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Pharm. Bio-Chem-312-II-A

Fundamentals of Chemistry (University of Karachi)

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Pharmaceutical Chemsitry(BioChemistry)-312-II-A

PHARMACEUTICAL CHEMISTRY-II-A (BIOCHEMISTRY) [Theory]

PHARM 312------------------------------------------------------------------------Cr. Hr. 03
NOTE: The topics will be taught with special reference to their Pharmaceutical Applications.
GENERAL INTRODUCTION AND BASIC BIOCHEMICAL PRINCIPLES:
Role of Pharmaceutical Biochemistry in the health profession. Nature of biochemical
reactions.
BASIC CHEMISTRY OF BIOMOLECULES: (Nature, Classification etc.)
Carbohydrates: Chemistry, Classification, Reactions of Carbohydrates, Optical
activity, Biological and pharmaceutical importance of carbohydrates.
Lipids: Chemistry of Fatty acids and Lipids, Classification (Saponifiable and non-
saponifiable lipids, Simple, Complex and Derived lipids), Reactions of Fatty acids
and other Lipids, Essential fatty acids, Biological and pharmaceutical importance of
lipids.
Proteins and Amino acids: Chemistry, Classification of proteins and amino acids,
Reactions of proteins and amino acids, Organizational levels, Macromolecular
nature of proteins, Biological and pharmaceutical importance of proteins and amino
acids.
Nucleic Acids: Chemistry, Types (DNA, RNA, mRNA, tRNA, rRNA), Purine and
Pyrimidine bases, Nucelosides, Nucelotides, Structures of nucleic acids, Biological
and pharmaceutical importance of nucleic acids.
Vitamins: Chemistry, Classification (Fat-soluble and water-soluble vitamins),
Biological and pharmaceutical importance of vitamins.
Hormones: Chemistry, Classification (Proteinous and nonproteinous hormones,
amino acid derivatives, steroids), Biological and pharmaceutical importance of
hormones.
Enzymes: Chemistry, Classification, Mode of action, Kinetics (Michaelis Menten
Equation and some modifications), Inhibition, Activation, Specificity, Allosteric
enzymes, Factors affecting the rate of an enzyme-catalyzed reaction, Biological
and pharmaceutical importance, Mechanism of action of some important enzymes
(Chymotrypsin, Ribonuclease).
PHARMACEUTICAL CHEMISTRY (BIOCHEMISTRY)
th
Berg JM, Tymoczko JL, Stryer L. Biochemistry. 7 Ed. WH Freeman and
Company; 2010.
Bishop ML, Fody EP, Schoeff LE. Clinical Chemistry: Techniques, Principles and
th
Correlations. 6 Ed. Lippincott Williams & Wilkins; 2009.
th
Champe PC, Harvey RA. Illustrated Biochemistry. 4 Ed. Lippincot Company;
2007.
th
Chaterjee MN. Medical Biochemistry. 7 Ed. Jaypee Brothers Medical Publishers;
2007.
th
Conn EE, Stumpf PK. Outlines of Biochemistry. 5 Ed. John Willey & Sons; 1999.
th
Lehninger AL. Principles of Biochemistry. 4 Ed. CBS Publisher; 2004.
Murray R, Rodwell V, Bender D, Kathleen M, Botham P, Weil A et al. Harper's
th
Illustrated Biochemistry. 28 Ed. Print-Hall; 2009.
West ES, Todd RW, Van BTJ. Text Book of Biochemistry. The MacMillan Co;
1996.
Biochemistry--An Overview
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Biochemistry is the study of the chemical substances found in living organisms and the
chemical interactions of these substances with each other. It deals with the structure and
function of cellular components, such as proteins, carbohydrates, lipids, nucleic acids, and
other biomolecules.
There are different types of biochemical substances like:
Inorganic substances: water and inorganic salts.
Bioorganic substances: Carbohydrates, Lipids, Proteins, and Nucleic Acids.
Complex bioorganic/inorganic Molecules: Enzymes, Vitamins, DNA, RNA, and
Hemoglobin etc.

Carbohydrates: All carbohydrates consist of carbon, hydrogen, and oxygen atoms and are
polyhydroxy aldehydes or ketones or are compounds that can be broken down to form such
compounds. Examples of carbohydrates include starch, fiber, the sweet-tasting compounds
called sugars, and structural materials such as cellulose. The term carbohydrate had its origin
in a misinterpretation of the molecular formulas of many of these substances. For example,
because its formula is C6H12O6, glucose was once thought to be a “carbon hydrate” with the
structure C6·6H2O.
Carbohydrates are carbon compounds that contain large quantities of hydroxyl groups (-OH).
The simplest carbohydrates also contain either an aldehyde moiety (these are termed
polyhydroxyaldehydes) or a ketone moiety (polyhydroxyketones).
All carbohydrates can be classified as either
Monosaccharides
Oligosaccharide(Disaccharides)
Polysaccharides.

The naturally occurring monosaccharides contain three to seven carbon atoms per molecule.
Monosaccharides of specific sizes may be indicated by names composed of a stem denoting
the number of carbon atoms and the suffix -ose. For example, the
terms triose, tetrose, pentose, and hexose signify monosaccharides with, respectively, three,
four, five, and six carbon atoms.
Monosaccharides are also classified as aldoses or ketoses. Those monosaccharides that
contain an aldehyde functional group on the first
carbon atom are called aldoses; those containing
a ketone functional group on the second carbon
atom are ketoses. Combining these classification
systems gives general names that indicate both
the type of carbonyl group and the number of
carbon atoms in a molecule. Thus,
monosaccharides are described as aldotetroses,
aldopentoses, ketopentoses, ketoheptoses, and
so forth. Glucose and fructose are specific
examples of an aldohexose and a ketohexose,
respectively.

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The simplest sugars are the trioses. The possible trioses are shown in part (a) of Figure ;
glyceraldehyde is an aldotriose, while dihydroxyacetone is a ketotriose. Notice that two
structures are shown for glyceraldehyde. These structures are stereoisomers, and hence are
isomers having the same structural formula but differing in the arrangement of atoms or
groups of atoms in
three-dimensional
space. If you make
models of the two
stereoisomers of
glyceraldehyde,
you will find that
you cannot place
one model on top
of the other and
have each functional group
point in the same direction.
However, if you place one of
the models in front of a mirror,
the image in the mirror will be
identical to the second
stereoisomer in part (b) of
Figure
Molecules that are nonsuperimposable (nonidentical) mirror images of each other are a type
of stereoisomer called enantiomers (Greek enantios, meaning “opposite”).
A key characteristic of enantiomers is that they have a carbon atom to which four different
groups are attached. Note, for example, the four different groups attached to the central
carbon atom of glyceraldehyde (part (a) of Figure ). A carbon atom that has four different
groups attached is a chiral carbon. If a molecule contains one or more chiral carbons, it is
likely to exist as two or more stereoisomers. Dihydroxyacetone does not contain a chiral
carbon and thus does not exist as a pair of stereoisomers. Glyceraldehyde, however, has a
chiral carbon and exists as a pair of enantiomers. Except for the direction in which each
enantiomer rotates plane-polarized light, these two molecules have identical physical
properties.
The two enantiomers of glyceraldehyde are especially important because monosaccharides
with more than three carbon atoms can be considered as being derived from them. Thus, D-
and L-glyceraldehyde provide reference points for designating and drawing all other
monosaccharides. Sugars whose Fischer projections terminate in the same configuration as
D-glyceraldehyde are designated as D sugars; those derived from L-glyceraldehyde are
designated as L sugars.
By convention, the penultimate (next-to-last) carbon atom has been chosen as the
carbon atom that determines if a sugar is D or L. It is the chiral carbon farthest
from the aldehyde or ketone functional group.

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Although a variety of monosaccharides are found in living organisms, three hexoses are
particularly abundant: D-glucose, D-galactose, and D-fructose (Figure). Glucose and
galactose are both aldohexoses, while fructose is a ketohexose.

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Previously, you learned that monosaccharides can form cyclic structures by the reaction of the
carbonyl group with an OH group.

Disaccharides (C12H22O11) are sugars composed of two monosaccharide units that are joined
by a carbon–oxygen-carbon linkage known as a Glycosidic Linkage. This linkage is
formed from the reaction of the anomeric carbon of one cyclic monosaccharide with the OH
group of a second monosaccharide.

The disaccharides differ from one another in their monosaccharide constituents and in the
specific type of glycosidic linkage connecting them. There are three common disaccharides:
Maltose, Lactose, and Sucrose. All three are white crystalline solids at room temperature
and are soluble in water. We’ll consider each sugar in more detail.

MALTOSE
Maltose occurs to a limited extent in sprouting grain. It is formed most often by the partial
hydrolysis of starch and glycogen. In the manufacture of beer, maltose is liberated by the
action of malt (germinating barley) on starch; for this reason, it is often referred to as malt
sugar. Maltose is about 30% as sweet as sucrose. The human body is unable to metabolize
maltose or any other disaccharide directly from the diet because the molecules are too large
to pass through the cell membranes of the intestinal wall.
Therefore, an ingested disaccharide must first be broken down by hydrolysis into its two
constituent monosaccharide units.
In the body, such hydrolysis reactions are catalyzed by enzymes such as Maltase. The same
reactions can be carried out in the laboratory with dilute acid as a catalyst, although in that
case the rate is much slower, and high temperatures are required. Whether it occurs in the
body or a glass beaker, the hydrolysis of maltose produces two molecules of D-glucose.

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LACTOSE
Lactose is known as milk sugar because it occurs in the milk of humans, cows, and other
mammals. In fact, the natural synthesis of lactose occurs only in mammary tissue, whereas
most other carbohydrates are plant products. Human milk contains about 7.5% lactose, and
cow’s milk contains about 4.5%. This sugar is one of the lowest ranking in terms of sweetness,
being about one-sixth as sweet as sucrose. Lactose is produced commercially from whey, a
by-product in the manufacture of cheese. It is important as an infant food and in the
production of penicillin.

Lactose is a reducing sugar composed of one molecule of D-galactose and one molecule of
D-glucose joined by a β-1,4- glycosidic bond (the bond from the anomeric carbon of the first
monosaccharide unit being directed upward). The two monosaccharides are obtained from
lactose by acid hydrolysis or the catalytic action of the enzyme Lactase:

Many adults and some children suffer from a deficiency of lactase. These individuals are said
to be lactose intolerant because they cannot digest the lactose found in milk. A more serious
problem is the genetic disease galactosemia, which results from the absence of an enzyme
needed to convert galactose to glucose. Certain bacteria can metabolize lactose, forming
lactic acid as one of the products. This reaction is responsible for the “souring” of milk.

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SUCROSE
Sucrose, probably the largest-selling pure organic compound in the world, is known as beet
sugar, cane sugar, table sugar, or simply sugar. Most of the sucrose sold commercially is
obtained from sugar cane and sugar beets (whose juices are 14%–20% sucrose) by
evaporation of the water and recrystallization. The dark brown liquid that remains after the
recrystallization of sugar is sold as molasses.
The sucrose molecule is unique among the common disaccharides in having an α-1,β-2
glycosidic (head-to-head) linkage. Because this glycosidic linkage is formed by the OH group
on the anomeric carbon of α-D-glucose and the OH group on the anomeric carbon of β-D-
fructose, it ties up the anomeric carbons of both glucose and fructose.

This linkage gives sucrose certain properties that are quite different from those of maltose and
lactose. As long as the sucrose molecule remains intact, neither monosaccharide “uncyclizes”
to form an open-chain structure. Thus, sucrose is incapable of mutarotation and exists in only
one form both in the solid state and in solution. In addition, sucrose does not undergo
reactions that are typical of aldehydes and ketones. Therefore, sucrose is a nonreducing
sugar.

The hydrolysis of sucrose in dilute acid or through the action of the enzyme Sucrase (also
known as Invertase) gives an equimolar mixture of glucose and fructose. This 1:1 mixture is
referred to as invert sugar because it rotates plane-polarized light in the opposite direction
than sucrose.
The hydrolysis reaction has several practical applications. Sucrose readily recrystallizes from
a solution, but invert sugar has a much greater tendency to remain in solution. In the
manufacture of jelly and candy and in the canning of fruit, the recrystallization of sugar is
undesirable. Therefore, conditions leading to the hydrolysis of sucrose are employed in these
processes. Moreover, because fructose is sweeter than sucrose, the hydrolysis adds to the
sweetening effect. Bees carry out this reaction when they make honey.

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The Polysaccharides are the most abundant carbohydrates in nature and serve a variety of
functions, such as energy storage or as components of plant cell walls. Polysaccharides are
very large polymers composed of tens to thousands of monosaccharides joined together by
glycosidic linkages. The three most abundant polysaccharides are Starch, Glycogen, and
Cellulose. These three are referred to as Homopolymers because each yields only one type
of monosaccharide (glucose) after complete hydrolysis. Heteropolymers may contain sugar
acids, amino sugars, or noncarbohydrate substances in addition to monosaccharides.
Heteropolymers are common in nature (gums, pectins, and other substances).

STARCH
Starch is the most important source of carbohydrates in the human diet and accounts for more
than 50% of our carbohydrate intake. It occurs in plants in the form of granules, and these are
particularly abundant in seeds (especially the cereal grains), where they serve as a storage
form of carbohydrates. We often think of potatoes as a “starchy” food, yet other plants contain
a much greater percentage of starch (potatoes 15%, wheat 55%, corn 65%, and rice 75%).
Commercial starch is a white powder.
Starch is a mixture of two polymers: Amylose and Amylopectin. Natural starches consist of
about 10%–30% amylose and 70%–90% amylopectin. Amylose is a linear polysaccharide
composed entirely of D-glucose units joined by the α-1,4- glycosidic linkages we saw in
maltose. Experimental evidence indicates that amylose is not a straight chain of glucose units
but instead is coiled like a spring, with six glucose monomers per turn. When coiled in this
fashion, amylose has just enough room in its core to accommodate an iodine molecule. The
characteristic blue-violet color that appears when starch is treated with iodine is due to the
formation of the amylose-iodine complex. This color test is sensitive enough to detect even
minute amounts of starch in solution.

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Dextrins are glucose polysaccharides of intermediate size. The shine and stiffness imparted to
clothing by starch are due to the presence of dextrins formed when clothing is ironed.
Because of their characteristic stickiness with wetting, dextrins are used as adhesives on
stamps, envelopes, and labels; as binders to hold pills and tablets together; and as pastes.
Dextrins are more easily digested than starch and are therefore used extensively in the
commercial preparation of infant foods.
The complete hydrolysis of starch yields, in successive stages, glucose:
Starch → Dextrins → Maltose → Glucose
In the human body, several enzymes known collectively as amylases degrade starch
sequentially into usable glucose units.

GLYCOGEN
Glycogen is the energy reserve carbohydrate of animals. Practically all mammalian cells
contain some stored carbohydrates in the form of glycogen, but it is especially abundant in the
liver (4%–8% by weight of tissue) and in skeletal muscle cells (0.5%–1.0%). Like starch in
plants, glycogen is found as granules in liver and muscle cells. When fasting, animals draw on
these glycogen reserves during the first day without food to obtain the glucose needed to
maintain metabolic balance.
Glycogen is structurally quite similar to amylopectin, although glycogen is more highly
branched (8–12 glucose units between branches) and the branches are shorter. When treated
with iodine, glycogen gives a reddish brown color. Glycogen can be broken down into its D-
glucose subunits by acid hydrolysis or by the same enzymes that catalyze the breakdown of
starch. In animals, the enzyme Phosphorylase catalyzes the breakdown of glycogen to
phosphate esters of glucose.

About 70% of the total glycogen in the body is stored in muscle cells. Although the percentage
of glycogen (by weight) is higher in the liver, the much greater mass of skeletal muscle stores
a greater total amount of glycogen.

CELLULOSE
Cellulose, a fibrous carbohydrate found in all plants, is the structural component of plant cell
walls. Because the earth is covered with vegetation, cellulose is the most abundant of all
carbohydrates, accounting for over 50% of all the carbon found in the vegetable kingdom.
Cotton fibrils and filter paper are almost entirely cellulose (about 95%), wood is about 50%
cellulose, and the dry weight of leaves is about 10%–20% cellulose. The largest use of
cellulose is in the manufacture of paper and paper products. Although the use of noncellulose
synthetic fibers is increasing, rayon (made from cellulose) and cotton still account for over
70% of textile production. Like amylose, cellulose is a linear polymer of glucose. It differs,
however, in that the glucose units are joined by β-1,4- glycosidic linkages, producing a more
extended structure than amylose (part (a) of Figure). This extreme linearity allows a great deal
of hydrogen bonding between OH groups on adjacent chains, causing them to pack closely
into fibers (part (b) of Figure). As a result, cellulose exhibits little interaction with water or any
other solvent. Cotton and wood, for example, are completely insoluble in water and have
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considerable mechanical strength. Because cellulose does not have a helical structure, it does
not bind to iodine to form a colored product.

Cellulose yields D-glucose after complete acid hydrolysis, yet humans are unable to
metabolize cellulose as a source of glucose. Our digestive juices lack enzymes that can
hydrolyze the β-glycosidic linkages found in cellulose, so although we can eat potatoes, we
cannot eat grass. However, certain microorganisms can digest cellulose because they make
the enzyme Cellulase, which catalyzes the hydrolysis of cellulose. The presence of these
microorganisms in the digestive tracts of herbivorous animals (such as cows, horses, and
sheep) allows these animals to degrade the cellulose from plant material into glucose for
energy.

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