BCH 3000

PRINSIP BIOKIMIA
FOR PJJ
(Semester 1 -2013/14)

1
Kod/Nama Kursus : BCM 3000 (4+0)
(Biokimia Asas)
Nama Pensyarah : Prof. Dr. Mohd Arif
Syed (MAS) -Penyelaras
Prof. Dato’ Dr. Abu Bakar
Salleh (ABS)
Jabatan : Biokimia
Jadual Kuliah
( Masa dan Tempat) :

2
 Sinopsis
(This course encompasses the main
biomoleculer components in biochemistry.
Metabolism involving the anabolism and
catabolism of major biomolecules are also
explained)

3
 Learning Outcome
1. Distinguish the structure and function of
biomolecules found in biological systems (C4)
2. State the various key metabolic processes (P2)
3. Describe the biochemical reactions (A3)
4. Solve problems related to the metabolism of
biomolecules by using information from various
sources (CTPS, LL)

4
 Brief Lecture Contents
1. Introduction-Biochemistry? Contributions? Important
life components
2. Carbohydrates – Classification – mono, di
polysaccharides – Structure –configuration &
stereochemistry; reactions – glucose and other sugars
3. Amino acid & protein – biological roles, structure,
classification, reactions, analysis. Peptides – primary,
secondary, tertiary and quaternary structures
4. Lipid –functions & distribution, characteristics of fatty
acids-saturated & unsaturated f/acids. Structures &
characteristics of triacylglycerols, phospholipids,
sphingolipids, terpenes & steroids

5
 Brief Lecture Contents
5. Nucleic acids – components – purines, pyrimidines.
Structure, reactions & importance of nucleosides,
nucleotides & polynucleotides. DNA, RNA – structure,
functions & types
6. Enzymology – Classification, naming, active sites. Enzyme
kinetics. Factors affecting enzyme activity- enzyme &
substrate concentration, pH, temperature . Substrate
specificity – single & multiple substrate. Enzyme inhibitors
– competitive, con-competitive, uncompetitive. Control of
enzyme reactions – product inhibition, Isoenzymes,
multienzyme system and allosteric enzymes

6
 Brief Lecture Contents
7. Carbohydrate metabolism – Metabolic energy cycle –
Bioenergetics: ATP other high energy compounds.
Storage & energy transfer. Glycolysis & fermentation.
Electron transport system. Compartmentation &
mitochondria. Phosphorylation & production of ATP.
Anaplerotic reactions. Glyoxylate cycle.
Gluconeogenesis. Pentose phosphate pathway.
Integration and control.
8. Photosynthesis – Fixation of CO2 during
photosynthesis. Chlorophyll, components of
photosynthesis. Photosystem I & II.
Photophosphorylation. Calvin cycle. Hatch-Slack
cycle.

7
 Brief Lecture Contents
9. Lipid metabolism – Lipid oxidation- Enzymes involved,
energy production. Oxidation of saturated & branched
fatty acids. Formation of ketone bodies. Lipid
biosynthesis –mitochondrial system and extra-
mitochondrial. Cycle & enzymes involved. Synthesis of
saturated & unsaturated fatty acids. Cholesterol
synthesis & control.
10. Protein & amino acid metabolism – Degradation of
amino acids- transamination, deamination,
decarboxylation. Cycle involved- intermediates for the
TCA cycle. Ammonia and urea metabolism. Biosynthesis
of amino acids- role in the metabolism of porphyrin and
nucleic acids. Nitrogen fixation.

8
 Brief Lecture Contents
11. Nucleic acid metabolism – synthesis of
mononucleotides – purines, pyrimidines – cycle and
enzymes involved; control. Biosynthesis of ribo &
deoxyribonucleotides. Characteristics of genetic
materials – chromosomes. Genetic code, base
sequence. DNA replication. DNA repair. Protein
synthesis – ribosome, co-factor involved & phase of
synthesis. Inhibition and control of synthesis.
12. Membrane Biochemistry – Modification & structure.
Model for membrane structure. Transport mechanism
across membrane – passive & active transport.

9
 Brief Lecture Contents
13. Hormones- Introduction to plant & animal hormones.
Reactions & control of endocrine hormones. Hormone
reactions at the molecular level.
14. Integration & control of metabolism. Relationship
between carbohydrate, lipid and protein metabolism.

10
 Course Evaluation
1. Mid Term = 35%
(17% + 18%)
1. Final Exam = 35%
2. SCL = 30%
Total = 100%

11
 Course Evaluation

1. Mid Term 35%

(17% + 18%)
2. SCL 30%
i. Model and 20%
presentation
ii. Assignment 10%
3. Final Examination 35%
TOTAL 100%

12
 Course Evaluation
Mid Term = 35% - 2013
Topics covered in test
1. Introduction-Biochemistry
2. Carbohydrates
3. Amino acid & protein
4. Lipid
5. Nucleic
6. Enzymology

13
 Course Evaluation
Mid Term = 35% -
Types of Questions
1. Duration – 2 hours
2. Multiple choice – 60 questions (1 mark each)
3. Short Answers - Choose 8 out of 10 questions ; 5
marks each

14
 Course Evaluation
Final Examination = 35%
Topics covered in exam
7. Carbohydrate metabolism
8. Photosynthesis
9. Lipid
10. Protein & amino acid metabolism
11. Nucleic acid metabolism
12. Membrane
13. Hormones
14. Integration & control of metabolism
15
 Course Evaluation
SCL (Student Centered Learning = 30%
1. MODEL AND PRESENTATION

In this exercise, each student is required to produce a

model of an oligopeptide using materials from the
environment. The model should be able to demonstrate
clearly the structural configuration of the oligopeptide .
The student will be asked to present the model and
explain the structural configuration

16
 Course Evaluation
SCL (Student Centered Learning = 20%
Model Requirements
1. The student must design and produce a model of an
oligopeptide
2. All amino acids must be different from one another and
of different group
3. Materials used must be from the environment. No model
kit will be allowed. This is also not computer modeling
4. The model should clearly show the structure of the amino
acid
5. Student will be asked to explain their respective models

17
 Course Evaluation
SCL (Student Centered Learning = 25%
PRESENTATION
1. Week 14 (The latest date. Can be arranged)
2. Place – Biotek 1
3. Date – please inform when you are available
4. Evaluation by a panel

18
19
 BCH 3000
PRINSIP BIOKIMIA

(Semester 1 -2012/13)

20
Kod/Nama Kursus : BCM 3000 (4+0)
(Biokimia Asas)
Nama Pensyarah : Prof. Dr. Mohd Arif
Syed (MAS) -Penyelaras
Puan Zetty
Jabatan : Biokimia
Jadual Kuliah
( Masa dan Tempat) : SK 10-12; DKBiotek 1.1

21
 Sinopsis
(This course encompasses the main biomolecule
components in biochemistry. Metabolism
involving the anabolism and catabolism of
major biomolecules are also explained)

22
 Learning Outcome
1. Membezakan struktur dan fungsi biomolekul yang
terdapat dalam sistem biologi (C4)
2. Menyatakan pelbagai proses metabolisme yang
utama (P2)
3. Menerangkan tindakbalas biokimia (A3)
4. Menyelesaikan masalah dalam metabolisme
biomolekul dengan menggunakan maklumat dari
pelbagai sumber (CTPS, LL)

23
 Brief Lecture Contents
1. Introduction-Biochemistry? Contributions? Important
life components
2. Carbohydrates – Classification – mono, di
polysaccharides – Structure –configuration &
stereochemistry; reactions – glucose and other sugars
3. Amino acid & protein – biological roles, structure,
classification, reactions, analysis. Peptides – primary,
secondary, tertiary and quaternary structures
4. Lipid –functions & distribution, characteristics of fatty
acids-saturated & unsaturated f/acids. Structures &
characteristics of triacylglycerols, phospholipids,
sphingolipids, terpenes & steroids

24
 Brief Lecture Contents
5. Nucleic acids – components – purines, pyrimidines.
Structure, reactions & importance of nucleosides,
nucleotides & polynucleotides. DNA, RNA – structure,
functions & types
6. Enzymology – Classification, naming, active sites. Enzyme
kinetics. Factors affecting enzyme activity- enzyme &
substrate concentration, pH, temperature . Substrate
specificity – single & multiple substrate. Enzyme inhibitors
– competitive, con-competitive, uncompetitive. Control of
enzyme reactions – product inhibition, Isoenzymes,
multienzyme system and allosteric enzymes

25
 Brief Lecture Contents
7. Carbohydrate metabolism – Metabolic energy cycle –
Bioenergetics: ATP other high energy compounds.
Storage & energy transfer. Glycolysis & fermentation.
Electron transport system. Compartmentation &
mitochondria. Phosphorylation & production of ATP.
Anaplerotic reactions. Glyoxylate cycle.
Gluconeogenesis. Pentose phosphate pathway.
Integration and control.
8. Photosynthesis – Fixation of CO2 during
photosynthesis. Chlorophyll, components of
photosynthesis. Photosystem I & II.
Photophosphorylation. Calvin cycle. Hatch-Slack
cycle.

26
 Brief Lecture Contents
9. Lipid metabolism – Lipid oxidation- Enzymes involved,
energy production. Oxidation of saturated & branched
fatty acids. Formation of ketone bodies. Lipid
biosynthesis –mitochondrial system and extra-
mitochondrial. Cycle & enzymes involved. Synthesis of
saturated & unsaturated fatty acids. Cholesterol
synthesis & control.
10. Protein & amino acid metabolism – Degradation of
amino acids- transamination, deamination,
decarboxylation. Cycle involved- intermediates for the
TCA cycle. Ammonia and urea metabolism. Biosynthesis
of amino acids- role in the metabolism of porphyrin and
nucleic acids. Nitrogen fixation.

27
 Brief Lecture Contents
11. Nucleic acid metabolism – synthesis of
mononucleotides – purines, pyrimidines – cycle and
enzymes involved; control. Biosynthesis of ribo &
deoxyribonucleotides. Characteristics of genetic
materials – chromosomes. Genetic code, base
sequence. DNA replication. DNA repair. Protein
synthesis – ribosome, co-factor involved & phase of
synthesis. Inhibition and control of synthesis.
12. Membrane Biochemistry – Modification & structure.
Model for membrane structure. Transport mechanism
across membrane – passive & active transport.

28
 Brief Lecture Contents
13. Hormones- Introduction to plant & animal hormones.
Reactions & control of endocrine hormones. Hormone
reactions at the molecular level.
14. Integration & control o f metabolism. Relationship
between carbohydrate, lipid and protein metabolism.

29
 BCH3000 - SKEDUL KULIAH
Sep-12 Oct-12 Nov-12
MINGGU 1 2 3 4 5 6 7 8 9 10 11 12
Monday 3 10 17 24 1 8 15 22 29 5 12 19 26
Tuesdsay 4 11 18 25 2 9 16 23 30 6 13 20 27
Wednesday 5 12 19 26 3 10 17 24 31 7 14 21 28
Thursday 6 13 20 27 4 11 18 25 1 8 15 22 29
Friday 7 14 21 28 5 12 19 26 2 9 16 23 30
Saturday 1 8 15 22 29 6 13 20 27 3 10 17 24
Sunday 2 9 16 23 30 7 14 21 28 4 11 18 25

Dec-12 Jan-13 Feb-13

MINGGU 13 14 15
Monday 31 3 10 17 24 7 14 21 28 4 11 18 25
Tuesdsay 4 11 18 25 1 8 15 22 29 5 12 19 26
Wednesday 5 12 19 26 2 9 16 23 30 6 13 20 27
Thursday 6 13 20 27 3 10 17 24 31 7 14 21 28
Friday 7 14 21 28 4 11 18 25 1 8 15 22
Saturday 1 8 15 22 29 5 12 19 26 2 9 16 23
Sunday 2 9 16 23 30 6 13 20 27 3 10 17 24

Kuliah
Cuti- Alexandria
Cuti Pertengahan Semester
Peperiksaan Akhir 30
Cuti Umum
 Why study biochemistry?
● Part of curriculum
● Explain a lot of the controversies in the news at the
moment.

Stem cell study

Cloning of the human being

Diseases (defect in metabolism)

GM food and organisms (genetically modified)

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BIOCHEMISTRY: A PROLOGUE

Biochemistry = the chemistry of life.

● ∴ bridges the gap between chemistry (the study of
the structures and interactions of atoms and
molecules) and biology (the study of the structures
and interactions of cells and organisms).
● Since living things are composed of inanimate
molecules, life, at its most basic level, is a
biochemical phenomenon.

Inert; not living; not lively

32
 Living organisms
● diverse in their macroscopic properties
● BUT remarkable similarity in their biochemistry that
provides a unifying theme with which to study
them.
◊ For example, hereditary information is encoded
and expressed in an almost identical manner in
all cellular life
◊ the series of biochemical reactions= metabolic
pathways, as well as the structures of the
enzymes that catalyze them are, for many basic
processes, are nearly identical from organism to
organism.
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 This strongly suggests that all known life forms are
descended from a single primordial ancestor in
which these biochemical features first developed

34
Although biochemistry is a highly diverse field, it is
largely concerned with a limited number of interrelated
issues. These are

1. What are the chemical and three-dimensional

structures of biological molecules and assemblies,
how do they form these structures, and how do their
properties vary with them?
2. How do proteins work?- what are the molecular
mechanisms of enzymatic catalysis, how do receptors
recognize and bind specific molecules, and what are
the intramolecular and intermolecular mechanisms
by which receptors transmit information concerning
their binding states?

35
3. How is genetic information expressed and how is it
transmitted to future cell generations?
4. How are biological molecules and assemblies
synthesized?
5. What are the control mechanisms that coordinate
the myriads of biochemical reactions that take place
in cells and in organisms?
6. How do cells and organisms grow, differentiate, and
re-produce?

36
 History of Biochemistry

● fairly new field of science -the 20th century

● first landmark of biochemistry - Friedrich Wohler (1828)
synthesized the organic compound urea from the
inorganic compound ammonium cyanate
● ∴building blocks of life were the same as those of non-
living things
● The role of enzymes as catalyst - Buchner showed that a
process of biochemistry, catalysis, could occur
independently from living cells (enzymes in yeast extracts
and fermentation)

37
 History of Biochemistry

● Fischer developed the lock and key model (enzyme as

rigid lock, substrate as key) A modified version of this
model (induced fit) is still used today
● The second part of the 20th century saw advances in
structural biology especially the structure of proteins
● The first protein structures were determined by John
C. Kendrew and Max Perutz in the 1950s and 1960s.
● Now have determined the structures of more than
1000 proteins.

38
39
 History of Biochemistry
● The role of nucleic acid as information molecules

In 1944 Oswald Avery et al extracted DNA from a
toxic strain of a bacteria and when added to a
nontoxic strain resulted in the bacteria being
transformed into a virulent strain.

Watson and Crick (1950) deduced the 3D structure
of DNA.

Crick predicted that information encoded in DNA is
transcribed to ribonucleic acid and then translated
to protein.

This unidirectional information flow is referred to
as the central dogma of molecular biology
40
 BIOLOGICAL STRUCTURES
Living things are enormously complex.
● simple E. coli cell contains some 3 to 6 thousand
different compounds, most of which are unique to E.
coli ; Homo sapiens (human beings), may contain
100,000 different types of molecules, although only a
minor fraction of them have been characterized.
● ∴ biochemical understanding of any organism would
be a hopelessly difficult task ??

 No !!!! - Why ????

41
Living things have an underlying regularity that derives
from their being constructed in a hierarchical manner.

Multicellular organisms

Organizations of organs

Tissues

Cells

Subcellular organelles

Supramolecular assemblies of
macromolecules 42
An example of hierarchical
organization of biological
structures
43
What makes a living
thing?

44
 The Chemical Elements of Life
● Only six nonmetallic elements make up 97% of the
weight of most organisms – carbon, oxygen,
hydrogen, nitrogen, phosphorous and sulfur.
● All form stable covalent bonds.
● here are also 5 common ions found in all organisms:
- Calcium (Ca2+), Potassium (K+) Sodium (Na+),
Magnesium (Mg2+), Chloride (Cl-)
● Water is a major component of cells.
● Altogether, a total of 29 different elements are
commonly found in living organisms.

45
Brown – important elements
purple – essential ions
dark blue – more common trace elements
light blue – less common trace elements
46
 Organic compounds

● Most of the solid material of cell consists of carbon-

containing compounds (∴ ∴organic compounds).
● The organic compounds of interest is shown

47
 Functional Groups

● These organic compounds have own specific

functional groups

48
● The elements of life are assembled into molecules
with common structures and patterns – how ?? –
via linkages (bonds)

49
The polymeric organization of proteins, nucleic
acids an dpolysaccharides
50
 BIOPOLYMERS

● they are formed from smaller molecules called

monomers that are linked together in a sequential
way to form long chains
● After being joined together, the individual monomers
in a chain are referred to as residues
● There are various levels in the hierarchy of life i.e.
atoms, molecules, biopolymers, organelles, cells,
tissues, organs and whole organisms

51
 PROTEINS
An example of a biopolymer

● polymers formed from the condensation of individual

monomers called amino acids
● Twenty amino acids are incorporated into proteins in
all cells
● Each amino acid contains an amino group and a
carboxylate group and a side chain (R group).
● The amino group from one amino acid reacts with the
carboxylate group of the other to form an amide
linkage that is referred to as a peptide bond

52
53
● Many amino acids joined in this manner is called a
polypeptide ( have N and C terminal
● The amino acids are combined in a specific
sequence to produce proteins consisting of
hundreds or thousands of amino acid residues

54
● A functional protein consist of one polypeptide or
several different polypeptides tightly bound
together.
● Proteins function as either enzymes or structural
components of cells and organisms.
● The function of a protein depends on the 3D
structure or conformation.

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BCM 3000
PRINSIP
BIOKIMIA

56
 POLYSACCHARIDES

● Composed basically of carbon, oxygen and hydrogen.

● Monosaccharides – simple sugars, polysaccharides –
polymers.
● Fischer projection – linear molecule.
● Haworth projection – ring form (usual biochemical
form).
● Ribose – approx. 20 conformations

57
● Glucose –
o most abundant six-carbon sugar
o Monomer for cellulose, glycogen and starch
o Differ in bonding between C-1 of the monomer
to the next

58
59
 Nucleic acids

● Biopolymers of monomers called nucleotides.

● Nucleotides – five-carbon sugar, heterocyclic nitrogen
base and at least one phosphate.
o Five – carbon sugar (ribose and deoxyribose).
o Base (purines and pyrimidines).
 Purines – adenine (A) and guanine (G).
 Pyrimidines (cytosine ( C), thymine (T) and
Uracil (U)

60
Nucleic acids are polymers formed from monomers
called nucleotides that are joined in a phosphodiester
linkage

Polynucleotide-
formed by linking
phosphate group to
C-3 oxygen atom of
another nucleotide

61
 Examples of nucleic acids
1. DNA
● uses deoxyribose sugars
● Usually double stranded
2. RNA
● Uses ribose sugars
● Usually single stranded
● 4 types of RNA :
i. mRNA
ii. tRNA
iii. rRNA
iv. heterogenous RNA.
62
 Lipids and Membranes

● Diverse class of compounds rich in carbon and

hydrogen (low in oxygen).
 Fatty acids, glycerophospholipids, wax and
beeswax.
● Most lipids not soluble in water.
● In membranes lipid are polar - hydrophilic water
loving head and hydrophobic (water fearing) tail.
● Form bi-layer membrane system.

63
 The Energetics of Life
● Life requires input of energy – ultimately from
the sun
● Metabolism
 Describes the numerous reactions in which
organic compounds are synthesized and
degraded and useful energy is extracted,
stored and used.
 Bioenergetics
o The study of the changes in metabolic
energy

64
● ∆G – the free-energy change for a reaction is the
difference between the free energy of the product and
the free energy of the reactants.
∆G = ∆H - T ∆S
where
∆H is the change in heat content (enthalpy change)
∆S is the change in randomness (entropy change)
T is the temperature in Kelvin.

∆G < 0 reaction is spontaneous

∆G > 0 reaction requires input of energy
∆G = 0 reaction is at equilibrium.
65
 Metabolic Processes
● Many many types of chemical reactions simultaneously
occur in any living cell.
● Yet, these reactions follow a pattern that organizes
them into the coherent process we refer to as life.
o For instance, most biological reactions are
members of a metabolic pathway - sequence of
reactions that produce one or more specific
products.
o Moreover, the rates of its reactions are so tightly
regulated that there is rarely an unsatisfied need
for a reactant in a metabolic pathway or an
unnecessary buildup of some product.
66
Metabolism - traditionally divided into two major
categories:
1. Catabolism or degradation, in which nutrients and
cell constituents are broken down so as to salvage
their com-ponents and/or to generate energy.
2. Anabolism or biosynthesis, in which biomolecules
are synthesized from simpler components

The energy required by anabolic processes is provided

by catabolic processes largely in the form of adenosine
triphosphate (ATP).

67
68
 Expression and Transmission of Genetic
Information
● Deoxyribonucleic acid (DNA) is the cell's master
repository of genetic information
● Genetic information is encoded in the sequence of these
bases.
● The division of a cell must be accompanied by the
replication of its DNA.
◊ each DNA strand acts as a template for the
formation of its complementary strand
◊ ∴ every progeny cell contains a complete DNA
molecule each of which consists of one parental
strand and one daughter strand. Mutations arise
when, through rare copying errors or damage
69
repository is a place where data or specimens are
stored and maintained for future retrieval.

Encoded - prearranged; programmed, determined,

set,preset

Replication - duplication,copying, reproduction

70
 The cell is the basic unit of life

Cells are classified as eukaryotes or prokaryotes

1. Prokaryotes (bacteria)
 Ubiquitous, no nucleus, only approx 1000
genes

2. Eukaryotes (plants, animals, fungi and protists)

 Membrane bound nucleus, 1000 fold greater
in volume.

71
An animal cell 72
A plant cell 73
74
 Water

Properties
● All living cells depend on water for their
existence.
● Metabolic machinery of cells has to
operate in an aqueous environment
● Water molecule – polar
● Water molecule is V-shaped with an angle
of 104.5O

75
76
Oxygen atom
● has 8 electrons with 6 in the outer shell
● The outer shell can accommodate 4 sp3 orbitals.
 2 lone pairs containing 2 electrons each and 2
orbitals which can share their electron with the
electron in hydrogen

an oxygen atom covalently bonded to two
hydrogen atoms
 It has a tetrahedral bond structure that results from
4 sp3 hybridized orbitals
● The oxygen nucleus attracts electrons more strongly
than the single proton in hydrogen nucleus

77
78
Tetrahedral bond structure of water
79
 δ-) and a
● There is a small negative charge on oxygen (δ
δ +)
small positive charge on the hydrogen (δ
● Water forms hydrogen bonding (up to 4 hydrogen
bondings)

80
Noncovalent Interactions in Biomolecules

There are 4 types of noncovalent interactions.

1. Charge-charge interactions
● Electrostatic interactions between two charged
particles e.g. NaCl
● The strongest noncovalent forces
● Also responsible for mutual repulsion of similarly
charged ionic groups

81
2. Hydrogen bonds
● A type of electrostatic interaction which occurs
in many macromolecules
● Among the strongest noncovalent forces in
biological systems
● Strong enough to confer structural stability but
weak enough to be readily broken.
● Can form when a hydrogen covalently bonded
to a strong electronegative atom, such as
nitrogen, oxygen and sulfur

82
83
Hydrogen bonding

84
 3. Van der Waals Forces

● Weak intermolecular forces produced between all

neutral atoms by transient electrostatic interactions
● Have attractive and repulsive components
● forces that exist between MOLECULES of the same
substance

85
Van der Waals Forces
86
 4. Hydrophobic interactions

● The association of a relatively nonpolar molecule or

group in aqueous solution with other nonpolar molecules
rather than with water
● The non-polar groups mutually repel water and other
polar groups and results in a net attraction of the non-
polar groups for each other. Hydrocarbon alkyl groups on
ala, val, leu, and ile interact in this way

87
Hydrophobic interactions
88
Ionization of Water

● Important property of water – slight tendency to ionize.

● Pure water consist of H2O and small quantity of hydronium
ions (H3O+) and hydroxide ions (OH-)
● Important property of water – slight tendency to ionize.
● Pure water consist of H2O and small quantity of hydronium
ions (H3O+) and hydroxide ions (OH-)

89
The pH Scale
A logarithmic scale to measure the concentration of H+.

90
91
 AIR – H2O
Medium for biological system
∴ need to know the role in the degradation/dissociation
of ions from biomolecules
Water = neutral molecule, but it can ionise –

92
 AIR – H2O

From the dissociation/ionization of water
equation

pH = -log [H+]
ie. pH = negative log of hydrogen ion (H+)
concentration
pOH = negative log of hydroxyl ion (OH-)
concentration

93
 ACID
= substance that donates proton
 a substance which produces hydrogen ions
(H+) by dissociation

For example
HCl  H+ + Cl-
Hydrogen ions (H+) associate with
water to form H3O+ (Hydronium
ion)
94
 = Substances that receive proton
BASE = can associate with H+ (e.g. NH3)
= may produce hydroxide ions (OH- )
either by direct dissociation or
subsequent to reaction with water

i. KOH  K+ + OH-

NH3 + H2O  NH4OH  NH4+ + OH-

95
STRONG ACIDS are compounds that dissociate (ionize)
almost 100% in an aqueous solution.

HCl
H+ + Cl-

96
The common acids that are almost one
hundred percent ionized are:

HNO3 - nitric acid

HCl - hydrochloric acid
H2SO4 - sulfuric acid
HClO4 - perchloric acid
HBr - hydrobromic acid
HI - hydroiodic acid

97
WEAK ACIDS = Substances that dissociate
partially

HAc H+ + Ac-

98
Examples of strong bases
LiOH - lithium hydroxide
NaOH - sodium hydroxide
KOH - potassium hydroxide
RbOH - rubidium hydroxide
CsOH - cesium hydroxide
Mg(OH)2 - magnesium hydroxide
Ca(OH)2 - calcium hydroxide
Sr(OH)2 - strontium hydroxide
Ba(OH)2 - barium hydroxide

99
When a weak acid or base dissociates in an aqeous
solution, will get an equilibrium between the acid and its
conjugate base. This equilibrium is called

Equilibrium constant = Ka

Using this equilibrium and taking into consideration the

equation for the dissociation of weak acid, will get an
important equation called the Henderson-Hasselbalch
equation

pH = pKa + log [A-]

[HA]
100
 IONIZATION OF WATER

H2O + H2O H3O + + OH-

H2O H+ + OH ………… (1)

Law of Mass Action to get equilibrium point
(the rate of a chemical reaction is directly proportional
to the molecular concentrations of the reacting
substances )
Keq = [H+] [OH-] ..................... (2)
[H2O]

Keq = Equlibrium constant

[ ] = concentration in mole/liter (M)
101
If we know the value of Keq pure water
can determine
the values of [H+] dan [OH-]

Keq for pure water = 1.8 x 10-16M

[Water] = 55.5M

∴ 1.8 x 10-16 = [H+] [OH-]

55.5M

[H+] [OH-] = 1.0 x 10-14M .................... (3)

[H+] = [OH-] – equation (1)

∴[H+] = [OH-] = 1.0 x 10-14M

= 1.0 x 10-7M
102
In exponential form - (1.0 x 10-7M) too small
Simpler method – use - Svenson – pH dan pOH

pH = -log [H+]
pOH = -log [OH-]

Equation (3) becomes

log [H+] + log [OH-] = -14
-log [H+] - log [OH-] = 14
i.e. pH + pOH = 14

103
Because [H+] = [OH-]
pH = pOH = 7

pH = pOH = 7, solution is neutral

pH = pOH < 7, solution is acidic
pH = pOH > 7, solution is basic

104
 HENDERSON-HASSELBALCH EQUATION

For weak acid eg. CH3COOH (HA)

HA H+ + A-

In equilibrium conditions

Ka = [H+][A-] Ka = equilibrium constant

[HA]

[H+] = Ka [HA]
[A-]

105
 HENDERSON-HASSELBALCH EQUATION

log [H+] = log Ka + log [HA]

[A-]
- log [H+] = - log Ka + log [A-]
[HA]

- log [H+] = pH ; -log Ka = pKa

pH = pKa + log [A-]

[HA]
106
 pH = pKa + log [A-]
[HA]

pH = pKa + log [conjugate base]

[conjugate acid]

pH = pKa + log [proton acceptor]

[proton donor]

107
This equation is called the HENDERSON-
HASSELBALCH Equation

This equation is useful to determine

1. the amount of acid
2. the amount of base or
3. the amount of salt required to prepare a
buffer with the pH that we want

108
109
 BCH 3000
PRINCIPLES OF
BIOCHEMISTRY

(Semester 1 -2012/13)

110
 CARBOHYDRATE
• Carbohydrates as the main component of life
• Classification
• Structure
• Chemical reactions and biochemical functions of
carbohydrate

111
CARBOHYDRATE

112
113
 CARBOHYDRATES

● 'hydrate of carbon', with structural formula (CH2O)n

● Carbohydrate = saccharides = biological molecules
● The basic building blocks of carbohydrates are the
monosaccharides –i.e. simplest = monosaccharides,
eg. glucose
● These are linked together in longer chains to form
oligosaccharides (2 - 20 residues - eg. Maltose) and
polysaccharides (> 20 residues eg. starch, cellulose ,
glicogen )

114
 CARBOHYDRATES

● The root sacchar- comes from the Latin saccharum,

"sugar".
● Why saccharide called carbohydrate ?
 Most have general formula (CH2O)n
● Many saccharides
a. Modified
b. Contains amino groups, sulphates, phosphates,
etc.

115
 Functions of carbohydrates

● important source of energy for the body - 1g of

carbohydrate provides 4.2 kcal of energy
o Almost all of the cells use glucose to distribute
energy -brain cells ; erythrocytes (red blood
cells) are completely dependant on glucose as
an energy source.
● Act as energy storage - glycogen stores act as a
readily available energy reserve. A person weighing
70kg has a glycogen reserve of about 350 - 400g,
which is about 1.500 kcal.

116
 Functions of carbohydrates

● Carbohydrates find many uses as structural

elements – eg. Cellulose – cell walls in plants,
bacteria, exoskeleton of insects,
● Carbohydrates are utilized as raw materials for
several industries. For e.g., paper, plastics, textiles
etc.
● Marker molecules for cell recognition – Blood types
– A,B,O
● Found in biological molecules e g coenzymes and
nucleic acids

117
 Classification of Carbohydrates

1. Monosaccharide- one sugar residue. Most well

known is glucose, C6H12O6

2. Oligosaccharide- a few (2-9) sugar residues . Most

well known is cane sugar or sucrose, C12H22O11.

3. Polysaccharide - many sugar residues. Most

common are glycogen, starch and cellulose, from
animals, plants and plants.

118
 Monosaccharides

1. Two classes- aldoses (aldehyde) and ketoses (keto)

2. In our formula, (CH2O)n, n is 3 or more
3. Simplest are dihydroxycetone, a ketose where n=3,
and glyceraldehyde, an aldose where n=3 - Triose
4. Simple sugars – monomeric
5. can have different number of carbon atoms
6. can be combined to form disaccharides and
polysaccharides
7. some can have a linear or ring structure

119
 Monosaccharides

● Aldose = an aldehyde with two or more hydroxyl

groups.
● Ketose = a ketone with two or more hydroxyl groups
● Both are trioses = simplest monosaccharides; three-
carbon sugars
120
Aldehyde Ketone

back

121
Aldoses and Ketoses
122
 Monosaccharides
● Both have the same compositions = TAUTOMERS =
(isomer)
● Tautomers are organic compounds that are
interconvertible by a chemical reaction called
tautomerization.
● Can change from one form to the other but takes a
very long time
● Catalysts can speed up the change

Why tautomer ??
Change from one form (aldehyde) to another (ketone)
123
Isomers = are molecules

● with the same chemical formula

● and often with the same kinds of bonds
between atoms,
● but in which the atoms are arranged
differently.
● Many isomers share similar if not identical
properties in most chemical contexts

124
 ENANTIOMER (Optical isomers)
● In glycerldehyde – chiral carbon = 4
different groups
●  get 2 isomers = enantiomer
mirror
images which are not superimposable - D
and L isomer

125
126
127
128
Enantiomers -if they are –
● mirror images of each other- one is the mirror
image of the other,
● two stereoisomers are enantiomers if they are
different but each can be superimposed on
the mirror image of the other.
129
 Stereoisomers

● means that the two molecules differ in their

three-dimensional shapes only but that they
have the same structural formulas.
● This means they have the same exact groups
attached in the same way.
● Only the three-dimensional orientation of
these groups are different.
● ∴ enantiomers are stereoisomers

130
 Diastereomers (or diastereoisomers)

● are stereoisomers that are not enantiomers

(nonsuperimposable mirror images of each
other).
● can have different physical properties and
different reactivity.
● pairs of isomers that have opposite
configurations at one or more of the chiral
centers but are not mirror images of each other
● cis-trans isomerism is a form of diastereomerism

131
Diastereomers

132
133
QUESTION
Which is L isomer?
Which is D isomer?
 Fischer Projections
● Glyceraldehyde is actually the basis for the L
and D nomenclature
● Solution of D-glyceraldehyde rotates
polarized light to the right (dextrorotatory)
and L-glyceraldehyde rotates light to the left
(levorotatory)
134
Plane Polarized Light
135
136
137
138
 Fischer Projections

● Monosaccharides can have multiple chiral

centers
● ∴ need some conventions for drawing their
structures.
● For linear chains, the stereochemistry is
often represented as a Fischer Projection:

139
● In a Fischer projection the carbon chain is oriented in
the vertical direction, with a conformation that projects
the carbon bonds onto a flat plane, and with all
horizontal bonds projecting out, in front of the plane
● When the molecule is oriented with the C1 aldehyde at
the top, pointing away from the viewer, this defines a
convention where the C2 hydroxyl group will be on the
left for L-glyceraldehyde, and on the right for D-
glyceraldehyde
140
Stereochemistry of Longer Monosaccharides

i. For longer monosaccharides, the assignment of the L and

D configuration is determined by the configuration of the
chiral carbon farthest away from the C1 carbonyl (ie.
Highest chiral number)

ii. Eg. - glucose, a 6-carbon sugar, the C5 carbon is used. If

the C5 hydroxyl group is on the left, the molecule is L-
glucose. If the hydroxyl group is on the right, it is D-
glucose
iii. In a carbon chain with 2 possible configurations for each
chiral center, there are a total of 2n stereoisomers for a
compound with n chiral carbons
141
142
Some D-
Aldose
Isomers

143
Some D-
D-Ketose
Isomers

144
Under natural conditions, only one
enantiomer predominates – the D-isomer
cf. amino acid – L-isomer
e.g. monosaccharide – monosaccharide - = D-
monosaccharide

145
Diastereoisomer :
Diastereomers are stereoisomers that are not
enantiomers or mirror images of each other.
Diastereomers can have different physical
properties and different reactivity.

146
147
 Chiral carbons

Tetrose

Are they enantiomers?

148
149
 PENTOSE
Contains 5 carbon atoms
3 chiral carbons = 23
stereoisomers - 4 pairs of enantiomers - untuk
aldose = aldopentose
Stereochemistry of Longer
Monosaccharides
BUT ketopentose – only 2 chiral carbons
4
isomers only

150
Some D-
Aldose
Isomers

151
Aldopentose Ketopentose
152
 HEXOSE

● Monasaccharide with 6 carbon atoms

● Number of isomers – high
● Common hexosee = glucose & fructose,
● mannose & galactose also abundant – all
play important biological roles

153
154
 Cyclic Structures
Cyclic structures
• are the common form of monosaccharides with 5
or 6 carbon atoms.
O O

• form when the hydroxyl group on C-5 reacts with

the
– aldehyde group or
– ketone group.

155
 Drawing the Cyclic Structure for Glucose

STEP 1 : Number the carbon chain and turn clockwise to

form a linear open chain.

H O
1C H H OH H
O
2
H C OH HOCH 2 C C C C C
3 6 5 4 3 2 1 H
HO C H
4 OH OH H OH
H C OH
5
H C OH
6 CH
2OH
156
 H O
1C H H OH H
O
2
H C OH HOCH 2 C C C C C
3 6 5 4 3 2 1 H
HO C H
4 OH OH H OH
H C OH
5
H C OH
6 CH
2OH

157
 Drawing the Cyclic Structure for Glucose

STEP 2: Fold into a hexagon.

• Bond the C5 –O– to C1. 6
CH2OH
• Place the C6 group above the
ring. 5 O
• Write the –OH groups on C2 4 1
and C4 below the ring. OH
OH OH
• Write the –OH group on C3 3 2
above the ring. OH
• Write a new –OH on C1.

158
Drawing the Cyclic Structure for Glucose
STEP 3 : Write the new –OH on C1
• down for the α form.
• up for the β form.
CH2OH CH2OH β
O O
OH

OH
OH OH OH
OH
α
OH
OH
α-D-Glucose β-D-Glucose
159
Summary of the Formation of Cyclic Glucose

160
α-D-Glucose and β-D-Glucose in
Solution
When placed in solution,
• cyclic structures open and close.
• α-D-glucose converts to β-D-glucose and vice versa.
• at any time, only a small amount of open chain forms.
CH2OH CH2OH CH2OH
H
O O O
OH
O
OH C
OH OH
H OH
OH OH OH

OH OH OH
α-D-glucose D-glucose (open) β-D-glucose
(36%) (trace) (64%)

161
 Cyclic Structure of Fructose
Fructose
• is a ketohexose.
• forms a cyclic structure.
• reacts the —OH on C-5 with the C=O on C-2.
CH2OH
CH2OH CH2OH CH2OH OH
C O O O
HO C H OH OH
H C OH OH CH2OH
H C OH OH OH
CH2OH
D-fructose α--D-fructose β-D-fructose

162
 CYCLICAL STRUCTURE
CHO with 5 & 6 carbon atoms normally exist as ring
structures
Cyclization = interactions between functional groups at
● C-1 & C-5 hemiacetal (in aldohexose)
● Or between C-2 dan C-5 hemiketal (in ketohexose)
 carbonyl carbon becomes new chiral centre =
anomeric carbon

Cyclic sugars – 2 different forms - α dan β = Anomers

163
164
Hemiacetal &
Hemiketal

165
Drawing the Cyclic Structure for Glucose
New Chiral centre

Glucose
166
Drawing the Cyclic Structure for Fructose
New Chiral centre
1

2
6
3
2
5
4

5 4 3 1

Fructose
167
168
169
170
 CYCLICAL STRUCTURES
● CHO 5 carbon = furanose – furan
● CHO 6 carbon = pyranose – Pyran
● Normally CHO > 5 carbon – in cyclic form

o Free carbonyl group can form α @ β anomer

o Can change from one form to another
171
172
173
Furanose

174
pyranose

175
Which isomer used for reaction?
● Certain reactions – any isomer
● Others – only one anomer
eg. RNA & DNA – requires α-D-ribose & β -
D-deoksiribose
• Fischer Projection – usefull to explain
`stereochemsitry’ sugars,
But does not give true picture of overall shape
accurately.
∴ use HAWORTH PROJECTION FORMULA
176
 Haworth Projection
Formula
Fischer Projection α or β?
Formula
177
178
179
Important Simple Monosaccharides

1. Glucose
2. Mannose
3. Galactose
4. Fructose
5. Ribose

180
RNA - only ribofuranose
Dinding sel (polysaccharide) - pyranose

KETOPENTOSE – almost all in cyclic form, but

only furanose eg. a -D-ribulose

181
182
REACTIONS OF MONOSACCHARIDES

1. Mutarotation.
2. Oxidation to CO2 + H2O
Reactions due to aldehyde group
3. Reducing sugars.
4. Reduction to polyols.
Reactions due to alcohol group
5. Esterification.
6. Formation of acetals, also called glycosides

183
184
REACTIONS OF MONOSACCHARIDES
1. Oxidation & Reduction
● Important in biochemistry – provides energy
when CHO completely oxidised
● Photosynthesis – reversible process – when
CO2 & H2O reduced
● Oxidation reaction can be used to detect the
presence of carbohydrates
eg. Aldehyde [O]
carboxyl – basis for test for
aldose
When aldehyde is oxidised, the oxidising agent
is reduced
185
Because of his property, they are called reducing
agents.
Ketose is also a reducing agent – Y?
Ketoses can also be reducing sugars because they
can isomerise (a tautomerisation) to aldoses via an
enediol:

186
 REDUCING SUGARS

● Sugars that contain aldehyde groups that are

oxidised to carboxylic acids are classified as reducing
sugars.
● They are classified as reducing sugars since they
reduce the Cu2+ to Cu+ which forms as a red
precipitate, copper (I) oxide.

187
● Common test reagents are :

Benedicts reagent (CuSO4 / citrate)

Fehlings reagent (CuSO4 / tartrate)
hemi-acetal
● Remember that aldehydes (and hence aldoses) are
readily oxidised
● In order for oxidation to occur, the cyclic form must
first ring-open to give the reactive aldehyde (?)
● So any sugar that contains a hemi-acetal will be a
reducing sugar.
● But glycosides which are acetals are not reducing
sugars.

188
189
Another example of reagent for
reducing sugars – Tollen’s Reagent

Use silver ammonium complex Ag

(NH3)2+ as oxidising agent
mirror
precipitate on the walls of test
tube

RCHO + 2Ag(NH3)2+ + OH-

RCOO- + 2 Ag+ + 3NH3 + NH4+ + H2O

Other methods – use enzyme – glucose oxidase –

to detect glucose
190
 ESTERIFICATION REACTION

● Hydroxyl group (OH) in CHO reacts with acids

ester
● E.g. Phosphate ester – intermediate in the
breakdown of CHO
energy
● Phosphate ester is normally formed when the
phosphate from ATP reacts with sugars

phosphorylated sugar – important in the
metabolism of CHO

191
 MONASACCHARIDE DERIVATIVES
Monosaccharides have several OH groups – can
bind/exchange with other groups
modify the original
structures

A. Phosphate esters
Phosphate esters – found in many metabolsic pathways
- ATP, ADP, etc

B. Acid & lactones

Oxidation of monosaccharides produces
1. Aldonic acids – e.g. aldose reacting with alkaline
solution of Cu+
2. Lactone & uronic acids - [O] with enzim
192
Mannose

193
194
C. Alditols
Reduction of C=O


polyhydroxy compounds = eg D-
mannitol & D-glucitol

Ribitol or Adonitol is a crystalline

pentose alcohol (C5H12O5) formed
by the reduction of ribose. It
occurs naturally in the plant
Adonis vernalis

195
196
● Mannitol or 1,2,3,4,5,6-hexanehexol (C6H8(OH)6)
is a vasodilator which is used mainly to reduce
pressure in the cranium,

● Chemically, mannitol is an alcohol and a sugar,

or a polyol; it is similar to xylitol or sorbitol.

● Mannitol is also used as a sweetener for people

with diabetes.

197
198
D. Amino sugars
● 2 derivatives of amino sugars – in
polysaccharides – glucosamine &
galactosamine
● Exchange of OH with NH2

199
200
E. Glycoside
● glycosides are certain molecules in which a
sugar part is bound to some other part
● Bond = glycosidic bond
● Formed when H2O is removed from OH – of
saccharide & other compounds containing
OH-
● Found in plants/animals
● e.g. - Salicin, a glycoside related to Aspirin
NB: OH- must be attached to anomeric carbon
201
Salicin, a glycoside
related to Aspirin

202
203
● OH- from sugar with another OH-
ether
bond
● OH- - must be anomeric
● bond= glycosidic bond
● product = glycoside
furanose = furanoside, pyranose = pyranoside.

204
 OLIGOSACCHARIDES

 Glycosidic bonds between monosaccharides =

basis for the formation of oligosaccharides and
polysaccharides
 Bonds = between a anomer or b anomer and
another OH- of another sugar
  lots of combinations - OH- must be numbered
to differentiate
  notation for glycosidic bond – which
anomeric atom involved
e.g.. α(1 → 4), α(1 → 6), β (1 → 1)
205
206
 OLIGOSACCHARIDES

 Formed when two monosaccharides are

joined together by glycosidic bond
 Plays important roles in living organisms
 Simplest and most important oligosaccharide
= disaccharide
 Examples of disaccharide = sucrose, lactose,
maltose

207
4 important characteristics to differentiate
disaccharides
1. monomer found and their configuration

2. which carbon involved in the bond

3. the arrangement of the monomers

4. the anomeric configuration of the

hydroxyl group

208
Chemical characteristics of poly- &
oligosaccharides formed will depend on
1. Chemical characteristics of
monosaccahrides
2. The type of glycosidic bonds formed (i.e.
which anonmer; which carbon atom etc )
e.g. The differences between celluloses
and starch is because of the difference
in the glycosidic bond formed between
glucose
Because of the variation in the glycosidic bond,

can get various types of polymers – branched
or linear
209
210
211
Bond: β (1 → 4)

212
213
214
215
216
217
Example.
● Arrangement – starts with non-reducing end –left –
anomeric & enantiomeric – with prefixes
● Cyclic configuration with suffix
● Atoms between glycosidic bonds – the number
inside bracket between residues

Not all oligosaccharides are dimeric; also possible to

have trimers, tetramer and bigger

218
219
Sucrose -
● 2 Monosaccharides = α−D-Glucose & β-D- fructose
● Glucose = aldohexose = pyranose ; Fructosee =
ketohexose = furanose
● α-C-1glucose attached to fructose
● Not reducing sugar - why? – because both anomeric
groups are involved in glycosidic bond
● But free glucose and fructose are reducing sugars.
When sucrose is digested, hydrolysed  glucose &
frctose energy

220
221
Lactose

● A disaccharide formed from β-D- galactose & β-

D-glucose
● Galctose = epimer of glucose - ie. Reverse
position at C-4
● Glycosidic bond = β(1

4) between anomeric C-
1 ( β form) of galactose and C-4 carbon of
glucose

222
Because anomeric carbon of glucose is NOT
involved in the bond formation, can be in either α
&β

Lactose = reducing sugar because the groups at

the anomeric carbon atom (glucose) is not
involved in glycosidic bond formation; hence
can react with oxidising agents

223
224
 LACTOSE INTOLERANCE
Lactose= milk sugar

Human can be allergic to milk or milk products – why???

• lack of lactase (breaks lactose to galactose and glucose)

lactose will accumulate
• Lactose will be acted on by lactase bacteria
produce
Hydrogen gas, CO2 & organic acids – problems with
digestion – bloating and diarrhea
Although lactose can be degraded to galactose, galactose has
to be isomerised to glucose before being absorbed

can accumulate
GALACTOSEMIA – mental retardation

225
226
Maltose

 a disaccharide – hydrolytic product of starch

α-D-glucose & β-D-glucose
 2 molecules of D-glucose -α
joined by α(1
4) bond
 Different from celobiose
o hydrolysis of cellulose
o different glycosidic bond - D-glucose attached
through β(1
4)bond
o maltose can be digested by humans, cellobiose
cannot

227
228
Epimers are diastereomers that differ in configuration of
only one stereogenic center

Diastereomers are a class of stereoisomers that are non-

superposable, non-mirror images of one another

229
Epimers
230
 POLYSACCAHARIDE

 various functions
 sequence of monmer determines the primary
structure – normally simple monomers
● 1 type of monomer = homopolysaccharide
● 2 @ more = heteropolysaccharide
● normally not complex – not more than 2 residues
● Cf. Protein & nucleic acids - well defined length’ –
polysaccharide chain - random length -

231
 Storage Polysaccharide

1. Important examples - amylose & amylopectin - 

starch in plants and & glycogen in mammals and
bacterial cells
2. amylose, amylopectin & glycogen =
homopolysaccharide (glucan) - deposited in the
liver, otot

= polymer α-D-glucopyranose-
Difference – bond between residues

232
● amylose - linear, α(1
4)
● Amylopectin & glycogen α(1
4) + α(1
6),
branched polymer
● Glycogen - more branched; if not they are
very similar

233
234
• Regular and simple structure  regular secondary
structure
• α(1 4) bond , each residue leans slightly compared
to the previous resisue  helical conformation
• However, the helix is not stable- e.g. amylose form
random coils
• Iodine – can stabilise helix – because it can fit the
core of the helix
• Complex – blue in colour

235
236
Glycogen & amylopectin – cannot get blue colour
???

● Branches – inhibit formation of helix

● To form a helix – need 12 residue for ever
turn
● amylopectin - 10 -12 residues, glycogen - 8
residue – not enough

237
238
239
 STRUCTURAL POLYSACCHARIDE

Plants – do not use/synthesise structural protein

use specialIsed polysaccharide

animal – use both

Cellulose

 main polymer in plants - woody/fibrous

 Polymer linear - D-glucose ( glucan)
 4)bond
 Joined through β(1

240
241
• Animals- can digest starch – can cleave bond
• Cellulose - cannot – requires symbiotic bacteria -



produce enzyme cellulase
• Ruminant - OK- cellulase is present
• White ants – protozoa – can digest cellulse
• Fungi - eg. mushroom – live on rottting wood, etc
Other polysaccharides also found.
e.g.
 xylans = polymer β(1→ 4) - linked D-
xylopyranose
 Glucomanan = hemicellulose

242
● Cellulose – Not confined to plants only
● Marine Invetebrata - eg. Tunicates - cellulose in
the mantle
● in connective tissue - human

243
Tunicates
244
Tunicates 245
246
 CHITIN

• Similar to cellulose
• smalll difference - homopolymer N-asetil-D-
glucosamine - minor constituent in fungi and
algae- replace cellulose
• Role in invertebrate - exoskeleton of arthropod
& mollusks

247
248
249
250
 GLYCOSAMINOGLYCAN

In vertebrata - previously known as mucopolysacharide

● chondroitin sulphate
● keratan sulphate  connective tissue
● dermatan sulphate – skin
● Hyaluronic acid

1. All are polymers = repeating units of disaccharides

2. Sugar (CHO) = N-asetylgalactosamine @ N-
asetylglucosemine

251
252
253
Main functions of glycosaminoglycan

● formationn of matrix that bind protein components

with connective tissue eg. Proteoglycan – inside
cartilage - filemental structure synthesised from
hyaluronic acid with protein core
● Protein - keratin sulphate chain and chondroitin
sulphate chains are attached
Structure - collagen fibers becomes compact and strong
● Bonds – electrostatic between sulphate and basic
collagen side chains

254
255
Non Structural function of
glycosaminoglycan
Hyaluronic acid
● very soluble in water- found in-synovial
fluid- lubricating agent for joints
● vitreous humor – eyes – agent for increasing
fluidity
Heparin - anticoagulant – in body tissues – bound
strongly to blood proteins (prothrombin III) –
prevets enziymes in the coagulation of blood

256
Polysaccharides in bacterial cell walls
● Gram + & Gram – based on cell wall

● Gram + = peptidoglycan = polysaccharide –

peptide complex which are multilayered and
crosslinked

● Gram - = single layer of peptidoglycan covered

with membrane layer

257
Gram + bacteria
258
Gram - bacteria
259
Importance of other peptidoglycas
● A few antibiotics inhibit bacterial growth by
preventing peptidoglycan layers
● Lysozymes can dissolve cell walls
cell lysis

bacterial death
● Also found in bacteriophage, white of egg,
eyedrops of humans

260
 GLYCOPROTEIN
● Many proteins are bound to saccharide = glycoprotein
● Different functions
● Saccharide chain (= glycan) bound to protein -2 ways
◊ Bound to N of the amino group of asparagine - (N-
Iinked Glycans)
◊ Through
 N-acetylglycosmine @
 N-acetylgalactosamine

Differet structures – complex branched structures

Different functions – protein indicators – old proteins
that need to be destroyed
261
ABO blood group system, the classification of human
blood based on the inherited properties of
• red blood cells (erythrocytes) as determined by the
presence or absence of the antigens A and B, which
are carried on the surface of the red cells.
• These antigens may be proteins, carbohydrates,
glycoproteins, or glycolipids, depending on the blood
group system
• Persons may thus have type A, type B, type O, or
type AB blood

262
263
eg. immunoglobin – sialic acid residues will be cleaved
slowly, then receptor will recognise and bind to the
protein, engulf the protein

• O-linked Glycans

Different functions – e.g..

● Antartic fish – have glycoprotein which acts as

an “anti freez’ – fluids do not freeze although
temperature below freezing point
● Mucins - glycoprotein – in salive – increase
viscosity of fluid

264

Humans can produce antibodies against the A & B,
but NOT O; i.e. O is antigenic antigenic

Normally, antibodies react against other antigens.
eg. Type A carries antibodies against B - therefore
when receiving blood type B - will clot &
precipitate

Blood type O carries antibodies against A & B
∴cannot receive blood type A and B; but CAN
donate to both

Bllod Type AB – carries A & B antigens; therefore
no antibodies against A @ B ; only donatieto AB
only

265
 Oligosaccharides as CELL MARKERS

 Blood group antigens – a cell recognition phenomenon

 Cells need to be marked –(on the surface) so that they can
interact with other cells – can recognize own cells from
other external cells
 In animals – there a layer of saccharides bound to a protein
or lupid in the membranes – e.g. glycocalyx - can interact
with bacteria in the intestine; collagen
 To act as signal, need to have a specific protein bound
specifically - imunoglobulin
 Other examples – lectin – interact between cells and
proteins in the intercellulr matrix – to maintain the structure
of tissues and organs
266
267
Amino acid & Protein -1
 Amino acids and proteins
• Draw a general amino acid and identify the two functional
groups common to all.
• Classify each amino acid according to the chemical nature of
its R group.
• Define the meaning of an essential amino acid.
• Draw the reaction that joins two amino acids to form a
peptide bond.
• Describe and differentiate primary, secondary, tertiary, and
quaternary protein structures.
• Describe and differentiate co-enzymes and prosthetic
groups.
• List and discuss four forces that stabilize globular protein
structure.
 Proteins
Reverse
transcription Translation

DNA RNA protein

Transcription

Genotype Phenotype
Genome Proteome
(similar in all cells) (unique to all cells)
Amino Acid Structure

H Cα
+ -
H N C O
H
H O
Common Amino Acids in
Proteins
Common Amino Acids in
Proteins
 Amino Acid Non-Polar
R-groups Hydrophobi
c
Tryptophan
Polar Phenylalanine
Charged Uncharged Isoleucine
Arginine (+) Cysteine Tyrosine
Glutamic acid Proline Leucine
(-) Serine Valine
Ambivalent
Aspartic Acid Glutamine Methionine
Glycine
(-) Asparagine Threonine
Lysine (+) Alanine
Histidine (+)
 Hydrophobic Indexes
• Glycine Gly [G] 0
• Arginine Arg [R] -11.2 • Threonine Thr [T] 0.4
• Glutamic Acid Glu [E] -9.9 • Alanine Ala [A] 0.5
• Aspartic Acid Asp [D] -7.4
• Lysine Lys [K] -4.2 • Methionine Met [M] 1.3
• Histidine His [H] -3.3 • Valine Val [V] 1.5
• Cysteine Cys [C] -2.8 • Leucine Leu [L] 1.8
• Tyrosine Tyr [Y] 2.3
• Proline Pro [P] -0.5 • Isoleucine Ile [I] 2.5
• Serine Ser [S] -0.3 • Phenylalanine Phe [F] 2.5
• Glutamine Gln [Q] -0.3 • Tryptophan Trp [W] 3.4
• Asparagine Asn [N] -0.2
 Essential amino acids

• Definition - Those amino acids that cannot

be synthesized in the body in sufficient
quantities for anabolic needs.
• In humans,
Isoleucine Leucine Valine
Tryptophan Methionine
Lysine
Phenylalanine Threonine Histidine
Zwitterion Form of Amino Acids
H

+ C -
CO2
H3N
R
“zwitterion” = hybrid ion

form that exists at pH = 7

Recall from Acid-Base Equilibria:
Henderson-Hasselbalch Equation
-
[X ]
pH = pKa + log
[HX]
or
[base]
pH = pKa + log
[acid]
Amino acid & Protein -2
Recall: Amino Acids are Chiral*

*except glycine - R group is another H

 A zwitterion is formed when a proton (a
hydrogen nucleus) moves from the carboxylic
acid group to the amine group
-O O
H O O
C C
proto
+ R C H R C H
n, H ,
transf +
N H N H
ers to
H H
the
H
amin
e
group
The zwitterion ion forms when an amino acid is
dissolved in water – and this is how they are usually
found in nature
Alanine is an amino acid. Its molecular formula is C3H7O2N

Draw the structural formula for alanine. Click to see if you

got it right
Make a molecular model of alanine
H O O and use it to
C 1. investigate the shape of the
molecule and explain why can it
H 3C C H exist in two forms

N 2. show how its zwitterion is formed

H H Click to continue
Click
to
Look at the picture of the
continu
zwitterion.
e Replay Close window
1. where is the – NH + group?
 The shapes of some amino acid
molecules
O O
O
H3C
H2N OH HS OH
OH
NH2 NH2

glycin alanini cystei

e ne ne
Click for a useful website that allows you to compare the
shapes of amino acids
 Formation of the peptide bond

O O
Two amino acid molecules;
R1 R2 the nature of the R group (R1
OH OH and R2) determines the amino
NH2
acid
NH2

O
R2 The molecules must be
R1 orientated so that the
OH H2N carboxylic acid group of one
O can react with the amine group
NH2
of the other
HO

O
R2 The peptide bond forms with
R1 the elimination of a water
H2O
NH molecule;
molecule; it is another
O example of a condensation
NH2
reaction
HO
 Hydrolysis of the peptide bond

O
The peptide bond holds two R2
amino acid ‘residues’ together. R1
H2O
NH
It is a flat, rigid group
NH2 O
A water molecule reacts with
this group HO

O
The two amino acids form or, if
R2
the peptide bond is R1
somewhere in a long peptide OH H2N
chain, two smaller peptide O
NH2
molecules are formed
HO
 Bonding between peptide chains
Bonding within a peptide chain
(intramolecular) and between one chain and
another (intermolecular)
C O
Hydrogen bonds
These form in all proteins. The C O H N
hydrogen atom of the peptide
link is attracted to the oxygen of H N
another peptide link.

peptide chains
Covalent bonds
In a very small number of proteins, Ionic bonds
sulfur-
sulfur-sulfur covalent bonds (also If some of the amino acids in the
called cystine bonds or disulfide proteins have carboxylic acid or
bridges)
bridges) are present. amine side groups, an ionic bond
can form.
- CH2 – S – S – CH2 -
- COO- H 3N+ -
Amino acid & Protein -3
 Types of Proteins
Type Examples
• Structural tendons, cartilage, hair, nails
• Contractile muscles
• Transport hemoglobin
• Storage milk
• Hormonal insulin, growth hormone
• Enzyme catalyzes reactions in cells
• Protection immune response
314
 Amino Acids
• Building blocks of proteins
• Carboxylic acid group
• Amino group
• Side group R gives unique
characteristics

R side chain
I
H2H—C —COOH
I
H 315
 Examples of Amino Acids
H
I
H2N—C —COOH
I
H glycine
CH3
I
H2N—C —COOH
I
H alanine
316
 Types of Amino Acids
Nonpolar R = H, CH3, alkyl groups, aromatic
O
Polar ll
R = –CH2OH, –CH2SH, –CH2C–NH2,
(polar groups with –O-, -SH, -N-)
Polar/Acidic
R = –CH2COOH, or -COOH
Polar/ Basic
R = –CH2CH2NH2
317
 L-Form Amino Acid Structure

Carboxylic group -
COO
Amino group
+
H3 N α H

H = Glycine
R group
CH3 = Alanine
Juang RH (2004) BCbasics
Mirror Images of Amino Acid

α Mirror
image
α
Same chemical properties
Stereo isomers
Juang RH (2004) BCbasics
 Northwest line Chung-San line
-C-C-C-N-C-N Amino Acid Subway Map
Aromatic

=
N+
This is NOT a metabolic pathway
Basic Arg R Trp W -C-
N
-C- -OH Nan-Kan line
-C-CONH2 -C-C-CONH2
Lys K Tyr Y
+
Asn N Gln Q Amide
-C-C-C-C-NH3 -C-

-C-C C His H Phe F Asp D Glu E Acidic

N N+
-C-COOH -C-C-COOH
Aliphatic
Central line Gly G Ala A
A Val V Ile I Leu L
-H C C C C
-CH3
-C -C-C-C -C-C-C

Ser S Cys C

Juang RH (2004) BCbasics

-C-OH -C-SH C
Circular line C C
South line HN C-COOH
-C-C α
Non-polar Thr T Met M -C-C-S-C
Pro P
OH Imino,
Polar Hydroxy Sulfur Circular
 Classification of Amino Acids by Polarity

POLAR Acidic Neutral Basic

Asp Asn Ser Arg
Tyr Cys His
Glu Gln Thr Lys
Gly
POLAR

Ala Ile
NON-

Phe Trp
Val Leu Met Pro

Polar or non-polar, it is the bases of the amino acid properties.

Juang RH (2003) Biochemistry
 Formation of Peptide Bonds by Dehydration

Amino acids are connected head to tail

NH2 1 COOH NH2 2 COOH

Carbodiimide Dehydration
-H2O

O
NH2 1 C N 2 COOH
H
Juang RH (2004) BCbasics
 Peptide Bond Is Rigid and Planar

C H
C N
O C

Juang RH (2004) BCbasics

Protein Structure -4
 Proteins
Reverse
transcription Translation

DNA RNA protein

Transcription

Genotype Phenotype
Genome Proteome
(similar in all cells) (unique to all cells)
 Peptide bond formation

-
O O
H
Aspartate C Alanine
C C
H H H H
H Cα H Cα
+ + -
- H N
H N H C O H C O
H O H O
condensation
H2O
 Peptide bond formation
-
O O
C H
H H
C C
H H
H Cα H Cα
+ -
H N N H C O
H C
H O O
Peptide bond

Primary Structure
 Dipeptide
Peptide bond resonance
-
O O
C H
H H
C C
H H
H Cα H Cα
+ -
H N H C N H C O
+
H O- O
Peptide bond
 α-helixes

Intra-
chain
H-bonds

Secondary Structure
 β-strands

Inter-
chain
H-bonds

Secondary Structure
 Tertiary
Quaternary
structure
structure

Hb monomer Hb α2β2 tetramer

(or myoglobin)
 Protein Structure
Primary structure is the amino acid sequence.

Secondary structure is how the amino acids in

sequence fold up locally. Examples are α-
helixes and β-strands and loops.
Tertiary structure is the 3-dimensional folding of
the secondary structural elements and
connecting loops in space.

Quaternary structure is the association of

multiple subunits, each with a tertiary
structure and each a unique gene product.
 Stabilization of Protein
Structure
Electrostatic interactions involve the interaction
of (+) and (-) charged side groups.

Hydrogen bonds involve sharing of a hydrogen

atom between two eletronegative atoms (e.g.,
O, N).
Van der Waal’s forces are weak forces based on
optimal overlap of adjacent electronic
orbitals. Can be repulsive.

Hydrophobic interactions are, by far, the most

powerful force stabilizing protein structure.
Basis of force is entropy gain realized by
burying hydrophobic residues.
Hierarchy of Protein Structure

• 20 different amino acids: many combinations

Primary Structure
The order of amino acids: Protein sequence

Secondary Structure
Conformation varies depending on sequence

Tertiary Structure
Overall structure of the chain in full 3D
Give the name and structure
of at least 2 examples of
each of the following:
a. heterocyclic amino acid
b. aromatic amino acid
c. neutral amino acid
d. acidic amino acid
e. basic amino acid
f. sulfur containing amino
acid
 Secondary Structure
Local structure of consecutive amino acids
Common regular secondary structures
 α Helix
 β Sheet
 β turn
Amino acids have a greater propensity to form
some secondary structures versus others
 Chemical properties
 Spatial constraints
 Structure- α Helix
Secondary Structure-

H-bond
 Structure- β Sheet
Secondary Structure-

Oxygen Nitrogen Hydrogen

Carbonyl C Carbon α R Group
H Bond
 What Causes 2º, 3º, 4º
Structure?
• intermolecular forces
 peptide hydrogen bonds
 side-chain hydrogen bonds
 salt bridges
 London dispersion forces

• metal ion coordination

• disulfide bridges (covalent interaction)

Forces in Proteins
 Some Ways to Denature
Proteins
• heat
• pH changes
• chemical reagents
urea
urea
DMSO
HMPA
2-mercaptoethanol
Give the name and structure of
at least 2 examples of each of
the following:
a. heterocyclic amino acid
b. aromatic amino acid
c. neutral amino acid
d. acidic amino acid
e. basic amino acid
f. sulfur containing amino acid
Show me a chemical structure of a tripeptide
with 1 nonpolar,1 polar, and 1 charge amino
acids? Ensure that the charged amino acid
is at the C-terminal and the polar amino acid
is at the N-terminal.
1. How many peptide bonds are there
2. What are amino acids?
3. How many α-carbon can you find?
4. How many chiral centers?
5. In a solution of these oligopeptides, What sort
of interactions can develop?
Protein Structure - 5
Hierarchy of Protein Structure

• 20 different amino acids: many combinations

Primary Structure
The order of amino acids: Protein sequence

Secondary Structure
Conformation varies depending on sequence

Tertiary Structure
Overall structure of the chain in full 3D
 Protein Sequences
Amino terminus Carboxyl terminus
N C
Residue number 1 2 3 4

• 20 different amino acids: many combinations

A protein of n residues 20n possible sequences!

100 residue protein has 10020 possibilities 1.3 X 10130!
The latest estimates indicate on 40,000 sequences in
the human genome −> THERE MUST BE RULES!
 Protein Sequences
Amino terminus Carboxyl terminus
N C
Residue number 1 2 3 4

• 20 different amino acids: many combinations

A protein of n residues 20n possible sequences!

100 residue protein has 10020 possibilities 1.3 X 10130!
The latest estimates indicate on 40,000 sequences in
the human genome −> THERE MUST BE RULES!
 Protein Sequences
*Length is generally 100-1000 residues*
Minimum length for performing a function ~40
Molecular machines not perfect- errors
Function requires specific amino acid properties
 Not all amino acids are equally useful
 Abundant: Leu, Ala, Gly, Ser, Val, Glu
 Rare: Trp, Cys, Met, His
Post-translational modifications
 Addition of co-factors- metals, hemes
 Chemical modification- phosphate, glycos.
 Protein Sequences
The pattern of amino acid side chains determines
the secondary (and tertiary!!) structure
*Pattern is more important than exact sequence*

Reporting/Comparing Protein Sequences

h-CaM A T V R L L E W E D L
b-CaM A T V R L L E Y K D L
5 10

conservative non-conservative
 Secondary Structure
Local structure of consecutive amino acids
Common regular secondary structures
 α Helix
 β Sheet
 β turn
Amino acids have a greater propensity to form
some secondary structures versus others
 Chemical properties
 Spatial constraints
The Peptide Bond

Peptide plane is flat

ω angle ~180º

Partial double-bond:
H H

-
-
-C - N- -C = N-

=
O-

-
O
Peptide bond
Resonance structures
Βackbone Conformation

R H ψ
φ
Cα

Peptide planes

 ω angle is fixed, φ and ψ angles vary

Many φ/ψ
ψ combinations cause atoms to collide
 Βackbone Conformation
φ R H ψ
Cα

Cα Cα

H R H R

 Side chains collision also limit φ/ψ

ψ combinations
 Backbone restricted → Secondary structure limited
Specific Secondary Structures
Three acceptable backbone φ/ψ φ/ψ combinations
1. Right-hand helix: α-helix (-40°, -60°)
2. Extended: antiparallel β-sheet (140°, -140°)
3. Left-hand helix (rare
rare): α-helix (45°, 45°)
Glycine: special because it has no side chain!

Side chains positioned to minimize collisions →

amino acids prefer specific secondary structures

Hydrogen bonds between backbone atoms provide

unique stability to secondary structures
 Structure- β Sheet
Secondary Structure-

Oxygen Nitrogen Hydrogen

Carbonyl C Carbon α R Group
H Bond
 Structure- α Helix
Secondary Structure-

H-bond
 Structure- β Turn
Secondary Structure-

3 4

2 1

 Reverses direction of the chain

Titration of Amino Acids
-6
 Titration curves

Of amino acids and weak acids(acetic

acid)
 Titration
• Titration curves are produced by monitoring
the pH of given volume of a sample solution
after successive addition of acid or alkali
• The curves are usually plots of pH against the
volume of titrant added or more correctly
against the number of equivalents added per
mole of the sample
 Titration of acetic acid
• At the starting point the acid form predominates
(CH3COOH).
• As strong base is added (e.g. NaOH), the acid is
converted to its conjugate base.
• At the mid point of the titration, where pH=pK,
the concentrations of the acid and the conjugate
base are equal.
• At the end point(equivalence point), the
conjugate base predominates, and the total
amount of OH added is equivalent to the amount
of acid that was present in the starting point.
Titration
 Titration
Determination of pKa values:
pKa values can be obtained from the titration
data by the following methods:
1. The pH at the point of inflection is the pKa
value and this may be read directly
2. By definition the pKa value is equal to the pH
at which the acid is half titrated. The pKa can
therefore be obtained from the knowledge of
the end point of the titration.
 Titration of amino acids
• Titration of glycine
• Titration of arginine
 Titration

• When an amino acid is dissolved in water it

exists predominantly in the isoelectric form.
• Upon titration with acid, it acts as a base, and
upon titration with base, it acts as an acid( a
compound that can act as either an acid or a
base is known as an amphoteric compound).
• +H3N-CH2-COO- + HCl +H3N-CH2-COOH + Cl-
(base) (acid) (1)

+H N-CH -COO- + NaOH H2N-CH2-COO- + Na+ +H2O

3 2

(acid) (base) (2)

In this experiment, the amino acid represents
either the A- or the HA form in the
Henderson-Hasselbalch equation, depending
on the titration.
 Acid–base properties
• All of the amino acids have an acidic group
(COOH) and a basic group (NH2) attached to
the α carbon.
• Two of the amino acids have acidic side
chains: aspartate and glutamate.
• Three of the amino acids have basic side
chains: arginine, histidine, and lysine.
• All amino acids contain ionizable groups that
act as weak acids or bases, giving off or taking
on protons when the pH is altered.

These ionizations follow the Henderson-

Hasselbalch equation:
pH=pKa+log [unprotonated form(base)]
[protonated form (acid) ]
• When the conc of the unprotonated form
equals that of the unprotonated form, the
ratio of their concentrations equals 1, and log
1=0.
• Hence, pKa can be defined as the pH at which
the concentrations of the protonated and
unprotonated forms of a particular ionizable
species are equal.
• The pKa also equals the pH at which the
ionizable group is at its best buffering
capacity; that is the pH at which the solution
resists changes in pH most effectively.
• Consider applying the Henderson-Hasselbalch
equation to the titration of glycine with acid
and base.
• Glycine has two ionizable groups: a corboxyl
group and an amino group, with pKa values of
2.4 and 9.6 respectively.
• In water at pH 6, glycine exists as a dipolar ion,
or zwitterion, in which the carboxyl group is
unprotonated(-COO- ) and the amino group is
protonated to give the substituted ammonium
ion(-NH3+).
• Addition of acid to the solution lowers the pH
rapidly at first and then more slowly as the
buffering action of the carboxyl is exerted.
• At pH 2.4 the pKa is reached, one-half the acid
has been consumed, and the carboxyl group is
half ionized and is most effective as a buffer.
• Titration of the amino group with base follows a
similar curve into the alkaline region.
• The intersection between the titration of the
carboxyl group and the titration of the amino
group describes in this case the point at which
glycine has no net charge, and is called the
isoelectric point (pI).
 The isoelectric point (pI)
• the isoelectric point, pI, is the pH of an aqueous
solution of an amino acid at which the molecules
have no net charge. In other words, the positively
charged groups are exactly balanced by the
negatively charged groups.
• For simple amino acids such as alanine, the pI is
an average of the pKa's of the carboxyl (2.34) and
ammonium (9.69) groups. Thus, the pI for alanine
is calculated to be: (2.34 + 9.69)/2 = 6.02.
• If additional acidic or basic groups are present as
side-chain functions, the pI is the average of the
pKa's of the two most similar acids.
 Cont.. (pI)
• In the case of aspartic acid, the similar acids
are the alpha-carboxyl function (pKa = 2.1) and
the side-chain carboxyl function (pKa = 3.9), so
pI = (2.1 + 3.9)/2 = 3.0.
• For arginine, the similar acids are the
guanidinium species on the side-chain (pKa =
12.5) and the alpha-ammonium function (pKa
= 9.0), so the calculated pI = (12.5 + 9.0)/2 =
10.75.
• Most amino acids contain carboxyl and amino
groups having pKa values similar to those of
glycine.
• In addition to these groups, many amino acids
contain other ionizable groups, which
introduce other “steps” or pKa values into
their titration curves.
 Titration curves
• The pK is the pH at the midpoint of the buffering region
(where the pH changes only slightly upon addition of
either acid or base).
• The pK is the pH corresponding to the inflection point
in the titration curve.
• The end point of a titration curve represents the
observed end of the titration.
• The isoelectric point (isoelectric pH; pI) is the pH at
which the amino acid has a net zero charge. For a
simple diprotic amino acid, the pI falls halfway
between the two pK values. For acidic amino acids, the
pI is given by ½(pK1 + pK2) and for basic amino acids it’s
given by ½(pK2 + pK3)
Nucleic acids -1
Purines
Purine metabolism
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