
drugs dihydrofolate reductase are
especially active in tissues with
a high rate of cell division
• Methotrexate, an analog of
10-methyl-tetrahydrofolate,
inhibits dihydrofolate
reductase and has been • Antibacterial drug
exploited as an anticancer trimethoprim and
drug antimalarial
drug pyrimethamine are
inhibitors of dihydrofolate
reductase
• Vitamin B12 deficiency
causes functional folate
deficiency—the “folate
trap”
 • When acting as a • Vitamin B12 deficiency
methyl donor, S- results in the
adenosyl methionine accumulation of
forms homocysteine, methyltetrahydrofolate
which is remethylated that cannot be used —
back by the “folate trap.”
methyltetrahydrofolate
catalyzed by methionine
synthase, a vitamin B12
dependent enzyme
 • Folate deficiency • Folic Acid Supplements
causes megaloblastic Reduce the Risk of
anemia Neural Tube Defects
and
• affects cells that are • Hyperhomocysteinemia
dividing rapidly because &
they have a large • May Reduce the
requirement for Incidence of
thymidine for DNA Cardiovascular Disease
synthesis &
• Some Cancers
• Supplements of 400 • Elevated blood
μg/d of folate begun homocysteine is a
before conception significant risk factor for
result in a significant atherosclerosis,
reduction in the thrombosis, and
incidence of spina hypertension
bifida and other neural
tube defects
• Anencephaly
• Folic acid enrichment of foods may put some
people at risk?
 Quiz
1. Briefly explain the absorption of Vit B 12
2. Explain briefly “ folate trap”
3. Explain briefly how carcinoid syndrome cause
pellagra
 DIETARY BIOTIN DEFICIENCY IS UNKNOWN

• Biotin is widely distributed in many foods as

biocytin ( E-amino-biotinyllysine), which is
released on proteolysis.

• Two Forms
• Alpha biotin – abundant in egg yolk
• Beta biotin – abundant in liver
 • Synthesized by intestinal flora in excess of
requirements

• Deficiency is unknown except among people

maintained for many months on total parenteral
nutrition

• Very small number who eat abnormally large

amounts of uncooked egg white, which contains
avidin, a protein that binds biotin and renders it
unavailable for absorption
Biotin Is a Coenzyme of Carboxylase Enzymes

• Acetyl-CoA carboxylase
• Pyruvate carboxylase
• Propionyl-CoA carboxylase
• Methylcrotonyl-CoA carboxylase.

• Biotin also has a role in regulation of the cell

cycle, acting to biotinylate key nuclear proteins.
 PANTHOTENIC ACID

• Essential Component Of Coa, ACP

• Also Called Coaacetylase
• ‘Everywhere Vitamin’
• Richest Known Source – ROYAL JELLY
• Pantothenic acid
acts as the
pantetheine
functional moiety
of coenzyme A or
acyl carrier protein • CoA takes part in reactions
(ACP) of the
• Citric acid cycle
• Fatty acid oxidation
• Acetylations and
Cholesterol synthesis
• ACP participates in fatty
acid synthesis
• The vitamin is widely
distributed in all food-
stuffs, and deficiency
has not been
unequivocally reported
in humans except in
specific depletion
studies.
• Clinical Effects in man produced experimentally
- easy fatigability
- GIT symptoms
- cardiovascular disturbances
- numbness and tingling of extremities
- mental depression
- respiratory infection

• Suggested intake: 100 mg daily

ASCORBIC ACID is a Vitamin for Only Some
Species

• Other animals synthesize it as an

intermediate in the uronic acid
pathway of glucose metabolism
• Humans and other primates, the
guinea pig, bats, birds, and most
fishes and invertebrates – considered
A VITAMIN
 Both ascorbic acid and
dehydroascorbic acid have
vitamin activity
• In those species
for which it is a
vitamin, there is a
block in the
pathway as a
result of absence
of gulonolactone
oxidase
Properties
• very sensitive to oxidation • smoking lowers the blood
thus a very good reducing level
agent • steroids and contraceptives
• rapidly destroyed by alkalies lowers blood level
• drying results to loss of Vit C • facilitate absorption of iron
• pasteurizing milk destroys • potentiates the immune
system
Vit C
• lowers blood clot formation
• used up more rapidly under • regulates cholesterol
stressful conditions metabolism

• urine is the major route of

excretion majorly in the
form of oxalic acid [24-63 %]
Factors that affect Vit C requirement
• severe burns
• surgical procedures
• chronic infection
• bacterial toxins
Vitamin C Is the Coenzyme for Two Groups of
Hydroxylases

1. Copper-containing Hydroxylases
2. Iron- containing Hydroxylases
• Dopamine -hydroxylase is a copper-containing
enzyme involved in the synthesis of the
catecholamines (norepinephrine and
epinephrine), from tyrosine in the adrenal
medulla and central nervous system
 Iron-containing Hydroxylases- protein
modification
• Proline and lysine hydroxylases are required for the
postsynthetic modification of procollagen to collagen

• Proline hydroxylase is also required in formation of

osteocalcin and the C1q component of complement

• Aspartate -hydroxylase is required for the postsynthetic

modification of the precursor of protein C, the vitamin K–
dependent protease that hydrolyzes activated factor V in the
blood-clotting cascade

• Trimethyllysine and -butyrobetaine hydroxylases are

required for the synthesis of carnitine.
 • Major function
= as coenzyme in the
formation of tissue
collagen and
intercellular cement •Deficiency: Scurvy
substance
•Scurvy is characterized
• Basic defect in Vit C by failure in the
deficiency
formation and
= abnormal collagen
formation maintenance of
connective tissues

•Necessary for bone

formation
Clinical manifestations of
Scurvy
• spongy gums, tender and
easily bleed leading
to infections, loosening and • swelling at the ends of
falling of teeth long bones
• decreased ability to - costochondral
combat infection junctions [scorbutic
• rough skin rosary]
• purpura or hematoma on • anemia impaired iron
areas subject to absorption
trauma • easy fatigability,
• internal hemorrhages weakness, aching
bones and joints
defects in skeletal
calcification
• There May Be Benefits from
Higher Intakes of Vitamin C

• >100 mg/day, the body's • Best source: Fresh

capacity to metabolize
vitamin C is saturated and
fruits and vegetables
any further intake is • RDA = 100 mg daily
excreted in the urine
• New researches by
• Increased intakes may be Dr Linus Pauling: 2-9
beneficial by enhancing the grams daily in divided
absorption of iron which
depends on the presence of dosage per day at least
the vitamin in the gut 3 hrs apart
• There is very little
good evidence
that high doses of
vitamin C prevent
the common cold, • Prevents the formation of
although they may cancer causing substances
particularly nitrosamine
reduce the [cured meat, malt
duration and beverages, processed
severity of foods]
symptoms = 1 gram of Vit C can
block nitrosamine
formation
= added to cured meat
• The need varies per individual
• Increased intake in the following
- infection - alcohol
- smoking - advancing age
- drugs - pregnancy
- surgery
- burns
- trauma
MINERALS AND TRACE ELEMENTS
 1. Major components of body molecules
C, H, O, N, S
(obtained through intake of water fat, carbohydrates, proteins)

2. Nutritionally important minerals

Ca, P, Mg, Na K, Cl
(<100 mg/day)

3. Trace elements
Cr, Co, Cu, I, F, Fe, Mn, Mo, Se, Zn

4. Additional elements (non-essential for humans)

Ni, Si, Sn, V, B, Li
Transport and storage require specific binding to
carrier proteins

Transferrin – Fe, Cr, Mn, Zn

Albumin – Cu, Zn
Amino acids – Cu, (Fe)
Trancobaltamin - Co
Globulins - Mn
Normal routes of excretion of trace elements

Bile – Cu, Mn, Cr, Zn,

Urine – Co, Cr, Mo, Zn
Pancreatic juice – Zn
Sweat – Zn
Mucosal cell sloughing – Fe, Zn
 Sodium
• Na+ is the major cation of extracellular fluid.
• Plasma concentration: 135 -145 mmol/L
• ICF concentration: 3-10 mmol/L
• Na+ are important in maintaining and influencing
osmotic balance between cells and the interstitial fluid
• Distribution is mediated by the Na+/K+-ATPase pump

•Assignment: renin-angiotensin-aldosterone mechanism

•Hypernatremia is associated with water depletion
(dehydratation)
• Hyponatremia is associated with excess of
intravascular (and perhaps extravascular) water
• Maintaining electric potential in animal tissues
• Na+ are important in neuron (brain and nerve)
function – action potential
 Potassium

• K+ is the principal cation of the intracellular fluid.

• Plasma concentration: 3.5 – 5.2 mmol/L.
• ICF concentration: 110 -160 mmol/L.
• Key role of K+ in skeletal and smooth muscle
contraction
• The main dietary source is the cellular material we
consume as foodstuffs.
• The concentration of K+ in plasma is influenced by the pH of the
blood (physiological pH 7.4 ± 0.04).

• Alkalosis (pH > 7.44) causes hypokalemia → transient shifting of K+

into cells, presumably by stimulation of the Na-K-ATPase.

• Acidosis (pH < 7,36) causes hyperkalemia → transient shifting of K+

from cells at the expense of H+

• Hyperkalemia produces characteristic electrocardio-graphic changes

(life-threatening effect of K+ excess on the heart).
 • Potassium levels below
3.0 mmol/l cause
• Hypokalemia, the
significant Q-T interval
resting membrane
prolongation with
potential is increased
subsequent risk of
• Muscle cells cannot torsade des pointes,
repolarized ventricular fibrillation
• Symptoms do not and sudden cardiac
generally develop
unless potassium levels
are less than 3.0 mEq/L.
• Hyperkalemia, the resting
membrane potential is
decreased
• Heart: Arrythmia
• Membrane becomes
partially depolarized (shortened QT interval
with inability of the heart
• Initially, increases
muscle to rest between
membrane excitability beats)
Ventricular fibrillation and
• If prolonged, the cell sudden death
membrane will become
more refractory and less
likely to fully depolarize.
 Calcium
• Total content of calcium in
the body is more than 1200
• Normal total calcium of
mg. 2 -2.75 mmol/L
• 99% of total content is (9-10.5 mg/dL)
deposit in bones and teeth,
• 1% in blood and body
• Normal ionized calcium
fluids of 1.1-1.4 mmol/L (4.5-
• Intracellular calcium: 5.6 mg/dL).
- cytosol
- mitochondria
- other microsomes
- regulated by "pumps"
 Calcium metabolism

Multiple biological functions of calcium

Cell signaling
Neural transmission
Muscle function
Blood coagulation
Enzymatic co-factor
Membrane and cytoskeletal functions
Secretion
Biomineralization
• Absorption – duodenum and proximal jejunum.
• Active transport across cells.
• Calcium-binding proteins (calbindins) are synthesized in response
to the action of 1,25-dihydroxycholecalciferol (vitamin D3).

• Parathyroid hormone – also increased intestinal absorption of Ca.

 Absorption is inhibited by:
• oxalates (salts of oxalic
acid)
• phytates (salts of phytic
acid - found in grain
soyabeans)
• phosphates (formation of
insoluble salts)
Recommended daily
• sodium
amount:
• caffein Children to age 11 – 1200 mg/day
From age 11 to 24 – 800 mg/day
From age 24 – 500 mg/day
In woman after menopase – 1500 mg/day
(osteoporosis prevention).
Deficiency - hypocalcemia
o tetany, increased neuromuscular
excitability, neurological disoders.
o Result of vit. D deficiency,
hypoparathyroidism, renal
insuficiency.
o Symptoms are: rickets (children),
osteomatacia (adults)

Toxicity – hypercalcemia (normally does

not to occur)
Hyperparathyroidism, vitamin D
intoxication, cancer.
 Phosphorus metabolism
Major role in structure and
function of all living cells and as a
free ion
Integral part of: Blood phosphate: H2PO4- and HPO42-
o nucleic acids concentration measured as phosphorus:
o nucleotides 2.5 - 4.5 mg/100 ml
o phospholipids
o phosphoproteins Absorption in the jejunum.
o phosphate enzymes Phosphate absorption is regulate by 1,25-
(phosphatases, dihydroxycholecalciferol and parathyroid
pyrophosphatases) hormone.
o skeletal hydroxyapatite -
Ca(PO4)2 or Ca(OH)2 PTH mediates mobilization and deposition of
calcium and phosphate from bone.
Deficiency
Rickets in children, osteomalacia in
adults.
Abnormalities in erythrocytes,
leucocytes, platelets, liver.
Depletion of phosphate occurs as a
result of diminished absorption from
intestine or excessive wasting through
kidney.

Hyperphosphatemia is
associated with renal diseases.
 Magnesium
• Nearly 99% of the total body magnesium is located in bone or the
intracellular space.
• Second plentiful cation of the extracellular fluids.
• Mg is a cofactor of all enzymes involved in phosphate transfer
2+

reactions utilizing ATP

• Required for the structural integrity of numerous intracellular
proteins and nucleic acids.
• A substrate or cofactor for important enzymes such as adenosine
triphosphatase, guanosine triphosphatase, phospholipase C,
adenylate cyclase, and guanylate cyclase.
• A required cofactor for the activity of over 300 other enzymes.
• A regulator of ion channels; an important intracellular signaling
molecule.
• A modulator of oxidative phosphorylation.

Mg2+ is chelated between the beta and gamma

phosphates, diminishes the dense anionic
character of ATP
• Only 1% to 3% of total
intracellular Mg2+ exist as a free
ionized form (conc. 0.5 to 1.0
mmol/l).

• Total cellular concentration can

vary from 5 to 20 mmol/l.

• Intracellular Mg2+ is
predominantly complexed to organic
molecules.
 Effect on central nervous system:
• Certain effects of Mg2+ are similar to Ca2+.
• Increased concentration of Mg2+ cause depression of CNS
• Decreased concentration of Mg2+ cause irritability of CNS

Effect on neuromuscular system:

• Direct depressant effect on skeletal muscles – excess of Mg2+
cause decrease in acetylcholine release by motor nerve impulse.
• The action of increased Mg2+ on neuromuscular function are
antagonized by Ca2+.
• Abnormaly low concentration of Mg2+ in extracellular fluid result in
increased acetylcholine release and increased muscle excitability
(tetany).

Excess of Mg2+ cause vasodilatation.

 Hypomagnesemia cause:

• changes in skeletal and cardiac muscle

• changes in neuromuscular function,
• hyperirritability, psychotic behaviour
• tetany

Hypermagnesemia cause:

• muscle weakness
• hypotension
• ECG changes
• sedation and confusion

Hypermagnesemia is usual due to renal insuficiency.

 Copper
• Cu is an essential nutrient.
• Rapid growth increases Cu
demands in infancy.
• The adult body contains Ceruloplasmin (CP) is a glycoprotein,
approximately 100 mg of copper copper-dependent ferroxidase (95% of
– the highest concentrations are the total copper in human plasma),
in liver, kidney, and hearth. oxidizes Fe2+ to Fe3+ in gastrointestinal
iron absorption mechanism.
• The absorption in
gastrointestinal tract requires a
specific mechanism - metal
binding protein
metallothionein (Cu2+ ions are
highly insoluble).
Model of Cu uptake and metabolism in
hepatocytes:
Cu cross the plasma membrane
through Ctr1 (copper transporter1) or
DMT1 (divalent metal transporter1) to
the trans Golgi network (TGN) by
chaperone Hah1. Chaperone protein
Ccs delivers Cu to cytosolic Cu/Zn
SOD. Cox17 delivers Cu to
mitochondria for cytochrome c
oxidase.

Carrol et all, 2004)

• Cu is an essential cofactor in a number of critical
enzymes in metabolism:
superoxide dismutase (Cu/Zn-SOD)
cytochrome c oxidase (COX)
tyrosinase
monoamino oxidase
lysyloxidase

• Cu metabolism is altered in inflammation, infection, an

cancer.
• In infection, Cu is essential for production of Ile-2 by
activated lymphocytes.
• In cancer, plasma CP is positively correlated with
disease stage.
 Iron
Major function of Fe – oxygen transport by hemoglobin.
Fe2+ and Fe3+ are highly insoluble – special transporter
systems are required.
Food Fe is predominantly in Fe3+, tightly bound to organic
molecules.

Apoferritin assimilates up to 4 300 Fe molecules to form

Fe storage protein – ferritin.

In the retikuloendothelial system ferritin provides an

available storage form for iron.

Apotransferrin (apoTf) – protein, that can bind 2 atoms

of Fe to form transferrin, Fe carrier in plasma.
Food iron is predominantly in the ferric state.
In the stomach, where the pH is less than 4, Fe3+
can dissociate and react with low-molecular weight
compounds such fructose, ascorbic acid, citric acid,
amino acids to form ferric complexes soluble in
neutral pH of intestine fluid.

A protein DMT1 (divalent metal transporter 1),

which transports all kinds of divalent metals, then
transports the iron across the cell membrane of
intestinal cells. These intestinal lining cells can
then store the iron as ferritin.

The transfer of iron from the storage ferritin (as

Fe3+ ) involves reduction to ferrous state – Fe2+ in
order for it to be released from ferritine.

The Fe2+ is subsequently again oxidized by

ferroxidase ceruloplasmin and transported bound to
plasma transferrin to storage sites in the bone
marrow, liver muscle, other tissues.
 Molybdenum
Metal required for the function of the metalloenzymes:
xantine oxydase
aldehyde oxidase
sulfite oxidase

Some evidence that Mo can interfere with Co

metabolism by the diminishing the efficiency of copper
utilization.
(the foot content of Mo is highly dependent upon the
soil type in which the foodstuff are grown).
 Selenium
• an integral component of glutathion peroxidase
(intracellular antioxidant),
• a scavenger of peroxides,
• an essential element for immune function
(selenoproteins).

• Selenoproteins catalyse oxido-reduction reactions,

protective function from oxidative stress (macrophage-
or neutrophil-generated free-radical species, UV in
sunlight.

The foot content of Se is highly dependent upon the soil

type in which the foodstuff are grown.
 Manganese
• High concentration of Mn2+ is present in mitochondria
• Functions as a necessary factor for activation of
glycosyltransferases (enzymes responsible for the
synthesis of oligosaccharides, glycoproteins,
proteoglycans.
• Required for superoxid dismutase activity, for
activity of metalloenzymes:
hydrolases
kinases
decarboxylases
transferases.

Deficiency of Mn extensively reduce glycoprotein and

proteoglycan formation.
 Zinc

Component of zinc metalloenzymes :

carbonic anhydrase
lactate dehydrogenase
glutamate dehydrogenase
alkaline phosphatase
thimidine kinase
matrix metalloproteinases

Gustin – protein in saliva – major role in taste.

Deficiency of Zn has serious consequence :

• failure metabolism of nucleic acids (cell division, growth

and differentiation)
• multisystem disfunction as growth retardation,
hypogonadism, ophtalmologic, gastrointestinal,
neuropsychiatric symptoms.

Zink deficiency in children are marked by poor growth

and impairment of sexual development.
 Chromium
Regulation of glucose metabolism as a component of
glucose tolerance factor (GTF).
GTF increases effect of insulin (by facilitating its binding to
cell receptor site).
Chromium regulates plasma lipoprotein concentration.
Reduces serum cholesterol and serum triglycerides.

Iodine
Iodine is incorporated into thyroid hormones.
Iodine is absorbed in the form of inorganic iodine.
Thyreoperoxidase oxidizes inorganic iodine and oxidized I is
transported to phenyl group of tyrosin of thyroglobulin.
 Fluorine
Inorganic matrix of bone and teeth.
Deficiency – osteoporosis and teeth caries.
 QUIZ- KEEP IT SHORT AND SIMPLE
1. HOW DEFICIENCY OF CHROMIUM RESULT TO INSULIN
RESISTANCE

2. WHY ZINC IS GIVEN AS SUPPLEMENT IN

DIARRHEA AND RESPIRATORY INFECTION

3. WHAT IS THE EFFECT OF HYPOKALEMIA ON

MEMBRANE ACTION POTENTIAL

4. WHAT IS THE EFFECT OF HYPERKALEMIA ON

MEMBRANE ACTION POTENTIAL