LECTURE NOTES MCT 201, Shandele G

MCT 201 Lecture Notes 2022
LEVY MWANAWASA MEDICAL UNIVERSITY

GENERAL AND METABOLIC BIOCHEMISTRY
MCT 201
LECTURE NOTES 2022

BY
SHANDELE GINNETHION
NOTE: This is simply a summary of a few topics covered under general biochemistry. Please
take time to read through and understand the concepts on each topic given.
Biochemistry @ LMMU Page 1

INTRODUCTION:
Biochemistry is a branch of science that investigates the chemical processes within and related to
living organisms. It is a laboratory based science that brings together biology and chemistry.
Biochemistry focuses on processes happening at a molecular level. It focuses on what‟s
happening inside our cells, studying components like proteins, lipids and organelles. It also looks
at how cells communicate with each other, for example during growth or fighting illness.
Medical biochemistry is an essential component of curriculum for all categories of health
professionals. Contemporary Biochemistry plays a crucial role in the Medical field, be it
metabolic pathways, storage diseases, mechanism action of varied biomolecules or inter and
intra cellular communications [1].
This book will introduce you to new ideas and products that are applied to some of the biggest
health problems of today. Our focus will be on human biology and medicine. This is critically
essential for your practice [1].
General objectives:
At the end of this course, you should be able to;

 Think like a medical biochemist.
 Develop essential research and diagnostic skills.
 Apply the aspects of general biochemistry in a clinical set up.
 Use principles of biochemistry to solve clinical complications.

Aim:
The aim of this book is to equip you with the necessary knowledge and skills in medical
biochemistry and its direct application in a clinical set up.
Time Frame:
The study material in this book will be covered in one academic year.
Study Skills :
This book will guide you on the most important aspects of the selected units. You are
advised to focus more on the application aspects of biochemistry than anything else. DO
NOT rush to memorize structures in metabolic biochemistry, instead understand the reason
why each pathway is activated or inhibited at that particular moment. Focus more on
regulation of metabolic pathways and how they are connected to each other. It does not help
to know the structure of an enzyme if you do not understand the role it plays in a pathway.
Focus on what is relevant to your field of study. And that is application.
Need Help?
Feel free to consult whenever necessary. You can also form discussion groups with your
course mates if the Lecturers are not available at that particular moment. For additional
lecture time, we shall also have Online Biochemistry Clinics that will be conducted via a
YouTube Channel called “Biochemistry Clinic”. This channel will be addressing most of
your concerns via video lectures that will be posted on demand.

Assessment:
 You will be required to write Three Tests and One quiz making up the 40% for the
continuous assessment.
 At the end of year, you will be required to write a theory final examination making
up for the remaining 60%.
Continuous assessments= 40%

 Three tests=30%
 One Quiz =10%
Theory Examination= 60%
Prescribed and recommended readings:
1. Blanco, A.; Blanco, G. Medical Biochemistry; 2017; ISBN 9780128035870.
2. Echten-deckert, G. Van Biochemistry Metabolic pathways. 2012.
3. Vasudevan, D.; S, S.; Vaidyanathan, K. Textbook of Biochemistry; 2011; ISBN

9789350250167.

UNIT 1: CELLS
Unit Objectives:
At the end of this unit, you must be able to:
 Define a cell.
 Discuss the functions of cell organelles.
 Outline the different mechanisms of membrane transport.
All organisms are composed of structural and functional units of life called „cells‟. The body of
some organisms like bacteria, protozoans and some algae is made up of a single cell whereas the
body of higher organisms such as fungi, plants and animals are composed of many cells. Cells
vary in size and structure as they are specialized to perform different functions. But the basic
components of the cell are common to all biological cells, [2]. A cell may be defined as a unit of
protoplasm bound by a plasma or cell membrane and possessing a nucleus. Protoplasm is the life
giving substance and includes the cytoplasm and the nucleus. The cytoplasm has in it organelles
such as ribosomes, mitochondria, golgi bodies, plastids, lysosomes and endoplasmic reticulum.
Plant cells have in their cytoplasm, large vacuoles containing non-living inclusions like crystals,
and pigments. The bacteria have neither defined cell organelles nor a well formed nucleus. But
every cell has three major components:
(i) Plasma membrane
(ii) Cytoplasm
(iii) DNA (naked in bacteria) and enclosed by a nuclear membrane in all other organisms.

NOTE: “Recall the structure and functions of cell organelles from elementary biology”
For example:
1. Ribosomes: are sites for protein synthesis.

The ribosome, one of the largest molecular machines in living cells, is in charge of protein
synthesis. The ribosome translates genetic code into amino acid sequences that fold into protein
structures. Ribosomes are the birth place of proteins in living cells. The bacterial ribosome plays
also a key role in medicine as a drug target for antibiotics. Antibiotics are employed by
biological cells, for example those arising in molds, to fight bacteria. The most famous antibiotic,
discovered by accident in 1928 by Alexander Fleming, is pencillin, which prevents growing
bacteria from properly building their cell wall. As bacterial cell walls differ dramatically from
the cell membranes of human cells, penicillin fights bacteria without undue side effects on
humans. Unfortunately, bacteria become resistant to antiobiotics and constantly new antibiotics
need to be invented. Here it helps ribosomes that arise in all living cells differ sufficiently
between their bacterial and human varieties such that antibiotics can negatively affect bacterial
ribosomes, but not human ribosomes. Much of modern research on ribosomes is therefore
justified by the perpetual need to develop new antibiotics[3].
2. Cytoplasm: Allows movement of materials built inside the cell. It is a medium for the
organelles to sit/float in[4].
The cytoplasm is the part of the cell located outside the nucleus filling the space
between nuclear envelop and plasma membrane. It consists of:
 Cytosol is a large fluid component of the cytoplasm.

 Organelles (“little organs”) are swimming metabolically active structures, which may be
membranous (such as mitochondria) or non-membranous protein complexes (such as
ribosomes and proteasomes).

 Cytoskeleton is protein component of the cytoplasm which determine the shape and
motility of eukaryotic cells.
 Inclusions are the minor cytoplasmic structures that are not usually surrounded by a
membrane. They consist of such diverse materials like crystals, pigment granules, lipids,
glycogen, and other stored waste products.
3. Cytosol
 Cytosol is an aqueous gel called the cytoplasmic matrix. The matrix consists of a variety
of solutes, including inorganic ions (Na+, K+, and Ca2+) and organic molecules such as
intermediate metabolites, carbohydrates, lipids, proteins, and RNAs (ribonucleic acids).
The cell controls the concentration of solutes within the matrix, which influences the rate
of metabolic activity within the cytoplasmic compartment. Cytosol also contains
hundreds of enzymes, all the machinery converging on the ribosomes for protein
synthesis, O2, CO2, electrolytic ions, low-molecular-weight substrates, metabolites, and
waste products. All diffuse through cytosol, either freely or bound to proteins, entering or
leaving organelles where they are used or produced.
 Cytoplasmic Organelles
All cells have the same basic set of intracellular organelles, which can be classified
into two groups:
1. Membranous organelles with membranes that separate the internal environment of the
organelle from the cytoplasm.
2. Non membranous organelles without membranes. The membranes of membranous
organelles form vesicular, tubular, and other structural patterns within the cytoplasm that
may be convoluted (as in smooth surfaced endoplasmic reticulum) or plicated (as in the
inner mitochondrial membrane). In addition, each type of organelle contains a set of
unique protein.
 In membranous organelles, these proteins are either incorporated into their membranes or
sequestered within their lumens. For example, the enzymes of lysosomes are separated by a
specific enzyme resistant membrane from the cytoplasmic matrix because their hydrolytic
activity would be harmful to the cell. In Non membranous organelles, the unique proteins
usually self assemble into polymers that form the structural elements of the cytoskeleton .

4. Nucleus: Is Control center, Stores the cell’s DNA and controls different activities in
the cell.
The nucleus, which has a diameter of about 5 m, is a prominent structure in the eukaryotic cell.
The nucleus is of primary importance because it stores the genetic material DNA which governs
the characteristics of the cell and its metabolic functioning. Every cell in the same individual
contains the same DNA, but, in each cell type, certain genes are turned on and certain others are
turned off. Activated DNA, with RNA acting as an intermediary, specifies the sequence of amino
acids when a protein is synthesized. The proteins of a cell determine its structure and the
functions it can perform. When you look at the nucleus, even in an electron micrograph, you
cannot see a DNA molecule. You can see chromatin, which consists of DNA and associated
proteins[5]
5. Mitochondria: Cell Powerhouse and site of Cellular Respiration. Makes “ATP”

Mitochondria are the powerhouses of the cell. In all eukaryotes that do not depend on
photosynthesis, the mitochondria are the main source of adenosine triphosphate (ATP), the
energy-rich compound that drives fundamental cell functions. These functions include force
generation (for example, in muscle contraction and cell division), the biosynthesis, folding and
degradation of proteins, and the generation and maintenance of membrane potentials. ATP is
produced on a massive scale in the human body, amounting to 50 kg per day in a healthy adult,
but considerably more in a long-distance runner. ATP is generated by the mitochondrial ATP
synthase from ADP and phosphate ions. These are the products of ATP hydrolysis at the sites
where energy is needed in the cell. Apart from cellular respiration and ATP synthesis,
mitochondria have numerous other essential functions, including the production of NADH and
GTP in the citric acid cycle, the biosynthesis of amino acids, heme groups and iron-sulfur
clusters or the synthesis of phospholipids for membrane biogenesis. They also act in calcium

signaling, stress responses and generally as cellular signaling hubs. Not surprisingly,
mitochondria play a fundamental role in human health. Mitochondrial dysfunction is the cause of
severe, often maternally inherited diseases. Moreover, mitochondria are deeply implicated in
apoptosis and ageing.
6. ER: Transport and storage of proteins and lipids

The endoplasmic reticulum (ER), a complicated system of membranous channels and saccules
(flattened vesicles), is physically continuous with the outer membrane of the nuclear envelope.
Rough ER is studded with ribosomes on the side of the membrane that faces the cytoplasm.
Here, proteins are synthesized and enter the ER interior, where processing and modification
begin. Most proteins are modified by the addition of a sugar chain, which makes them a
glycoprotein. Smooth ER, which is continuous with rough ER, does not have attached
ribosomes. Smooth ER synthesizes the phospholipids that occur in membranes and has various
other functions depending on the particular cell. In the testes, it produces testosterone, and in the
liver, it helps detoxify drugs. Regardless of any specialized function, smooth ER also forms
vesicles in which proteins are transported to the Golgi apparatus. ER is involved in protein
synthesis (rough ER) and various other processes, such as lipid synthesis (smooth ER). Vesicles
transport proteins from the ER to the Golgi apparatus.
7. Golgi bodies: Is the packaging center of the cell

The Golgi apparatus is named for Camillo Golgi, who discovered its presence in cells in 1898.
The Golgi apparatus consists of a stack of three to twenty slightly curved saccules whose
appearance can be compared to a stack of pancakes. In animal cells, one side of the stack (the
inner face) is directed toward the ER, and the other side of the stack (the outer face) is directed
toward the plasma membrane. Vesicles can frequently be seen at the edges of the saccules.
The Golgi apparatus receives protein and also lipid filled vesicles that bud from the smooth ER.
These molecules then move through the Golgi from the inner face to the outer face. How this

occurs is still being debated. During their passage through the Golgi apparatus, glycoproteins
have their sugar chains modified before they are repackaged in secretory vesicles. Secretory
vesicles proceed to the plasma membrane, where they discharge their contents. Because this is
secretion, the Golgi apparatus is said to be involved in processing, packaging, and secretion.
The Golgi apparatus is also involved in the formation of lysosomes, vesicles that contain proteins
and remain within the cell.
Lysosomes
Lysosomes are membrane-bounded vesicles produced by the Golgi apparatus. Lysosomes
contain hydrolytic digestive enzymes. Sometimes macromolecules are brought into a cell by
vesicle formation at the plasma membrane. When a lysosome fuses with such a vesicle, its
contents are digested by lysosomal enzymes into simpler subunits that then enter the cytoplasm.
Some white blood cells defend the body by engulfing pathogens by vesicle formation. When
lysosomes fuse with these vesicles, the bacteria are digested. Even parts of a cell are digested by
its own lysosomes (called autodigestion). Normal cell rejuvenation takes place in this manner.
Lysosomes contain many enzymes for digesting all sorts of molecules. Occasionally, a child
inherits the inability to make a lysosomal enzyme, and therefore has a lysosomal storage disease.
Instead of being degraded, the molecule accumulates inside lysosomes, and illness develops
when they swell and crowd the other organelles. In Tay Sachs disease, the cells that surround
nerve cells cannot break down a particular lipid, and the nervous system is affected. At about six
months, the infant can no longer see and, then, gradually loses hearing and even the ability to
move. Death follows at about three years of age.
Cell Membrane:
The plasma membrane is made of proteins and lipids and several models were proposed
regarding the arrangement of proteins and lipids. The fluid mosaic model proposed by Singer
and Nicholson (1972) is widely accepted.
 The plasma membrane is composed of a lipid bilayer of phospholipid molecules into

which a variety of globular proteins are embedded.

 Each phospholipid molecule has two ends, an outer head hydrophilic i.e. water attracting,
and the inner tail pointing centrally hydrophobic, i.e. water repelling.
Functions of Membrane:
The plasma membrane encloses the cell contents. It provides cell shape (in animal cells) e.g. the
characteristic shape of red blood cells, nerve cells, and bone cells. It allows transport of certain
substances into and out of the cell but not all substances so much it is termed „selectively
permeable ‟. Small molecules can be transported across the plasma membrane by any one of the
following three methods:
Diffusion:
 Molecules of substances move from their region of higher concentration to the regions of
lower concentration. This does not require energy. Example: absorption of glucose in a
cell.
Osmosis:
 Movement of water molecules from the region of their higher concentration to the region
of their lower concentration through a semipermeable membrane. There is no expenditure
of energy in osmosis. This kind of movement is along concentration gradient.
Active Transport:
 When the direction of movement of a certain molecule is opposite to that of diffusion i.e.
from region of their lower concentration towards the region of their higher concentration,
it would require an “active effort” by the cell for which energy is needed. This energy is
provided by ATP (adenosine triphosphate). The active transport may also be through a
carrier molecule.
Membrane Transport:
Life depends on a membrane's ability to precisely control the level of solutes in the aqueous
compartments, inside and outside the membrane. The membrane determines what solutes enter
and leave a cell. Trans-membrane transport is controlled by complex interactions between
membrane lipids, proteins, and carbohydrates.
Simple Passive Diffusion:
Movement of solutes across membranes can be divided into two basic types: passive diffusion
and active transport. Passive diffusion requires no additional energy source other than what is
found in the solute's electrochemical (concentration) gradient and results in the solute reaching
equilibrium across the membrane.
Passive diffusion can be either simple passive diffusion where the solute crosses the membrane
anywhere by simply dissolving into and diffusing through the lipid bilayer, or facilitated passive
diffusion where the solute crosses the membrane at specific locations where diffusion is assisted
by solute-specific facilitators or carriers.
Active transport requires additional energy, often in the form of ATP, and results in a non-
equilibrium, net accumulation (uptake) of the solute on one side of the membrane. The basic
types of membrane transport, simple passive diffusion, facilitated diffusion (by channels and
carriers) and active transport are summarized. There are countless different examples of each
type of membrane transport process. Only a few representative examples will be discussed here.

Figure 1: Passive transport vs active transport
Facilitated Passive Diffusion:
Facilitated diffusion (also known as carrier-mediated diffusion) is, like simple passive diffusion,
dependent on the inherent energy in a solute gradient. No additional energy is required to
transport the solute and the final solute distribution reaches equilibrium across the membrane.
Facilitated diffusion, unlike simple passive diffusion, requires a highly specific trans-membrane
integral protein or carrier to assist in the solute's membrane passage. Facilitators come in two
basic types: carriers and gated channels.
Active Transport:
A characteristic of all living membranes is the formation and maintenance of trans-membrane

gradients of all solutes including salts, biochemicals, macromolecules, and even water. In living
cells, large gradients of Na+ and K+ are particularly important. Typical cell concentrations are:
Primary Active Transport:
Primary active transport is also called direct active transport or uniport. It involves using energy
(usually ATP) to directly pump a solute across a membrane against its electrochemical gradient.
The most studied example of primary active transport is the plasma membrane Na+,K+-ATPase.
Secondary Active Transport:
Secondary active transport (also known as cotransport) systems are composed of two separate
functions. The energy-dependent movement of an ion (eg, H+, Na+, or K+) generates an
electrochemical gradient of the ion across the membrane. This ion gradient is coupled to the

movement of a solute in either the same direction (symport) or in the opposite direction (antiport,
Movement of the pumped ion down its electrochemical gradient is by facilitated diffusion.
Further Membrane Transport:
Two similar transport processes that have been known for a long time are pinocytosis and
phagocytosis. Both involve nonspecific uptake (endocytosis) of many things from water and ions
through to large macromolecules and, for phagocytosis, even whole cells. Pinocytosis is Greek
for “cell drinking”! Pinocytosis is a form of endocytosis involving fluids containing many
solutes. In humans, this process occurs in cells lining the small intestine and is used primarily for
absorption of fat droplets. Phagocytosis is a type of endocytosis that involves uptake of large
solid particles. The particles are aggregates of macromolecules, parts of other cells, and even
whole microorganisms and, in contrast to pinocytosis, phagocytosis has surface proteins that
specifically recognize and bind to the solid particles. Exocytosis is the process by which cells
excrete waste and other large molecules from the cytoplasm to the cell exterior and therefore is
the opposite of endocytosis. Exocytosis generates vesicles referred to as secretory or transport
vesicles.
Quick Thoughts:
1. What do you think is the biochemical importance of giving Oral Rehydration Therapy
in individuals with diarrhea? Explain your answer using principles of osmosis and
diffusion.
2. Describe the mechanism used to move across the cell membrane by the end-products
of protein digestion in human beings.
UNIT 2: WATER AND BIOMOLECULES
Unit Objectives:

At the end of this unit, you should be able to:
 Define water and mention its properties

 Discuss the importance of the unique properties of water
 Describe the medical applications of water properties
Water is a molecule made up of two hydrogen atoms and one oxygen atom. It has the formula
H2O. When oxygen and hydrogen combine (H-O-H) they form a v-shaped triangular molecule.
While water molecules are electrically neutral, the oxygen atom holds a small negative charge
and the two hydrogen atoms hold small positive charges. Water molecules are attracted to each
other, creating hydrogen bonds. Hydrogen bond is a weak attraction between a hydrogen atom
and other atom. These bonds determine almost every physical property of water and many of its
chemical properties too. Water is the mediator of chemical and biochemical processes. Water
shapes our natural environment and even mediates our climate and weather[6]
Surface Tension:
Water molecules at the surface (next to air) hold closely together, forming an invisible film.
Water‟s surface tension can hold weight that would normally sink. You can carefully float a
paper clip on top of the water. Some aquatic insects such as the water strider or pond skater rely
on surface tension to walk on water. Surface tension is essential for the transfer of energy from
wind to water to create waves. Water is Sticky Cohesion: water molecules stick to each other.
This is due to the hydrogen bonds among the molecules. Water molecules at the surface have a
much greater attraction for each other than for molecules in the air. This cohesiveness creates a
high surface tension at the surface of the water.
The water molecules at the surface crowd together, producing a strong layer as they are pulled
downward by the attraction of other water molecules beneath them.

Adhesion: Water molecules stick to other substances. You can see this property when water
creeps up the inside of a drinking glass. Think of a sponge or a paper towel used to “soak up”
spilled water. This is how water makes things wet. Water also clings to living things.
Thermal Properties
Water absorbs or releases more heat than many substances for each degree of temperature
increase or decrease. Because of this, it is widely used for cooling and for transferring heat in
thermal and chemical processes. Differences in temperature between lakes and rivers and the
surrounding air may have a variety of effects. Large bodies of water, such as the oceans or the
Great Lakes, have a profound influence on climate.
Specific Heat:
Water has a high specific heat. The amount of energy required to raise the temperature of water
by one degree Celsius is quite large. Because so much heat loss or heat input is required to lower
or raise the temperature of water, the oceans and other large bodies of water have relatively
constant temperatures. Thus, many organisms living in the oceans are provided with a relatively
constant environmental temperature.
Heat of Vaporization:
Water has a high heat of vaporization. Water absorbs heat as it changes from a liquid to a gas;
the human body can dissipate excess heat by the evaporation of its sweat. A leaf can keep
cool in the bright sunlight by evaporating water from its surface. Water‟s high heat conductivity
makes possible the even distribution of heat throughout the body. This is why it takes longer to

boil and egg at higher altitudes. The temperature does not get high enough to cook the egg
properly. If a substance is dissolved in water, then the freezing point is lowered. That is why we
spread salt on streets in winter to prevent ice formation, [7].
TAKE NOTE:
 Pure water has a pH of 7, which is neutral, which indicates that it has exactly the same
number of H+ (hydrogen) ions as OH- (hydroxide) ions floating in solution. If there are
relatively more H+ ions, the pH decreases, increasing the acidity. More H+, more
acidic, lower pH.If there are relatively less H+ ions, the pH increases, increasing the
basicity. Less H+, more basic, higher pH.
Quick Thought:
One of the most critical properties of water is the formation of Hydrogen Bonds, Using as much
biochemical principles as possible, outline the importance of this property of water in your field
of study.
UNIT 3: CHEMISTRY OF CARBOHYDRATES:
Unit Objectives:
At the end of this unit you should be able to:
 Describe the different classes of carbohydrates

 Understand the meaning of enantiomers, anomers, epimers and chiral centres
 Discuss the importance of the common monosaccharides, disaccharides and
polysaccharides
Carbohydrates are the most abundant organic molecules in nature, [8]. They can simply be
referred to as, the “hydrates of carbon.” “Carbo”: comes from the word “carbon” and
“hydrate” from the word “hydration”. Many, but not all, carbohydrates have the empirical
formula (CH2O)n. There are four major size classes of carbohydrates:

 monosaccharides, disaccharides, oligosaccharides, and polysaccharides.

Functions Of Carbohydrates:
Certain carbohydrates (sugar and starch) form dietary staple, and the oxidation of carbohydrates
is the central energy-yielding pathway. These sugars provide the body with energy when
consumed. In this case, glucose is the primary carbohydrate used by our bodies. Insoluble
carbohydrate polymers serve as structural and protective elements in the cell walls of bacteria,
yeasts (dextran) and plants (cellulose).
Monosaccharides:
Mono”-means “one!” “Saccharide”-means “sugar!” They are simple sugars. The most abundant
monosaccharide in nature is D-glucose, sometimes referred to as dextrose. They may be
classified as trioses, tetroses, pentoses, hexoses, or heptoses, depending upon the number of
carbon atoms.
 The simplest monosaccharides of biological significance are trioses glyceraldehyde and

dihydroxyacetone. Refer to the diagram below:
Figure 2: The three carbon sugars
The ALDOSE SUGARS!

Figure 3: Aldose Sugars
The KETOSE SUGARS!

Figure 4: Ketose sugars
What major differences can you see between the aldose sugars and the ketose sugars?
 After critical analysis of both groups of sugars you will notice that the carbonyl group
forms carbon 1 of aldose sugars where as in ketose sugars it forms at carbon 2
Chiral Centres:

All the monosaccharides except di-hydroxy-acetone contain one or more asymmetric (chiral)
carbon atoms and thus occur in optically active isomeric forms, called enantiomers. When a
carbon atom is linked to four different groups it is referred to as a chiral carbon.
How many chiral carbons can you see in the diagrams below?
Figure 5: Chiral Carbon
The stereoisomers of monosaccharides of each carbon-chain length can be divided into two
groups that differ in the configuration about the chiral center most distant from the carbonyl
carbon. If the –OH group at this chiral center is on the right, then the sugar is said to have the D-
configuration and if the –OH group is on the left, the configuration is L. Check out the table
below:
O H O H
C C
H – C – OH HO – C – H
HO – C – H H – C – OH
H – C – OH HO – C – H
H – C – OH HO – C – H
CH2OH CH2OH
D-glucose L-glucose
Figure 6: Enatiomeric forms
Epimers:

Two sugars that differ only in the configuration around one carbon atom are called epimers. D-
glucose and D-mannose, which differ only in the stereochemistry at C-2, are epimers, as are D-
glucose and D-galactose.
Figure 7: Epimeric forms
Anomers:
Isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or
hemiketal carbon atom are called anomers. The hemiacetal (or carbonyl) carbon atom is called
the anomeric carbon.For instance, the α and β anomers of D-glucose interconvert in aqueous
solution by a process called mutarotation.

Figure 8: Anomeric forms
and
Thus, a solution of α-D-glucose and a solution of β -D-glucose eventually form identical

equilibrium mixtures having identical optical properties. Ketohexoses also occur in α and β
anomeric forms. In these compounds the hydroxyl group at C-5 reacts with the keto group at C-
2, forming a furanose (or pyranose) ring containing a hemiketal linkage. D-Fructose readily
forms the furanose ring.
Disaccharides:
Disaccharides are condensation products of two monosaccharide units. Examples are maltose,
lactose and sucrose.The disaccharide lactose, which yields D-galactose and D-glucose on

hydrolysis, occurs naturally only in milk. The anomeric carbon of the glucose residue is
available for oxidation, and thus lactose is a reducing disaccharide.
Sucrose (table sugar) is a disaccharide of glucose and fructose. It is formed by plants but not by
animals. Sucrose contains no free anomeric carbon atom; the anomeric carbons of both
monosaccharide units are involved in the glycosidic bond). Sucrose is therefore a non-reducing
sugar.
Polysaccharides:
Most carbohydrates found in nature occur as polysaccharides, also called glycans.
 Homopolysaccharides: contain only a single type of monomer;

 Heteropolysaccharides: contain two or more different kinds.
Some homopolysaccharides serve as storage forms of monosaccharides that are used as fuels.
(starch & glycogen). Other homopolysaccharides (cellulose and chitin, for example) serve as
structural elements in plant cell walls and animal exoskeletons.

Homopolysaccharides:
The most important storage polysaccharides are starch in plant cells and glycogen in animal
cells. Both polysaccharides occur intracellularly as large clusters or granules. Starch and
glycogen molecules are heavily hydrated, because they have many exposed hydroxyl groups
available to hydrogen-bond with water.
Starch:
Found in in tubers, such as potatoes, and in seeds. It contains two types of glucose polymer,
amylose and amylopectin. Amylose consists of long, unbranched chains of D-glucose residues
connected by (α1,4) linkages. Amylopectin is highly branched. The glycosidic linkages joining
successive glucose residues (α1,4); the branch points (occurring every 24 to 30 residues) are (α1,
6) linkages.
Figure 9: starch

Glycogen:
Glycogen is the main storage polysaccharide in animal cells. It is a polymer of (α1, 4)-linked
subunits of glucose, with (α1, 6) linked branches, but glycogen is more extensively branched (on
average, every 8 to 12 residues) and more compact than starch. Glycogen is especially abundant
in the liver; it is also present in skeletal muscle. In hepatocytes glycogen is found in large
granules.

Quick Thoughts:
 Maltose and Sucrose are both disaccharides, give a detailed biochemical reason why one
is a reducing sugar and the other non-reducing sugar.
 Using as many examples as possible, explain the difference between enantiomers and
epimers

UNIT 4: CHEMISTRY OF LIPIDS
Unit Objectives:
At the end of this unit, you should be able to;
 Define lipids
 Describe the different classes of lipids
 Explain the difference between saturated and unsaturated fatty acids
 Discuss the importance of lipids
Lipids are a heterogeneous group of water insoluble organic molecules that can be extracted
from tissues by non-polar solvents. The list includes fats, oils, steroids, waxes, and related
compounds[9][10]. Lipids play critical roles in living things. It is therefore necessary to analyze
these functions of lipids. They provide the hydrophobic barriers permitting partitioning of
aqueous contents of cells and sub cellular structures. Lipids also shape and contour to the body
and protect internal organs by providing a cushioning effect. They also serve as a thermal
insulator in the subcutaneous tissues and around certain organs.
Classes of Lipids:
Simple Lipids:
Simple Lipids are esters of fatty acids with various alcohols. Examples are given below!
 Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state.
 Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols
Compound Lipids:
Compound lipids are esters of fatty acids containing groups in addition to an alcohol and a fatty
acid.

 Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric

acid residue.
 Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and
carbohydrate.
Precursor & derived lipids:
These include fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, and ketone bodies,
hydrocarbons, lipid-soluble vitamins, and hormones. Because they are uncharged, acyl-glycerols
(glycerides), cholesterol, and cholesterol esters are termed neutral lipids.
Fatty acids:
Fatty acids are chains of carbon atoms with a carboxyl group at one end, and a methyl group at
the other. Carbon atoms are numbered from the carboxyl carbon. The chain may be saturated
(containing no double bonds) or unsaturated (containing one or more double bonds).
STRUCTURE:
Figure 10: Fatty acid structure

Unsaturated Fatty Acids:
Monounsaturated: These acids contain only one double bond in the structure.
Polyunsaturated: These acids contain two or more double bonds
Unsaturated fatty acids do not stack compactly and are liquid at room temperature. A cis double
bond forms a kink in the hydrocarbon chain. Molecules cannot pack as tightly as fully saturated
fatty acids and their interactions with each other are weaker.
Saturated Fatty Acids:
Long-chain saturated fatty acids stack tightly and form solids at room temperature. Molecules
can pack in crystalline arrays with atoms all along their lengths in contact with atoms of
neighbouring chains. Storage lipids are more saturated.

Dietary Implications:
Naturally occurring unsaturated long-chain fatty acids are nearly all of the cis-configuration.
Trans-fatty acids are produced by fermentation in the rumen of dairy animals and are obtained
from dairy products and meat. They are also produced during hydrogenation of fish or vegetable
oils (to produce margarine). Diets high in trans-fatty acids correlate with increased blood levels
of LDL (bad cholesterol) and decreased HDL (good cholesterol).
BAD CHOLESTEROL:
 Known as “bad cholesterol” because they can transport their content of fat molecules into
artery walls, attract macrophages, and thus cause atherosclerosis.
GOOD CHOLESTEROL:
 Known as “good cholesterol” because it removes fat and cholesterol from cells, including
within artery wall, and transport it back to the liver for excretion or re-utilization.
Tri-acyl-glycerols (TAG) – Also known as neutral fats, or triglycerides (TG). This has three fatty
acids attached to a glycerol backbone. There are two significant advantages for using
triacylglycerols as stored fuels rather than polysaccharides such as glycogen or starch. Carbon
atoms of fatty acids are more reduced than those of sugars, oxidation of triacylglycerols yields
much more energy per gram, compared to oxidation of carbohydrates. Triacylglycerols are
hydrophobic and therefore unhydrated: no extra weight of water that is associated with stored
polysaccharides. Energy needs can be met for months by drawing on fat stores. Human body can
store less than a day‟s energy supply in the form of glycogen.

Figure 11: Triglyceride structure
 The simple triglycerides contain the same type of fatty acid residue at all three carbons.
 Mixed triglycerides contain 2 or 3 different types of fatty acid residues. These are more
common.
Properties of fatty acids:
Hydrolysis:
This is simply the splitting of a compound using water. They undergo stepwise enzymatic
hydrolysis to liberate free fatty acids and glycerol. This simply means each fatty acid is liberated
at each step. The enzymes responsible for this catalysis is called LIPASE.

UNIT 5: ENZYMOLOGY :
Unit Objectives:
At the end of this unit, you should be able to;
 Define enzymes
 Describe enzyme activity
 Explain the mechanisms of enzyme action
 Discuss the applications of enzymes in medicine
Enzymes are biological polymers that catalyze the chemical reactions which make life as we
know possible. The presence and maintenance of a complete and balanced set of enzymes is
essential for;
(i) the breakdown of nutrients to supply energy and chemical building blocks;
(ii) the assembly of those building blocks into proteins, DNA, membranes, cells, and
tissues; and
(iii) the harnessing of energy to power cell motility and muscle contraction.
With the exception of a few catalytic RNA molecules, or ribozymes, the vast majority of
enzymes are proteins. Their catalytic activity depends on the integrity of their native protein
conformation. Deficiencies in the quantity or catalytic activity of key enzymes can result from
genetic defects, nutritional deficits, or toxins.
 Substances on which enzymes act to convert them into products are called substrates.
 For chemical reaction to take place, the reacting molecules are required to gain a
minimum amount of energy, called energy of activation.
 Enzymes have immense catalytic powers and accelerate reactions at least a million times
by reducing the energy of activation. Few enzymes are simple proteins while some are
conjugated proteins. In such enzymes the non-protein part is called prosthetic group or
coenzyme and the protein part is called apoenzyme.

 When many different enzyme catalyzing sites are located at different sites of the same
macromolecule, it is called multienzyme complex. Examples: fatty acid synthase,
carbamoyl phospahte synthetase II, pyruvate dehydrogenase, etc. The complex becomes
inactive when it is fractionated into smaller units each bearing individual enzyme
activity.
COENZYMES
 Certain enzymes require non-protein organic coenzymes for the activity.

 Prosthetic groups are distinguished by their tight, stable incorporation into a protein‟s
structure by covalent or non-covalent forces. Examples include Biotin, tertrahydrofolate,
NAD+, NADP, FMN, FAD, Co, Cu, Zn etc. Enzymes that contain tightly bound metal
ions are termed metalloenzymes.
COFACTORS
 Cofactors serve functions similar to those of prosthetic groups but bind in a transient,
dissociable manner either to the enzyme or to a substrate.
 Cofactors must be present in the medium surrounding the enzyme for catalysis to occur.
 Enzymes that require a metal ion cofactor are termed metal-activated enzymes.
Nomenclature of Enzymes:
The International Union of Biochemistry (IUB) adopted a nomenclature system based on

chemical reaction type and reaction mechanism.The systemic names for enzymes include the
substrate and the type of reaction. According to this system, enzymes are grouped into six main
classes. They are:
1. Oxidoreductase: catalyze oxidations - reductions of their substrates, e.g. alcohol

dehydrogenase, lactate dehydrogenase.
2. Transferase: catalyze transfer of particular group from one substrate to another, e.g.
hexokinase, aspartate and alanine transaminase (AST/ALT).

3. Hydrolase: bring about hydrolysis, the addition of water to a chemical bond. e.g.
glucose-6-phospatase, pepsin, trypsin.
4. Lyases: usually catalyze a carbon-carbon bond cleavage., e.g. fumarase, arginosuccinase.
5. Isomerases: transfer of groups or bonds within molecules to yield isomeric forms, e.g.
UDP-glucose, epimerase.
6. Ligases: catalyze joining together two substrates coupled with ATP hydrolysis, e.g. DNA
ligase, glutamine synthetase.
Enzyme Specificity:
An important property of enzyme is their specificity. Specificity is of 4 different types;
1. Optical specificity:
 Substrates can have optical isomers, but only one of the isomers acts as a substrate for the
enzyme activity.
2. Reaction specificity:
 An enzyme can catalyze only a single type of reaction. A substrate can undergo many
reaction, each reaction catalyzed by different enzymes.
3. Substrate specificity:
 This means that certain enzymes are specific for a certain substrate.
 Substrate specificity is of two type; group dependent and bond dependent.
4. Group specificity:
The enzyme will act only on molecules that have specific functional groups, such as amino,
phosphate and methyl groups. E.g. Trypsin hydrolyses the residues of only lysine and
arginine, chymotrypsin hydrolyses residues of only aromatic amino acids.
5. Bond specificity

The enzyme will act on a particular type of chemical bond regardless of the rest of the
molecular structure. E.g. Proteolytic enzymes, glycosidases and lipases act on peptide,
glycosidic and ester bonds respectively.
Mechanism of Enzyme Action:
According to most acceptable hypothesis, enzyme molecule (E) first combines with substrate
molecule (S) to form an enzyme-substrate (ES) complex which further dissociates to form
product (P) and enzyme (E), [11]. Enzyme once dissociated from ES complex is free to combine
with another substrate and form product. The ES complex is an intermediate or transient
complex held together by weak non-covalent bonds such as H-bonds, Van der Waals forces,
hydrophobic interactions. The site at which the substrate can bind to the enzyme with extreme
specificity is called active site or catalytic site. The active site is made up of several amino acids
that come together as a result of folding of secondary and tertiary structures of the enzyme.
MODELS
1) Template or Lock and Key Model
 This model states that the active site already exists in proper conformation even in the
absence of the substrate. The active site provides a rigid, pre-shaped template fitting with
the size and shape of the substrate molecule. Substrate fits into the active site as key fits
into lock, hence called lock and key model. Model cannot explain change in enzyme
activity in presence of allosteric modulators.
2) Induced Fit or Koshland Model
 Important feature of this model is the flexibility of active site region.

 According to this, the substrate during its binding induces conformational changes in the
active site to attain the final catalytic shape and form.
Factors affecting Enzyme activity:
Temperature

 As the temperature rises, reacting molecules have more and more kinetic energy. This
increases the chances of a successful collision and so the rate increases. Each enzyme is
most active at a specific temperature, called optimum temperature. This optimal
temperature is usually around human body temperature (37.5oC) for the enzymes in
human cells.
 Above this temperature the enzyme denatures since at higher temperatures intra- and
intermolecular bonds are broken as the enzyme molecules gain even more kinetic energy.
Figure 12: Temperature
PH
 pH at which its activity is greatest is called the optimal pH. Extreme pH levels will cause
denaturation. The active site is distorted and the substrate molecules will no longer fit.
Small changes in pH above or below the optimum do not cause a permanent change to
the enzyme, since the bonds can be reformed. H+ and OH- Ions are charged and
therefore interfere with Hydrogen and Ionic bonds that hold together an enzyme, since
they will be attracted or repelled by the charges created by the bonds. This interference
causes a change in shape of the enzyme, and importantly, its active site.

Figure 13: PH
Enzyme Concentration
Rate of enzyme activity is directly proportional to enzyme concentration as long as the substrate
concentration is in excess.
Substrate Concentration
Increasing substrate concentration increases the rate of reaction. This is because more substrate
molecules will be colliding with enzyme molecules, so more product will be formed. After
a certain concentration, any increase will have no effect on the rate of reaction, because
enzymes will effectively become saturated. The enzyme-substrate complex has to dissociate
before the active sites are free to accommodate more substrate.
Inhibitors :
Enzyme inhibitors are substances which alter the catalytic action of the enzyme and
consequently slow down, or in some cases, stop catalysis. Whenever the active site is not
available for binding of the substrate the enzyme activity may be reduced. The chemical
substances which inactivate enzymes are called inhibitors and the process is called enzyme
inhibition. Enzymes catalyze virtually all cellular processes, enzyme inhibitors are among the
most important pharmaceutical agents known. For example, aspirin (acetylsalicylate) inhibits the

enzyme that catalyzes the first step in the synthesis of prostaglandins, compounds involved in
many processes, including some that produce pain.
Three major groups of inhibition:
 Reversible inhibition
 Irreversible inhibition
 Allosteric inhibition
Reversible inhibition.
When the active site or catalytic site is occupied by a substance other than the substrate, its
activity is inhibited. One common type of reversible inhibition is called competitive inhibition.
A competitive inhibitor [I] competes with the substrate for binding the active site of a free
enzyme. While the inhibitor occupies the active site it prevents binding of the substrate to the
enzyme. Many competitive inhibitors are compounds that resemble the substrate and combine
with the enzyme to form an EI complex, but without leading to catalysis. Because the inhibitor
binds reversibly to the enzyme, the inhibition can be overcome by adding more substrate.
Clinical Significance:
 Medical therapy based on competitive inhibition is used to treat patients who have
ingested methanol, a solvent found in gas-line antifreeze. The liver enzyme alcohol
dehydrogenase converts methanol to formaldehyde, which is damaging to many tissues
especially eyes. Ethanol competes effectively with methanol as an alternative substrate
for alcohol dehydrogenase converting it to acetaldehyde. This slows the formation of
formaldehyde, lessening the danger while the kidneys filter out the methanol to be
excreted harmlessly in the urine. Pyrazole is a inhibitor of alcohol dehydrogenase.
 Allopurinol is a drug used to treat gout. Uric acid is formed in the body by oxidation of
hypoxanthine by the enzyme xanthine oxidase. Allopurinol acts as a competitive inhibitor
of xanthine oxidase reducing uric acid formation. Methotrexate is used in cancer therapy.
It‟s a structural analog of folic acid. It inhibits folate reductase and prevents formation of
FH4, which in turn inhibits DNA synthesis.

A noncompetitive inhibitor binds reversibly to both the free enzyme and the ES complex.
 Non-competitive inhibition is observed only for enzymes with two or more substrates.
These inhibitors bring about changes in the 3D structure of the enzyme inactivating.
Compounds that are these types of inhibitors are more useful as drugs since they inhibit
the enzyme independent of the concentration if the substrate. Example; alanine
noncompetitively inhibits the enzyme pyruvate kinase.
Irreversible inhibition
 The irreversible inhibitors are those that bind covalently with or destroy a functional
group on an enzyme . These inhibitors chemically modify and inactivate the enzymes. If
non-competitive inhibitor can be removed only at the loss of enzyme activity, it is known
as irreversible non-competitive inhibition. Examples of non-competitive inhibitor;
iodoacetate inhibiting enzymes like glyceraldehyde 3-phospahte and papin, heavy metals
like silver, mercury, fluoride inhibits emolase.
Clinical Significance
 British anti Lewesite (BAL) is used as antidote for heavy metal poisoning. Heavy
metals inhibit enzymes by reacting with –SH groups. BAL provides –SH for the heavy
metals to act on.
 Antabuse (disulfiram)used in treatment of alcoholism. It inhibits aldehyde
dehydrogenase preventing oxidation of acetaldehyde which accumulates producing
sickening effect leading to aversion to alcohol.
Suicide inhibition is a special type of irreversible non-competitive inhibition in which the
substrate analog is converted to a more effective inhibitor with the help of the enzyme to be
inhibited.

 The new inhibitor formed binds irreversibly with the enzyme. Examples include
allopurinol, 5-fluorouracil. Uncompetitive inhibitor can bind to the ES complex rather
than the free enzyme, binding to an alternative binding site. In contrast to competitive
inhibition, increasing the concentration of substrate will not overcome the effect of the
inhibitor because [I] binds to ES complex and not the free enzyme.
Allosteric inhibition
It is a kind of inhibition when the inhibitor binds to the enzyme at a site other than the active site,
sometimes on a different region in the enzyme called allosteric site. Regulatory enzymes exhibit
increased or decreased catalytic activity in response to certain signals. These enzymes allow the
cell to meet changing needs for energy and for biomolecules required in growth and repair.
Allosteric enzymes function through reversible, non-covalent binding of regulatory compounds
called allosteric modulators or allosteric effectors, which are generally small metabolites or
cofactors. Changes in enzyme-substrate interaction due to the allosteric effects of regulatory
molecules other than the substrate are called heterotropic alloteric modulation. Positive (+)
allosteric effectors increase the enzyme affinity for the substrate. The reverse is true for negative
(-) effectors. Allosteric site at which the positive effector binds is called activator site, negative
effector binds at an inhibitory site.
Feedback regulation is when the product inhibits or activates the enzyme activity in response to
stimuli. If the end product becomes available in the environment, it is unnecessary and wasteful
for the cells to continue to produce the product. Cells have the ability to shut down a pathway
when it is not needed. In biochemical pathways, the product of one reaction becomes the
substrate for the next reaction. When the regulatory enzyme reaction is slowed, all subsequent
enzymes operate at reduced rates as their substrates are depleted. After the product has been
utilized and its concentration decreased, the inhibition is relaxed, and the formation of the
product resumes. Example: Dietary cholesterol restricts the synthesis of cholesterol from acetate
in mammalian tissues.

 Other enzymes are regulated by reversible covalent modification.

 These include the phosphorylation, adenylation, acetylation, uridylation, ADP-
ribosylation, and methylation of enzymes. The covalently attached groups are removed
from the enzyme by separate enzymes. Phosphorylation is the most common type of
regulatory modification found in eukaryotes. It is the addition of phosphate group by
protein kinases to serine, threonine, or tyrosine residues on specific enzymes. An
important example of regulation by phosphorylation is observed in the enzyme glycogen
phosphorylase of muscle and liver.

REFERENCES:
1. Rapoport, S.M. Medical biochemistry. Veb Verlag Volk Gesundh., Berlin 1975.
2. Ding, J. Cell Structure and Function. Part 1 MRCOG Revis. Notes Sample SBAs 2020, 118–119,
doi:10.1017/9781108644396.019.
3. Shahoei, R.; Liu, B.; Chan, K. Case Study : Ribosome Introduction to the ribosome.
4. MAYER, J. The Cell Theory. Nature 1939, 143, 320–321, doi:10.1038/143320a0.
5. Physical, O.; Platform, C. Chapter 3. 아두이노 프로그램의 구조. 25–47.
6. Riley, I.C.D. The Unique and Unusual Properties of Water. 2012, 104, 1–10.
7. USGS Properties of Water--Notes. 2001, 1–4.
8. Mondal, D.S. Chemistry of Carbohydrates; 2017;
9. Norma Gonzalez, Luis Moll, C.A. Chapter 1 股関節概念 Chapter 1 股関節. An Autom. Irrig. Syst.
Using Arduino Microcontroller 2009, 1908, 2–6.
10. Al-Mudhafr, A. Chemistry of fats and oils (Lipids); 2020;
11. Kotb-El-Sayed, M. Basic Enzymology (Part I); 2020;

LECTURE NOTES MCT 201, Shandele G

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MCT 201 Lecture Notes 2022

LEVY MWANAWASA MEDICAL UNIVERSITY

LECTURE NOTES 2022

Biochemistry @ LMMU Page 1

At the end of this course, you should be able to;

Biochemistry @ LMMU Page 2

Biochemistry @ LMMU Page 3

Continuous assessments= 40%

Prescribed and recommended readings:

1. Blanco, A.; Blanco, G. Medical Biochemistry; 2017; ISBN 9780128035870.

2. Echten-deckert, G. Van Biochemistry Metabolic pathways. 2012.

3. Vasudevan, D.; S, S.; Vaidyanathan, K. Textbook of Biochemistry; 2011; ISBN

Biochemistry @ LMMU Page 4

At the end of this unit, you must be able to:

(i) Plasma membrane

Biochemistry @ LMMU Page 5

1. Ribosomes: are sites for protein synthesis.

 Cytosol is a large fluid component of the cytoplasm.

Biochemistry @ LMMU Page 6

Biochemistry @ LMMU Page 7

5. Mitochondria: Cell Powerhouse and site of Cellular Respiration. Makes “ATP”

Biochemistry @ LMMU Page 8

6. ER: Transport and storage of proteins and lipids

7. Golgi bodies: Is the packaging center of the cell

Biochemistry @ LMMU Page 9

 The plasma membrane is composed of a lipid bilayer of phospholipid molecules into

Biochemistry @ LMMU Page 10

Simple Passive Diffusion:

Biochemistry @ LMMU Page 12

Figure 1: Passive transport vs active transport

Facilitated Passive Diffusion:

A characteristic of all living membranes is the formation and maintenance of trans-membrane

Primary Active Transport:

Secondary Active Transport:

Biochemistry @ LMMU Page 13

Further Membrane Transport:

UNIT 2: WATER AND BIOMOLECULES

Biochemistry @ LMMU Page 14

At the end of this unit, you should be able to:

 Define water and mention its properties

Biochemistry @ LMMU Page 15

Biochemistry @ LMMU Page 16

UNIT 3: CHEMISTRY OF CARBOHYDRATES:

At the end of this unit you should be able to:

 Describe the different classes of carbohydrates

Biochemistry @ LMMU Page 17

 monosaccharides, disaccharides, oligosaccharides, and polysaccharides.

 The simplest monosaccharides of biological significance are trioses glyceraldehyde and

Figure 2: The three carbon sugars

The ALDOSE SUGARS!

Biochemistry @ LMMU Page 18

Figure 3: Aldose Sugars

The KETOSE SUGARS!

Biochemistry @ LMMU Page 19

Figure 4: Ketose sugars

Biochemistry @ LMMU Page 20

Figure 5: Chiral Carbon

Figure 6: Enatiomeric forms

Biochemistry @ LMMU Page 21

Figure 7: Epimeric forms

Biochemistry @ LMMU Page 22

Figure 8: Anomeric forms

Thus, a solution of α-D-glucose and a solution of β -D-glucose eventually form identical

Biochemistry @ LMMU Page 23