THE UNIVERSITY OF ZAMBIA

SCHOOL OF MEDICINE

DEPARTMENT OF PHYSIOLOGICAL SCIENCES

Telephone: 252641 P.O. Box 50110
211440 (UTH) 254824 (Pre-Clinical) Ridgeway Campus Lusaka, Zambia.
Fax: + 260 – 1 – 250753

Bachelor of Science in Nursing

BIOCHEMISTRY BCN 215

MODULE 1 (General Biochemistry I)

(Water, amino acids and peptides, and carbohydrates)
Gibson Sijumbila

BSc (Human Biology) University of Zambia

MB ChB, University of Zambia

MD, University of Dundee, UK

First Edition - 2011

1
Table of contents

Page number
Introduction to module 1……………………………………………………………………….. 3
Aim…………………………………………………………………………………………. 3
Objectives…………………………………………………………………………………….. 3
Study skills…………………………………………………………………………………… 3
Need help…………………………………………………………………………………….. 4
Time frame…………………………………………………………………………………… 4
Structure of module………………………………………………………………………….. 4
Assessment ………………………………………………………………………………….. 4
Prescribed Readings…………………………………………………………………………. 4
Recommended Readings……………………………………………………………………... 4
Unit 1 Water……………………………………………………………….................................. 5
Introduction…………………………………………………………………………………… 5
Aim ………………………………………………………………………………………….. 5
Objectives…………………………………………………………………………………….. 5
Equipment …………………………………………………………………………………… 5
Other resources………………………………………………………………………………. 5
Content……………………………………………………………………………………….. 5
Properties of water………………………………………………………………………………. 5
Buffers…………………………………………………………………………………………….. 9
The phosphate buffer……………………………………………………………………………. 9
Bicarbonate buffer………………………………………………………………………………. 9
Questions…………………………………………………………………………………………. 11
Unit 2 Amino acids and peptides……………………………………………………………… 12
Introduction…………………………………………………………………………………… 12
Aim ………………………………………………………………………………………….. 12
Objectives…………………………………………………………………………………….. 12
Equipment …………………………………………………………………………………… 12
Other resources………………………………………………………………………………. 12
Content……………………………………………………………………………………….. 12
Amino acid structure…………………………………………………………………………… 13
Properties of amino acids……………………………………………………………………… 14
Properties of amino acids as determined by their R groups………………………………. 17
Amino acid function……………………………………………………………………………... 18
Some peptides with biologically important effects………………………………………….. 19
Questions…………………………………………………………………………………………. 19
Unit 3 Carbohydrates………………………………………………………………………….. 20
Introduction…………………………………………………………………………………… 20
Aim ………………………………………………………………………………………….. 20
Objectives…………………………………………………………………………………….. 20
Equipment …………………………………………………………………………………… 20
Other resources………………………………………………………………………………. 20
Content……………………………………………………………………………………….. 21
Classification…………………………………………………………………………………….. 21
Glycogen …………………………………………………………………………………………. 22
Starch……………………………………………………………………………………………… 23
Peptidoglycans…………………………………………………………………………………… 23
Glycosaminoglycans……………………………………………………………………………. 24
Glycoconjugates (proteoglycans, glycoproteins, glycolipids)…………………………….. 25
Questions…………………………………………………………………………………………. 26
Summary of the module……………………………………………………. 27

2
 MODULE 1

Introduction.
The best way for you to learn and understand this course is to start with general biochemistry
followed by metabolism. This module covers topics on water, amino acids and peptides and
carbohydrates. I would like to stress one point before you proceed with your reading; we
don’t expect you to memorize various chemical structures as it is unnecessary in this course.
We however expect you to remember certain structural features of biomolecules that
determine their properties. For instance we know that carbohydrates are more soluble in water
than lipids because carbohydrates have polar hydroxyl groups which interact favorably with
water where as lipids don’t have polar groups. As you can see from the above example you
can easily offer an explanation without having memorized the structures of carbohydrates and
lipids. Functions of biomolecules will be discussed in broad terms to cover the most important
aspects. At the end of each unit you will find questions that will test your understanding of the
subject. Please make an effort to answer these questions.

Aim
The aim of this module is to introduce you to the principles of general biochemistry.

Objectives
By the end of the module you should be able to:
1. Describe properties of water.
2. Discuss the structural features and properties of water, amino acids and peptides, and
carbohydrates.
3. Outline various functions of amino acids, peptides and carbohydrates.

Study skills
The notes that you will find under the core text are comprehensive enough for you to pass
your exams. However I would strongly urge you to read the prescribed and recommended text
books as well so that you can broaden your understanding of the subject. Certain websites
have very good information on various topics in biochemistry; so whenever possible, please
check on various websites shown in respective units under ´Other Resources´. Some
molecular structures have been included for reference purposes. You are not supposed to
memorize molecular structures as that would be beyond the scope of the course.

3
 Need help?
In case you have difficulties during the course please get in touch with the Director, Institute
of Distance Education, or the resident lecturer in your province.

Time frame
You will be expected to spend at least 60 hours of study time on this module.

Structure of the module

You will find that the module is divided into three units. Units I, 2, and 3 cover the topics of
water, amino acids and peptides, and carbohydrates respectively. Each unit has a core text on
the topic and an exercise at the end. You are required to read the text and attempt the exercise
at the end before proceeding to the next unit. If you find it difficult to answer the questions
first time do not be discouraged; all beginners have problems in the initial stages. But as time
goes on you will begin to understand the subject matter and be able to answer the questions.

Assessments
Continuous assessment 40%
Assignments 10%
Tests 30%
Final 60

Prescribed Readings:

1. Reginald H. Garrett and Charles M. Grisham (2007). Biochemistry, Third Edition

ISBN-13: 978-0-497-11912-8
2. Michael M. Cox and David L. Nelson (2008). Lehninger Principles of Biochemistry, Fifth
Edition. ISBN:978-0-230-22699-9

Recommended Readings:

1. Jeremy M. Berg, John L. Tymoczko and Lubert Stryer (2006) Biochemistry, Sixth
Edition. ISBN-13: 978-0-7167 – 8724 – 2.
2. John W. Baynes, Marek H. Dominiczak (2008), Medical Biochemistry, Second Edition.
ISBN 978 0 7234 3341 5
3. Jeannette Naish, Patricia Revest and Denise S. Court (2009), Medical Sciences, First
Edition. ISBN: 978 0 702 026 799
4. MN Chatterjea and Rana Shinde (2008), Medical Biochemistry, Seventh Edition. ISBN
81 – 8448 – 134 – 9
5. Barth, G Butler, P Hammond. Biochemical investigations in laboratory medicine. 2001,
ACB Venture pubs. ISBN 0-902-42934-5.

4
 UNIT 1
WATER

1.1 Introduction
Water is the most abundant compound on earth's surface, covering about 70% of the surface.
A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds.
Water exists in different states depending upon ambient conditions; it is a liquid at room
temperature, but under freezing conditions it turns into solid ice. Because of its
electrochemical properties water is an ideal solvent for many biomolecules and it helps
determine their three dimensional structures.

1.2 Aim
The aim of the unit is to introduce you to the basic chemistry and properties of water.

1.3 Objectives
By the end of this unit you should be able to:
1. Explain the properties of water.
2. Explain the importance of buffers in biological systems.
3. Describe the interaction between water and other molecules.

1.4 Equipment needed

None

1.5 Other resources

a) http://www.biochem.arizona.edu/classes/bioc462/462a/lectures/08/lecture_2_water.pd
f
b) http://www.varsitynotes.com/biochemistry/medical_biochemistry.html
c) http://medicalppt.blogspot.com/search/label/biochemistry

1.6 Content
Properties of water
Have you ever wondered why all living organisms need water for their survival? Water has
several properties that make it an ideal solvent in all organisms. One of the properties is that
water molecules carry partial charges on their surface rendering them polar molecules.
By chemical definition polarity refers to a concept which describes how equally bonding
electrons are shared between atoms. There are covalent bonds (electron pair is shared)
between oxygen and hydrogen atoms of water with a bond angle of 104.5o (Fig. 1.1).

5
 Fig. 1.1 Structure of a water molecule showing partial charges on oxygen
and hydrogen atoms

This sharing of electrons between oxygen and hydrogen is unequal as electrons tend to spend
more time on the side of oxygen than hydrogen and this result in a polar covalent bond where
the oxygen atom ends up with partial negative charge and each hydrogen atom with partial
positive charge. The second important property of water is its ability to form weak bonds with
other water molecules or other polar molecules. How does this come about? Because of the
partial charges on each water molecule weak attractive forces develop between opposite
partial charges; the partial positive charge on one water molecule attracts a partial negative
charge of another which is also weakly bonded to another molecule with opposite charge.
These weak attractions are referred to as hydrogen bonds.

Hydrogen bond

Fig. 1.2 Structure of a water molecule

showing partial charges on oxygen and
hydrogen atoms and a hydrogen bond.

The length of the bond is about twice that of a covalent bond. Each water molecule can form
hydrogen bonds with four other water molecules (Fig. 1.2 and Fig. 1.3).

6
 Fig. 1.3

A water molecule hydrogen bonded with four other water molecules

Hydrogen bonds are weaker than covalent bonds (about 25 x weaker). These hydrogen bonds
give water ideal properties for supporting organisms. Because of hydrogen bonds water has a
high melting point because these weak bonds need to be disrupted before the crystalline state
can be melted to liquid water. A large amount of heat is required to raise the temperature of 1
gm of water 1oC due to the fact that hydrogen bonds must be broken to increase the kinetic
energy (motion of molecules) and temperature of a substance. Water also requires a large
amount of heat to evaporate because hydrogen bonds must be broken to change water from
liquid to gaseous state. The polarity on water molecules means that water can interact with
and dissolve other polar compounds and those that ionize (electrolytes) because they are
hydrophilic. Water molecules do so by aligning themselves around the electrolytes to form
solvation spheres which are shells of water molecules around each ion (Fig. 1.4).

Fig. 1.4 A salvation sphere. Barium ion

is surrounded by water molecules

7
Solubility of organic molecules in water depends on polarity and the ability to form hydrogen
bonds with water. As the number of polar groups increases in a molecule, so does its
solubility in water.
Nonpolar molecules are not soluble in water because water molecules interact with each other
rather than with nonpolar molecules. These molecules tend to be excluded from water and
associate with each other; this association is referred to as hydrophobic interaction.
Molecules such as detergents or surfactants are amphipathic (have both hydrophilic and
hydrophobic portions).These molecules usually have a hydrophobic chain of 12 carbon atoms
plus an ionic or polar end. Soaps are alkali metal salts of long chain fatty acids
e.g. sodium palmitate
e.g. sodium dodecyl sulfate (synthetic detergent)
In solution they all form micelles which are spheres in which hydrophilic heads are hydrated
and face outside and hydrophobic tails face inward. Soaps are good detergents because they
help in removal of grease and oils by trapping them inside.

There are four major noncovalent forces involved in the structure and function of
biomolecules. Hydrogen bonds as discussed above play a significant role in defining the
properties of water and occur between and within molecules thereby stabilizing the three
dimensional structure of nucleic acids and proteins. The hydrophobic interactions are
important in protein shape and membrane structure. In situation where there are two
oppositely charged ends electrostatic interactions (ionic bonds) occur and the van der Waals
forces which occur between neutral atoms can be attractive or repulsive,depending upon the
distance between the two atoms (Lehninger 2008: Page 45).

Ionization of water
Pure water has another unique feature. It has the capacity to ionize to a very slight extent.
Therefore water can act as a proton donor (acid) or proton acceptor (base).
+ - + -
2H2O -à H3O + OH , but usually written as H2O -à H + OH
Equilibrium constant for water:
+ - -16 o
Keq = [H ][OH ] = 1.8 x 10 M at 25 C

[H2O]

if [H20] is 55.5 M à 1 liter of H2O is 1000 g

1 mole of H2O is 18 g

Can rearrange equation to the following:

-16
1.8 x 10 M(55.5 M) = [H+][OH-]
-14 2
1.0 x 10 M = [H+][OH-]

At equilibrium, [H+] = [OH-], so

-14 2 2
1.0 x 10 M = [H+]

8
 -7 +
1.0 x 10 = [H ]

(Lehninger 2008: Page 55)

pH scale

pH = - log [H+], so at equilibrium

-7
pH = -log (1.0 x 10 )
= 7
pH <7 is acidic, pH > 7 is basic or alkaline
+
1 change in pH units equals a 10-fold change in [H ]
Do not despair if you cant understand the above calculations; the most important point for
you to remember is that a neutral solution has hydrogen ion concentration of 1.0 X 10-7 or pH7
and an acid solution has a pH less than 7 while an alkaline solution has a pH greater than 7.
Because of its polar nature ability to ionize to a limited extent water forms an ideal solvent
for buffer systems.

Buffers are aqueous systems that tend to resist changes in pH when small amounts of acid
(H+) or base (OH-) are added. A buffer system consists of a weak acid and its conjugate base
(more common) or a weak base and its conjugate acid (less common). Buffers are very
important in organisms for several reasons. Most enzymes that catalyze biochemical
reactions are very sensitive to slight changes in pH and any extreme changes in pH can impair
their function. The intracellular and extracellular fluids of multicellular organisms therefore
need to be near constant pH and these body fluids must be protected against changes in pH all
the time as acids and bases are continuously being produced by metabolic processes.
Biological buffers include HCO3–, phosphate and proteins which accept or release protons to
resist a change in pH.

The phosphate buffer system

Acts in the cytoplasm of all cells and consists of dihydrogen phosphate (H2PO4- ) as a proton
donor and hydrogen phosphate (HPO42-) as a proton acceptor.

The bicarbonate buffer system

Blood plasma is in part buffered by the bicarbonate system consisting of carbonic acid
(H2CO3) as proton donor and bicarbonate (HCO3-) as proton acceptor
H2CO3 H+ + HCO3-

The buffer system is more complex than other conjugate acid-base pairs because one of the
components, carbonic acid is formed from dissolved (d) CO2 and water in a reversible
reaction

CO2(d) + H2O H2CO3

9
Dissolved CO2 is in equilibrium with CO2 of the gas phase

[ H 2CO3 ]
K2 =
[CO2 (d )][ H 2O]
CO2(g) CO2(d)
[CO2 (d )]
K3 =
[CO2 ( g )]
The pH of a bicarbonate buffer system depends on the concentration of H2CO3 and HCO3–,
the proton donor and acceptor respectively. The concentration of H2CO3 depends on the
concentration of dissolved CO2, which in turn depends on the concentration of CO2 in the gas
phase (partial pressure of CO2).
Human blood plasma normally has a pH of about 7.4. In uncontrolled diabetes for example
there is acidosis and pH can fall to dangerously lower levels resulting in cell damage or death
Similarly other conditions can increase pH to lethal levels

If you breathe more deeply and eliminate more CO2, you can drop the levels of carbonic acid
and counteract an influx of acid in the body (metabolic acidosis) by shifting the equilibrium
away from the H+ (compensatory respiratory alkalosis)Lehninger (2008: 62).
In an opposite way, if the blood pH rises (metabolic alkalosis), by breathing more shallowly,
CO2 is retained and the blood pH decreases (H+ increases) (compensatory respiratory

10
acidosis).

Perhaps at this point it may be worthwhile to look at the causes of disturbances in acid-base
balance in our bodies. Respiratory acidosis is caused by alveolar hypoventilation and
accumulation of CO2 in body as seen in airway obstruction, neuromuscular disorders, diseases
of the central nervous system or in chronic obstructive lung diseases like emphysema.
Respiratory alkalosis is caused by decreased alveolar pressure of CO2 and is most commonly
found in hyperventilation due to anxiety. This can also be caused by salicylate poisoning,
fever, artificial ventilation, and high altitude (since there is a decrease in total atmospheric
pressure and therefore alveolar PCO2 ). Metabolic acidosis caused by disorders in which
excess lactic acid, acetoacetic acid or β-hydroxy/
butyric acid are produced, or ingestion of salicylates, ethylene glycol, or methyl alcohol all of
which produce strong organic acids.
Metabolic alkalosis is caused by intake of excess alkali (sodium bicarbonate) or abnormal loss
of acid (prolonged vomiting).

Please attempt the following questions before you proceed any further.
1. Explain what gives water its unique physical features.
2. Describe the weak non-covalent bonds that play a major role in structure and function
of macromolecules.
3. What is pH? Explain how the value of pH changes with acidity of the solution.
4. Explain why water dissolves polar but not non polar substances.
5. What are biological buffers? Explain the importance of buffers in biological systems.
6. Describe the terms hydrophobic and hydrophilic.
7. Describe the bicarbonate buffer and explain how the bicarbonate buffer responds to
pH changes in plasma.

11
 UNIT 2
AMINO ACIDS AND PEPTIDES

2.1 Introduction
Amino acids are very important precursors of versatile molecules like peptides and proteins
which have diverse functions in the body. Knowledge of the properties of amino acids is vital
in understanding the three-dimensional structures of proteins and their function.

2.2 Aim
The aim of the unit is to introduce to you general properties and reactions of amino acids.

2.3 Objectives
By the end of the unit you should be able to:
1. Classify amino acids according to side chain properties
2. Explain the chemical properties of amino acids
3. Explain what a peptide bond is.
4. List examples of biologically important peptides

2.4 Equipment
None

2.5 Other resources

a) http://mcb.berkeley.edu/courses/mcb102/handouts/Doudna/Lecture2.pdf
b) http://www.escience.ws/b572/L9/L9.htm
c) http://www.sp.uconn.edu/~bi107vc/fa02/terry/proteins.html
d) http://www.biochem.arizona.edu/classes/bioc462/462a/NOTES/Amino_Acids/amino_
acids.htm

2.6 Content
In nature there are over 300 amino acids but only 20 are found in human protein. Each amino
acid has at least one amino and one acidic functional group as the name implies. The different
properties of amino acids result from variations in the structures of amino acid side chains ( R
groups). Each amino acids has a special common name; however a three letter abbreviation
for the name is used most of the time. A single letter abbreviation is used in long protein
structures (Table 1) (Harper 2003: 14). These properties crucial to the structure and function
of peptides and proteins include:
o Stereochemistry which involves the relative spatial arrangement of atoms.
within molecules
o Relative polarity which is how equally bonding electrons are shared between
atoms and this determines the extent of interaction with water.
o Hydrogen bonding properties.

12
 o Ionization properties.
o Other chemical properties.

Amino acid structure.

The amino acid has an –α-carbon to which are linked a hydrogen, distinctive side chain (R
group), a carboxyl group and an amino group (Fig. 2.1).

An α- amino acid consists of - an amino group This carbon

- a carboxyl group atom is
- a hydrogen atom
called α-
- a distinctive R group
(side chain) carbon
because its
Fig. 2.1 adjacent to
the
carboxyl
(acidic)
Both the α-amino group (amino group substituent on the α-carbon) and the α-carboxyl group group
(carboxyl substituent on the α-carbon) are ionizable as shown above. When both are ionized
the net charge of an amino acid is zero; this form of an amino acid is referred to as the
zwitterion and amino acids exist as zwitterions at physiological pH.
The stereochemistry of amino acids deserves some attention for the reason below. When you
look at the α-carbon above you will see that it is asymmetric because it is linked to four
different substituents, and this is true of all amino acids except for glycine, for which the R
group is a hydrogen atom. Because of this asymmetry amino acids can exist as either L- or D-
isomers. In proteins only the L-amino acids are found. Even though naturally occurring D-
amino acids are there, they are never found in protein. At your level you are
not expected to know the one letter or three letter abbreviations and the table below the
(Table 2.1)is given just for reference purposes.
Amino Acid Abbreviations
amino acid (or residue 3-letter 1-letter Mnemonic for 1-letter
in protein) abbreviation abbreviation abbreviation
Glycine Gly G Glycine
Alanine Ala A Alanine
Valine Val V Valine
Leucine Leu L Leucine
Isoleucine Ile I Isoleucine
Proline Pro P Proline
Methionine Met M Methionine

13
 Phenylalanine Phe F Fenylalanine
tWyptophan (or tWo
Tryptophan Trp W
rings)
Tyrosine Tyr Y tYrosine
Serine Ser S Serine
Threonine Thr T Threonine
Cysteine Cys C Cysteine
Aspartic Acid Asp** D asparDic acid
Glutamic Acid Glu* E gluEtamic acid
Asparagine Asn** N asparagiNe
Glutamine Gln* Q Q-tamine
Histidine His H Histidine
Lysine Lys K (before L)
Arginine Arg R aRginine
Table 2.1
Properties of amino acids
In you look closely at the general structure of an amino acid given above you will realize that
all amino acids have a hydrogen, an amino group and a carboxyl group linked to the α-carbon
and the only part that distinguishes them is the R-group. The R-group is what determines
properties of amino acids (Table 2.2). There is a wide diversity in the chemical properties of
amino acid side chains, but they can be grouped into classes, sometimes with overlapping
"membership" (e.g., tyrosine is both aromatic and hydroxyl-containing).
Side Chain Class Amino Acids
glycine, alanine, valine, leucine,
Aliphatic
isoleucine
Cyclic proline
Aromatic phenylalanine, tyrosine, tryptophan
Hydroxyl-containing serine, threonine, tyrosine
Sulfur-containing cysteine, methionine
Basic histidine, lysine, arginine
aspartic acid, glutamic acid, asparagine,
Acidic and their amides
glutamine

Table 2.2

Nonpolar, aliphatic R groups (Fig. 2.2)

The amino acids in this group are glycine, alanine, valine, leucine, isoleucine, proline and
methionine. These amino acids have a hydrophobic hydrocarbon chain (shown below as

14
shaded parts of amino acids). In a way glycine is an exception because it has some degree of
water solubility. Perhaps one or two points are worth mentioning in this group at this stage. If
you look at the structure of proline you will notice that it has a rigid ring structure and this is
of importance in protein structure as will be explained later and methionine has a sulfur atom
with a terminal methyl group. Methionine´s terminal methyl group is important in
metabolism.

Fig. 2.2
Aromatic R groups (Fig. 2.3)
The amino acids in this group are phenylalanine, tryptophan and tyrosine The side chains of
these amino acids have aromatic rings with conjugated double bonds (shown below as shaded
parts of amino acids). They are generally hydrophobic to various degrees with tyrosine being
the least hydrophobic because it has an -OH group

Polar, uncharged R groups (Fig. 2.4)

15
Polar uncharged R group
Amino acids in this group are serine, threonine, asparagine, glutamine and cysteine. These
amino acids have polar side chains meaning there is unequal sharing of electrons in some of
the covalent bonds of the side chains resulting in partial charges (shown below as shaded parts
of amino acids). It is important to remember that the side chains of these amino acids are not
ionizable and hence are not charged. The only exception is cysteine which may be ionizable
under certain conditions. It is also important to realize that cysteine has a sulfur atom in its
structure.

Fig. 2.4

Positively charged R groups (sometimes called "basic" R groups) (Fig. 2.5)

Amino acids in this group are arginine, lysine and histidine. The side chains of these amino
acids are ionizable and at physiological pH they are positively charged (shown below as
shaded parts of amino acids).

Fig. 2.5

16
 Negatively charged R groups (sometimes called "acidic" R groups) (Fig. 2.6)
Amino acids in this group are aspartate and glutamate with ionizable side chains (shown
below as shaded parts of amino acids). These amino acids are negatively charged at
physiological pH.

(Lehninger 2008: 72) Fig. 2.6

Properties of amino acids as determined by R groups

Armed with the general properties of the amino acids lets look at how the side chains
determine the behavior of these amino acids in proteins. Glycine being the smallest amino
acid often occurs where peptides chains bend sharply. Amino acids with hydrophobic R
groups (alanine, valine, leucine and isoleucine and aromatic R groups of phenylalanine,
tyrosine, and tryptophan) occur primarily in the interior of cytosolic proteins. Proline because
of the rigid ring structure is often found on bends of folded proteins. The charged R groups of
basic and acidic amino acids stabilize specific protein conformation via ionic interactions, or
salt bonds. Histidine plays an important role in enzymatic catalysis. At pH 7.0 it can function
as either a base or an acid catalyst. The primary alcohol group (-OH) of serine and the primary
thiol (–SH) group of cysteine are nucleophiles (electron rich)and can function during
enzymatic catalysis. The –OH groups of serine, threonine and tyrosine participate in enzyme
regulation. The aromatic rings of phenylalanine, tyrosine and tryptophan contain delocalised
electron clouds which enable them to interact other systems and transfer electrons. Amino
acids do not absorb visible light and are thus colourless. But tyrosine, phenyalanine and
tryptophan because of conjugated double bonds they have absorb high-wavelength (250 –
290 nm) ultraviolet light. Tryptophan makes a major contribution to the ability of most
proteins to absorb light in the region of 280 nm (Harper 2003: 18).

17
Amino acids have many functions in the body. Among the main functions are:
• They are monomer units for polypeptide chains of proteins
• They participate in nerve transmission
• They participate in biosynthesis of purines, pyrimidines, porphyrins and urea
• Short polymers of amino acids called peptides participate in the neuroendocrine
systems as hormones, hormone releasing factors, neurotransmitters

Amino acids are linked by peptide bonds to form polypeptide chains.

As mentioned above amino acids are monomer units for synthesis of polypeptide chains and
proteins. Details of how the process occurs will be discussed under the topic of protein
synthesis but at this stage you should know the bonds that are formed between amino acids.
In proteins the α–carboxyl group of one acid is joined to the α–amino group of another amino
acid to form a peptide bond (amide bond) with loss of a water molecule – condensation (Fig.
2.7)

Carboxyl
group for
activation

Peptide bond

Fig. 2.7

The equilibrium of this reaction lies on the side of hydrolysis rather than synthesis – hence
biosynthesis of a peptide bond requires an input of energy. To synthesize a peptide bond the
carboxyl group must be activated and the energy for activation of a carboxyl group comes
from adenosine triphosphate (ATP).
Two amino acids are joined by a peptide bond to form a dipeptide
Three ‘ ‘ ‘‘ ‘‘ ‘’ ‘’ two peptide bonds to form a tripeptide
Peptides with more than 10 amino acid residues are termed polypeptides and when few amino
acids are joined, peptides are referred to as oligopeptides
The amino acid residue at the end with a free α–amino group is the amino-terminal

18
 (N-terminal) residue and one with a free carboxyl group is the carboxyl-terminal (C-
terminal) residue. If MW is more than 10,000, polypeptides may be referred to as proteins but
you should always remember that these terms are sometimes used interchangeably.

Some naturally occurring peptides have biologically important effects.

These range from dipeptides to many thousands of amino acid residues. These small peptides
generally exert their effects at low concentrations.
eg Vertebrate hormones like oxytocin which stimulates uterine contractions has 9 amino acid
residues residues; bradykinin which inhibits inflammation in tissues has 9 amino acid
residues. Mushroom toxin amanitin is also a small peptide, as are some antibiotics. Slightly
larger peptides include Insulin with two polypeptide chains (30 and 21 residues) held together
by disulfide bonds and glucagon (29 residues) which counters the effects of insulin

2.7 Please attempt the questions below.

1. List the structural components of amino acids.
2. Classify the amino acids into categories based on characteristics of the side chains or
R groups.
3. Explain how side chains determine properties of amino acids.
4. Explain why histidine is often found on active sites of enzymes.
5. What are the main functions of amino acids?
6. Explain why tyrosine is more polar than phenylalanine.

19
 UNIT 3

CARBOHYDRATES

3.1 Introduction
Carbohydrates are generally regarded as a source of energy for many body functions. As you
will come to realize soon, carbohydrates are vital for many other functions in our bodies.
There is no widely accepted definition of carbohydrates but generally they are polyhydroxyl
aldehydes or ketones or substances that yield such compounds on hydrolysis ("polyhydroxy"
= 2 or more OH groups) and have the general formula (CH2O)n where n is the number of
carbon atoms.

Basic structure of carbohydrates

I
(CH2O)n or H - C - OH
I
Normally we tend to think of carbohydrates as vital nutrients for provision of energy only.
The truth is carbohydrates have multiple roles in all forms of life. They function as energy
stores, fuels and metabolic intermediates. They are also important structural elements of
bacteria and plant cell walls. They also modify functions of certain proteins and lipids by
covalently combining with them. In the form of ribose and deoxyribose they are important
structural network of ribonucleic acid and deoxyribonucleic acid. Recent evidence suggests
that carbohydrate units on the cell surface play key roles in the cell-cell recognition.

3.2 Aim
The aim of the unit is to introduce you to the general properties and functions of
carbohydrates.

3.3 Objectives
By the end of this unit you should be able to:
1. Classify carbohydrates
2. Describe the functions of carbohydrates
3. Describe the properties of carbohydrates

3.4 Equipment needed

None

3.5 Other resources

a) http://www.biochem.arizona.edu/classes/bioc462/462a/lectures/08/Miyashita_carbohy

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 drate.pdf
b) http://medicalppt.blogspot.com/search/label/biochemistry

3.6 Content
Classification
Carbohydrates are divided into four major classes:
Monosaccharides
Monosaccharides are the simplest form of sugar and are usually colorless, water-soluble,
crystalline solids. Some monosaccharides have a sweet taste. They can not be hydrolyzed into
simpler form. With few exceptions (e.g., deoxyribose), monosaccharides have the chemical
formula Cx(H2O)y, where x is at least 3. Monosaccharides can be classified by the number x of
carbon atoms they contain: triose (3) tetrose (4), pentose (5), hexose (6), heptose (7), and so
on. The simplest monosaccharides of biological significance have n=3. These are trioses
glyceraldehyde and dihydroxyacetone. Examples of heptoses include the ketoses
mannoheptulose and sedoheptulose. Monosaccharides with eight or more carbons are rarely
observed as they are quite unstable. The monosaccharides may be classified as aldoses or
ketoses depending upon whether the aldehyde or ketone functional group is present eg
glucose has an aldehyde group so its an aldose and fructose has a ketone group and it is a
ketose (Fig. 3.1).A ketone is any class of organic molecules that contain a carbonyl group
(C=O) in which the carbonyl group is bonded only to carbon atoms (see structures below).
An aldehyde is an organic compound containing a formyl group. This functional group, with
the structure R-CHO, consists of a carbonyl centre bonded to hydrogen and an R group.
Aldehydes differ from ketones in that the carbonyl in aldehydes is placed at the end of a
carbon skeleton rather than between two carbon atoms (Lehninger 2008: 239)(Stryer 2002
453).

H O
C CH 2OH
Aldehyde group
H C OH C O
Ketone group
HO C H HO C H
Fig. 3.1
H C OH H C OH

H C OH H C OH

CH2OH CH2OH

D-glucose D-fructose

Many carbon atoms in carbohydrates have four different groups linked to them. For instance
in glucose the 5th carbon from the aldehyde group has four different groups linked to it i.e. H,
OH, -CH2OH and the rest of the molecule. When a carbon atom is linked to four different
groups it is referred to as a chiral carbon. Depending on the orientation of the OH group on
the chiral carbon furthest from the aldehyde or ketone group the monosaccharide can be either
a D- or L- sugar. For sugars with more than one chiral center, D or L refers to the asymmetric
carbon furthest from the aldehyde or keto group (Fig. 3.2). Most naturally occurring sugars
are D isomers.

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 O H O H
C C
H – C– OH HO – C – H
HO – C – H H– C – OH
Fig. 3.2
H – C – OH HO – C – H
H – C – OH HO – C – H
Asymmetry of the
CH2OH CH2OH carbon atom furthest
D-glucose L-glucose from the aldehyde
group determines the
configuration of
glucose

Disaccharides
Disaccharides yield two molecules of the same or of different monosaccharides on hydrolysis.
For insitance hydrolysis of sucrose yields glucose and fructose, hydrolysis of lactose yields
galactose and glucose and hydrolysis of maltose yields two glucose molecules.
Oligosaccharides
Oligosaccharides yield 3-6 monosaccharide units on hydrolysis. Oligosaccharides in most
cells do not occur as free entities but are joined to nonsugar molecules (lipids and proteins) to
form glycoconjugates.

Monosaccharides, disaccharides and oligosaccharides are water soluble because of high

hydrogen binding potential.

Polysaccharides
Polysaccharides yield more than 6 molecules of monosaccharide on hydrolysis. They may be
linear or branched. Many polysaccharides are insoluble because their large size increases the
opportunity for intermolecular interactions i.e. molecules tend to interact more strongly with
each other than with water.

Glycogen
Glycogen is the main storage polysaccharide in animal cells. It’s a very large branched
polymer of glucose. A polymer of (α1→4)-linked subunits of glucose which means a carbon
atom at position 1 of one glucose molecule is covalently linked to another carbon atom at
position 4 of another glucose molecule. The branching occurs when a carbon atom at position
1 of one glucose molecule is covalently linked to another carbon atom at position 6 of another
glucose molecule to form α1→6 glycosidic bonds (Fig. 3.3). Branches occur about once in ten
glucose units of the chain. This branching increases the solubility of glycogen and makes its
sugar units accessible for addition of more glucose residues or release of more glucose
residues. Glycogen is mainly stored in the liver and muscle. Glucose can not be stored in its
monomeric form because the concentration of glucose in the cells that would be equivalent to

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stored glycogen is too high, and this can lead to osmotic destruction of the cells and the free-
energy change for entry of glucose into the cells against the concentration gradient would be
prohibitively large.

CH2OH C H2OH
glycogen
H O H H O H Fig. 3.3 Structure of glycogen
H H
OH H OH H 1
O
OH
O
H OH H OH

CH2OH CH2 OH 6 CH2 CH 2OH CH 2OH

H O H H O H H 5 O H H O H H O H
H H H H H
OH H OH H OH H 1 4 OH H OH H
4
O O O O OH
OH
3 2
H OH H OH H OH H OH H OH

Starch
Starch is a nutritional reservoir in plants. There are two types of starch i.e. Amylose (10-30%)
which is unbranched and the glucose residues are linked by α1→4 bonds as in glycogen above
and amylopectin (70-90%) which is branched and has about one α1→6 linkage per 30 α1→4
linkages (like glycogen except for the lower degree of branching). Both amylose and
amylopectin are hydrolyzed by α –amylase (found in human saliva). α –amylase hydrolyzes
internal α1→4 linkages to yield maltose (2 glucose residues in α1→4 linkage), maltotriose (3
glucose residues in α1→4 linkages), and α-dextrin (several glucose units joined by an α1→6
linkage in addition to α1→4 linkages). Maltose and maltotrioses are hydrolyzed to glucose by
maltase. α-dextrin is hydrolyzed to glucose by α-dextrinase.

Dextran
Dextran is the storage polysaccharide in yeasts and bacteria and consists only of glucose
residues. Nearly all linkages are α1→6 but occasional branches are formed by α1→2, α1→3
α1→4 depending on species. Dextrans formed by bacteria are components of dental plaque.

Peptidoglycan
Bacteria cell walls contain peptidoglycans which are linear polysaccharide chains that are
cross-linked by short peptides (Fig. 3.4). The rigid component of the bacteria cell walls is a
heteropolymer of alternating β1→4 – linked N-acetylglucosamine and N-acetyl muramic acid
residues. The linear polymers lie side by side in the cell wall cross-linked by short peptides.

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 Fig. 3.4 Structure of peptidoglycan
Gram positive bacteria like staphylococcal aureus have a pentaglycine chain in the cross link.
The cross-links hold the polysaccharide chains into a strong sheath that envelope the entire
cell and prevents cellular swelling and lysis due to osmotic entry of water. The enzyme
lysozyme kills bacteria by hydrolyzing the β1→4 linkages. Penicillin and other related
antibiotics kill bacteria by preventing synthesis of cross links leaving the cell wall too weak to
resist osmotic lysis.

Glycosaminoglycans
Glycosaminoglycans are anionic polysaccharide chains made of repeating disaccharide units.
The extracellular space in the tissues of multicellular animals is filled with a gel-like
extracellular matrix. This extracellular matrix is composed of an interlocking meshwork of
heteropolysaccharides (Glycosaminoglycans) and fibrous proteins such as collagen, elastin,
fibronectin etc. In glycosaminoglycans one of the two monosaccharides in repeating
disaccharide unit is always either N-acetylglucosamine or N-acetylgalactosamine and the
other is in most cases a uronic acid, usually D-glucuronic acid. At least one of the sugars in
the repeating unit has a negatively charged carboxylate or sulfate group. In some cases one or
more hydroxyls of the amino sugar is esterified with sulphate. The combination of sulfate
groups and carboxylate groups of the uronic acid residues gives glycosaminoglycans a very
high density of negative charge. To minimize repulsive forces among neighbouring groups
these molecules assume an extended conformation in solution. When brought together they
slip past each other like like-poles of a magnet. Squeezing water out of glycosaminoglycans
decreases their volume. On releasing the compression they return back to their original
hydrated state. Glycosaminoglycans are attached to extracellular proteins to form
proteoglycans. They have the ability to bind large amounts of water to form gel like matrix

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that forms the basis for the body’s ground substance. With a strong ground substance they
stabilize and support cellular and fibrous components. Since glycosaminoglycans can absorb
large quantities of water, they help maintain water and salt balance. The strong negative
charge on their surfaces also helps to mediate cell to cell interactions. Synovial fluid
glycosaminoglycans serve as lubricants in joints, tendon sheaths. Examples of
glycosaminoglycans are hyaluronic acid, condroitin sulphate, dermatan sulphate, keratan
sulfates, heparin(Harper 2003:109).

Glycoconjugates (Proteoglycans, Glycoproteins and Glycolipids).

These are carbohydrates that are covalently linked to other biomolecules like proteins and
lipids. Recall that among the functions of carbohydrates are able to bind covalently to proteins
and lipids to modify their functions. So glycoconjugates are a result of carbohydrates
covalently linked to other macromolecules. Proteoglycans, and glycoproteins are the two
types of sugar containing proteins.
Proteoglycans
Proteoglycans are macromolecules on the cell surface or extracellular matrix in which one or
more glycosaminoglycans are joined covalently to a membrane protein or secreted protein.
They are long, linear unbranched polysaccharides with a disaccharide repeating unit. The
glycosaminoglycan moiety commonly forms the greater mass, dominates the structure and is
often the main site of biological activity and biological activity involves provision of multiple
binding sites such as hydrogen bonding and electrostatic interactions with other proteins or the
extracellular matrix. Proteoglycans are major components of connective tissue such as
cartilage in which interactions with other proteoglycans, proteins and glycosaminoglycans
provide strength and resilience.
Glycoproteins
Glycoproteins have short oligosaccharides, which are highly branched and do not contain
disaccharide repeating units. Oligosaccharides are linked by a glycosidic bond between N-
acetylgalactosamine(GalNAc) and the hydroxyl group of serine and threonine (O-linked) eg
many membrane proteins and proteins in mucous secretions. Through the N-glycosidic link
oligosaccharides are covalently bonded to the amide nitrogen of an asparagine residue (N-
linked). All N-linked oligosaccharides chains are typically branched from a common core of 3
mannose and 2 GlcNAc. May be high mannose containing only 2 GlcNAc and up to 9
mannose units or consist of complex chains with sialic acid and or fucose. Many of the
proteins secreted by eukaryotic cells are glycoproteins eg antibodies and some hormones like
luteinizing hormone, follicle stimulating hormone etc. Some glycoproteins have a single
oligosaccharide chain but many have more than one. Oligosaccharides on glycoproteins
stabilize the proteins against denaturation, protect proteins from proteolytic cleavage, enhance
the solubility of proteins and serve as recognition signals for transport and cell-cell
interactions. The number of possible combinations of monosaccharide types and glycosidic
linkages in an oligosaccharide is large. Eg two identical hexoses can be linked to each other in
many different ways ( α1,2; α1,4; β1,2; β1,4 etc). In contrast two identical amino acids can be
linked in one way alanine-alanine – one peptide bond. Therefore carbohydrate structures have
greater structural diversity and therefore have potential to carry more information than
proteins of similar size. Each combination on oligosaccharides represents a unique face that is

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recognisable by different enzymes and receptors that interact with it. The same protein from
different tissues can have different glycosylation patterns, suggesting that oligosaccharide
chains may represent a tissue specific marker. Viscous properties of mucins derive from the
high content of negatively charged sialic acid residues. In mucins, the O-linked
oligosaccharides are usually short branched structures containing sialic acid, galactose,
GalNAc and sometimes other sugars like GlcNAc and L-fucose. Salivary mucin contains a
high number of serine and threonine residues and many are glycosylated as shown above. O-
linked oligosaccharides are negatively charged because of a high number of sialic acid
residues. When sialic acid residues are present in clusters they repel each other and prevent
protein folding. The result is the protein assumes an extended state, yielding viscous (mucous)
solutions. Mucus forms a protective layer on the surface of epithelial cells, lubricates surfaces,
facilitates transport processes eg movement of food in the gut (Lehninger 2008:255).

Glycolipids and lipopolysaccharides are membrane components

Glycolipids
Some lipids have covalently bound oligosaccharides. Oligosaccharide moieties are generally
found on the outer face of the plasma membrane. Gangliosides are membrane lipids of
eukaryotic cells in which the polar head group, the part that forms the outer surface of the
membrane is a complex oligosaccharide containing an acidic sugar N-Acetylneuraminic acid
(sialic acid) and other monosaccharide residues. Some oligosaccharide moieties of
gangliosides such as those that determine human blood groups are identical with those found
in certain glycoproteins
Lipopolysaccharides are the dominant surface feature of the outer membrane of gram-negative
bacteria. Lipopolysaccharides are important targets of the antibodies produced in response to
bacterial infection and are important determinants of bacterial strain. Lipopolysaccharides
produced by some bacteria are toxic to humans and when they are released in circulation they
can cause a toxic shock syndrome with low blood pressure (Lehninger 2008:256).

3.7 Please attempt the questions below

1. Classify carbohydrates on the basis of their strucutre
2. What are the functions of carbohydrates
3. Explain the difference between proteoglycans and glycoproteins
4. Explain why the enzyme lysozyme is bacteriocidal
5. Why do glycosaminoglycans have a high density of negative charge and what is the
importance of this?

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Summary of module 1
Water is the most abundant chemical in the body. It has characteristics that make it an ideal
solvent. A water molecule is a very small, so it moves fast and can squeeze into tiny
crevasses between other molecules. Because of its polarity it is easy for water to pry apart
other charged molecules, dissolving them; that is why it’s referred to as the Universal Solvent.
Due to its polarity water forms a crystalline structure that is less dense than liquid water.
Water has also got a unique heat capacity which enables it to absorb and release heat energy
slowly, and hold a great deal of heat energy. This helps organisms to maintain their body
temperature in the safe range. Polarity allows water to stick to itself (cohesion) and to any
charged material (adhesion). Water is also able to act as a buffer or acid in the body and this
helps to maintain constant pH. Amino acids are monomer units of peptides and proteins. They
have different characteristics depending upon the composition of the side chain or R- group.
For instance amino acids with polar hydrophobic side chains tend to be found in the interior of
folded proteins where they stabilize structures through hydrophobic interactions and the
amino acids with charged or polar side chains are found mostly on the outside of folded
proteins where they interact favorably with water. Carbohydrates are a versatile class of
molecules. They are the major form of stored energy in organisms and are the metabolic
precursors of many other biomolecules. Carbohydrates linked to lipids (glycolipids) are
components of biological membranes. Carbohydrates linked to proteins (glycoproteins) are
components of cell membranes and function in cell type recognition. Carbohydrates are in
four main groups; the monosaccharides, disaccharides, oligosaccharides and polysaccharides
depending upon the number of monomer units in each group. Polysaccharides can be formed
from same monosaccharides or different monosaccharides.

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