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BIOCHEMISTRY (BIO-100)
Credit Hrs 4 (3-1)
Course Contents
•
•
Introduction of biochemistry
Biomolecules
– The Molecules and Chemical Reactions
of Life
– Amino Acids and Proteins
– Simple and Complex Carbohydrates
– Lipids and Membranes
– Nucleotides and Nucleic Acids
– Vitamins and Cofactors
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Biochemical Reactions
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Enzymes
Metabolic Pathways
Carbohydrate Metabolism
Lipid Metabolism
Amino Acid Metabolism
Molecular Genetics
DNA and RNA
Translation and the Genetic Code
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LAB WORK
Introduction of biochemistry lab and
biosafety
Units of measurements
Buffer solution preparation
Determination of PH and POH
Numerical problems of PH and POH
Test on carbohydrates
Test on proteins
Test on lipids
Recommended Books
• Fundamentals of Biochemistry: Life at the Molecular Level by Voet,
Donald, Judith G. Voet, and Charlotte W. Pratt.
• Concepts in biochemistry by Rodney Boyer. 3rd Edition.
• Lippincott’s illustrated reviews: Lippincott Williams & Wilkins.
• Biochemistry by Geoffrey Zubay McGraw-Hill.
• Biochemistry by Donald Voet, Judith G. Voet 4, illustrated John
Wiley & Sons.
• Basic concepts in biochemistry: a student’s survival guide by Hiram
F. Gilbert
• Principles of biochemistry by Albert L. Lehninger, David L. Nelson,
Michael M. Cox
• Concepts in biochemistry by Rodney F. Boyer.
Introduction to Carbohydrates
Yasir Waheed
• Carbohydrates are the most abundant organic molecules in
nature.
• They have a wide range of functions, including providing a
significant fraction of the dietary calories for most
organisms, acting as a storage form of energy in the body,
and serving as cell membrane components that mediate
some forms of intercellular communication.
• Carbohydrates also serve as a structural component of
many organisms, including the cell walls of bacteria, the
exoskeleton of many insects, and the fibrous cellulose of
plants.
• The empiric formula for many of the simpler carbo hydrates
is (CH2O)n, hence the name “hydrate of carbon.”
CLASSIFICATION AND STRUCTURE OF
CARBOHYDRATES
• Monosaccharides (simple sugars) can be
classified according to the number of carbon
atoms they contain. Examples of some
monosaccharides commonly found in humans
are listed in Figure 7.1.
Figure 7.1 Examples of monosaccharides found in humans, classified
according to the number of carbons they contain.
• Carbohydrates with an aldehyde as their most
oxidized functional group are called aldoses,
whereas those with a keto as their most
oxidized functional group are called ketoses
(Figure 7.2). For example, glyceraldehyde is an
aldose, whereas dihydroxy acetone is a ketose.
Figure 7.2 Examples of an aldose (A) and a ketose (B) sugar.
• Mono saccharides can be linked by glycosidic bonds
to create larger structures (Figure 7.3).
• Disaccharides contain two mono saccharide units,
oligo saccharides contain from three to about ten
monosaccharide units, whereas polysaccharides
contain more than ten monosaccharide units, and
can be hundreds of sugar units in length.
Figure 7.3 A glycosidic bond between two hexoses producing a disaccharide.
Isomers and epimers
• Compounds that have the same chemical formula but have
different structures are called isomers. For example, fructose,
glucose, mannose, and galactose are all isomers of each other,
having the same chemical formula, C6H12O6.
• Carbohydrate isomers that differ in configuration around only one
specific carbon atom are defined as epimers of each other. For
example, glucose and galactose are C-4 epimers—their structures
differ only in the position of the –OH group at carbon 4. [Note: The
carbons in sugars are numbered beginning at the end that contains
the carbonyl carbon—that is, the aldehyde or keto group (Figure
7.4).] Glucose and mannose are C-2 epimers.
• However, galactose and mannose are NOT epimers—they differ in
the position of –OH groups at two carbons (2 and 4) and are,
therefore, defined only as isomers (see Figure 7.4).
Figure 7.4 C-2 and C-4 epimers
and an isomer of glucose.
Joining of monosaccharides
•
•
•
•
•
Monosaccharides can be joined to form disaccharides, oligosaccharides, and
polysaccharides.
Important disaccharides include lactose (galactose + glucose), sucrose (glucose +
fructose), and maltose (glucose + glucose).
Important polysaccharides include branched glycogen (from animal sources) and
starch (plant sources) and unbranched cellulose (plant sources); each is a polymer
of glucose.
The bonds that link sugars are called glycosidic bonds. These are formed by
enzymes known as glycosyltransferases that use nucleotide sugars such as UDPglucose as substrates.
Glycosidic bonds between sugars are named according to the numbers of the
connected carbons, and with regard to the position of the anomeric hydroxyl
group of the sugar involved in the bond. If this anomeric hydroxyl is in the α
configuration, the linkage is an α-bond. If it is in the β configuration, the linkage is
a β-bond. Lactose, for example, is synthesized by forming a glycosidic bond
between carbon 1 of β-galactose and carbon 4 of glucose. The linkage is,
therefore, a β(1→4) glycosidic bond (see Figure 7.3).
Complex carbohydrates
• Carbohydrates can be attached by glycosidic bonds to
non-carbohydrate structures, including purine and
pyrimidine bases (found in nucleic acids), aromatic
rings (such as those found in steroids and bilirubin),
proteins (found in glycoproteins and proteoglycans),
and lipids (found in glycolipids).
• 1. N- and O-glycosides: If the group on the noncarbohydrate molecule to which the sugar is attached
is an –NH2 group, the structure is an N-glycoside and
the bond is called an N-glycosidic link. If the group is an
–OH, the structure is an O-glycoside, and the bond is
an O-glycosidic link (Figure 7.7).
Figure 7.7 Glycosides: examples of N- and O-glycosidic bonds.
DIGESTION OF DIETARY
CARBOHYDRATES
• The principal sites of dietary carbohydrate digestion are the mouth
and intestinal lumen.
• This digestion is rapid and is catalyzed by enzymes known as
glycoside hydrolases (glycosidases) that hydrolyze glycosidic bonds.
• Because there is little monosaccharide present in diets of mixed
animal and plant origin, the enzymes are primarily
endoglycosidases
that
hydrolyze
polysaccharides
and
oliosaccharides into disaccharidases and hydrolyse tri- and
disaccharides into their reducing sugar components (Figure 7.8).
• Glycosidases are usually specific for the structure and configuration
of the glycosyl residue to be removed, as well as for the type of
bond to be broken. The final products of carbohydrate digestion are
the monosaccharides, glucose, galactose and fructose, which are
absorbed by cells of the small intestine.
Digestion of Disaccharidases
1. Lactase hydrolyses lactose into two molecules, glucose and
galactose:
Lactase
Lactose
Glucose + Galactose
2. Maltase hydrolyses maltose into two molecules of glucose:
Maltase
Maltose
Glucose + Glucose
3. Sucrase hydrolyses sucrose into two molecules of glucose and
fructose:
Sucrase
Sucrose
Glucose + Fructose
15
Figure 7.8 Hydrolysis of a
glycosidic bond.
Figure 7.9 Degradation of
dietary glycogen by salivary or
pancreatic α-amylase.
Figure 4.8a
Figure 4.8b
Figure 4.8c
Figure 4.8d
Absorption of carbohydrates by different
Transporters
21
Abnormal degradation of
disaccharides
• The overall process of carbohydrate digestion
and absorption is so efficient in healthy
individuals that ordinarily all digestible dietary
carbohydrate is absorbed by the time the
ingested material reaches the lower jejunum.
1. Digestive enzyme deficiencies
Genetic deficiencies of the individual
disaccharidases
result
in
disaccharide
intolerance.
Alterations
in
disaccharide
degradation can also be caused by a variety of
intestinal diseases, malnutrition, or drugs that
injure the mucosa of the small intestine.
2. Lactose intolerance: More than three quarters of
the world’s adults are lactose intolerant. The agedependent loss of lactase activity represents a
reduction in the amount of enzyme rather than a
modified inactive enzyme.
It is thought to be caused by small variations in the
DNA sequence of a region on chromosome 2 that
controls expression of the gene for lactase.
Treatment for this disorder is to reduce
consumption of milk.
3. Sucrase-isomaltase complex deficiency: This deficiency results in an
intolerance of ingested sucrose. The disorder is found in about 10% of
the people of Greenland and Canada, whereas 2% of North Americans
are heterozygous for the deficiency.
Treatment includes the dietary restriction of sucrose, and enzyme
replacement therapy.
4. Diagnosis: Identification of a specific enzyme deficiency can be
obtained by performing oral tolerance tests with the individual di saccharides. Measurement of hydrogen gas in the breath is a reliable
test for determining the amount of ingested carbohydrate not
absorbed by the body, but which is metabolized instead by the
intestinal flora (see Figure 7.11).
Figure 7.11 Abnormal lactose metabolism.
MEMBRANE TRANSPORT
Figure 11-1. The relative permeability
of a synthetic lipid bilayer to different
classes of molecules. The smaller the
molecule and, more importantly, the less
strongly it associates with water, the
more rapidly the molecule diffuses
across the bilayer.
There Are Two Main Classes of Membrane Transport Proteins:
Carriers and Channels
•
Carrier proteins (also called carriers, permeases, or transporters)
bind the specific solute to be transported and undergo a series of
conformational changes to transfer the bound solute across the
membrane.
•
Channel proteins, in contrast, interact with the solute to be
transported much more weakly. They form aqueous pores that
extend across the lipid bilayer; when these pores are open, they
allow specific solutes (usually inorganic ions of appropriate size
and charge) to pass through them and thereby cross the
membrane. Transport through channel proteins occurs at a much
faster rate than transport mediated by carrier proteins.
Figure 11-3. Carrier proteins and channel proteins.
(A) A carrier protein alternates between two conformations, so that the
solute-binding site is sequentially accessible on one side of the bilayer
and then on the other. (B) In contrast, a channel protein forms a waterfilled pore across the bilayer through which specific solutes can
diffuse.
Figure 11-4. Passive and active transport compared.
(A) Passive transport down an electrochemical gradient occurs spontaneously,
either by simple diffusion through the lipid bilayer or by facilitated diffusion
through channels and passive carriers. By contrast, active transport requires
an input of metabolic energy and is always mediated by carriers that harvest
metabolic energy to pump the solute against its electrochemical gradient.
Carrier Proteins and Active Membrane Transport
Carrier protein has one or more specific binding sites for its solute (substrate). It
transfers the solute across the lipid bilayer by undergoing reversible
conformational changes that alternately expose the solute-binding site first on
one side of the membrane and then on the other.
1. Coupled carriers couple the uphill transport of one solute across the
membrane to the downhill transport of another.
2. ATP-driven pumps couple uphill transport to the hydrolysis of ATP.
3. Light-driven pumps, which are found mainly in bacterial cells, couple uphill
transport to an input of energy from light, as with bacterio-rhodopsin
Figure 11-8. Three ways of driving active transport.
The actively transported molecule is shown in yellow, and the energy
source is shown in red.
Figure 11-9. Three types of carrier-mediated transport.
This schematic diagram shows carrier proteins functioning as
uniporters, symporters, and antiporters.
One way in which a glucose carrier can be driven by a Na+ gradient. The
carrier oscillates between two alternate states, A and B. In the A state, the
protein is open to the aextracellular space; in the B state, it is open to the
cytosol. Binding of Na+ and glucose is cooperative that is, the binding of either
ligand induces a conformational change that greatly increases the protein's
affinity for the other ligand. Since the Na+ concentration is much higher in the
extracellular space than in the cytosol, glucose is more likely to bind to the
carrier in the A state. Therefore, both Na+ and glucose enter the cell (via an A
to B transition) much more often than they leave it (via B to A transition). The
overall result is the net transport of both Na+ and glucose into the cell.
Because the binding is cooperative, if one of the two solutes is missing, the
other fails to bind to the carrier. Thus, the carrier undergoes a conformational
switch between the two states only if both solutes or neither are bound.
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