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Biochemistry
Introduction
ƒBios = life - Greek
ƒal kimya = the transmutation - Arabic
ƒChemistry explains “change” using atoms.
ƒAll chemical change involves rearrangements of electrons.
ƒBiochemistry aims to explain biological form and function in
chemical terms. Biochemistry explains life in terms of atomic
structures of biological molecules.
ƒTo understand the biological phenomenon Î purify an individual
chemical component and characterize its chemical structure or
catalytic activity
ƒ What are the molecules present in a living organism, their
structures, chemical properties and how do they interact with
each other.
Chemical structure and bonding,
¾ Most of the elements in the living organism have relatively
low atomic number.
¾The four most abundant elements in the living organisms are
hydrogen, oxygen, nitrogen and carbon, which make up
together up to over 99% of the mass of most cells.
¾They are the lightest atoms capable of forming one, two,
three and four double bonds.
¾ Carbon make up 50% of dried cell mass.
¾Trace elements are also present, like Na, Ca, P, S...
they are essential to the function of specific protein, like
enzymes.
Biomolecules are compounds of carbon
The chemistry of organic compounds is
organized around carbon, which counts
for more than half of the dry weight of
cells.
Carbon can form
1. Single bonds with hydrogen,
2. Single and double bonds with oxygen
and nitrogen
3. Share pairs of electrons together to
form very stable carbon-carbon single
bonds.
4. Can form single, double and triple
bonds with another carbon
The four single covalent bonds are arranged tetrahedrally with an
angle of about 109.5 and its free in rotation unless a bulky group is on
one side
Covalently linked carbon atoms in biomolecules can form chains or
branched chains and cyclic structures. To these skeletons are added
groups of other atoms, called functional groups, which provide the
molecule with specific chemical properties.
Molecules with covalently bonded carbon backbones are called organic
compounds.
Most biomolecules are organic compounds.
Functional groups
¾Most biomolecules can be considered as derivatives of hydrocarbons.
¾ The backbones of hydrocarbons are very stable.
¾The hydrogen atom can be replaced by a variety of functional groups
to yield different families of organic compounds, e.g……….
¾Many biomolecules are polyfunctional, containing two or more
different functional groups, each with its own chemical characteristic
and reaction.
¾The chemical identity of a compound is determined by the chemistry
of its functional groups and their three dimensional arrangement.
Three dimensional arrangement (configuration and conformation)
¾ Not only is the functional groups of a biomolecules important for its
action, but also the three dimensional arrangement of the molecule is
important for its activity
¾ Compounds of carbon commonly exist as stereoisomers: molecules with
the same order of bonding but have different spatial relationship
among the atoms .
¾ Molecular interactions between biomolecules are mostly
stereospecific, that is, they require specific stereochemistry in
interacting molecules.
Configuration isomers
Configuration denotes the fixed spatial arrangement of atoms in an
organic molecule,
Configuration is determined by the presence of either
1) Double bonds, around which there is no freedom of rotation or
2) Chiral centers, around which subsistent groups are arranged in a
specific sequence.
The configuration can be only changed by breaking a bond.
Maleic acid (cis) and Fumaric acid (trans) have the same molecular
formula. Each is a well define chemical entity with its own chemical
properties. They have distinct biological roles despite their similar
chemistry
These isomers are called Geometric isomers
•A tetrahedral carbon with four
different substituents can be
arranged in two different ways
in space (have two configuration)
yielding two streoisomers with
identical chemical properties but
different in certain physical and
biological properties.
•A carbon atom with four
different subsituents is said to
be asymmetric and asymmetric
carbons are called chiral centers
•Number of sterreoisomers=2n,
where n is number of chiral
center.
• enantiomeres are mirror
images
Conformation isomers
Conformation refers to the spatial arrangement of substituent groups
that, without breaking any bonds, are free to assume different
positions in space because of freedom of bond rotation. It is not
possible to isolate these conformations because they are freely
interconvertible.
Configuration and conformation define biomolecular structures
¾The three-dimensional structure of biomolecules (small or large) which is a
combination of configuration and conformation is the most important for
their biological interaction.
¾Binding of a hormone to a receptor, substrate-enzyme interactions.
¾The three dimensional structure can be determined by certain
sophisticated techniques.
¾The interaction between biomolecules is streospecifc: in the living
organisms chiral molecules are usually present in one of their chiral forms.
For example amino acids are as the L isomer, glucose is always in the D
isomer. The interaction between biomolecules is stereospecific.
Chemical reactivity
The mechanisms of biochemical reactions are not different from those
of other chemical reactions.
Functional groups alter the electronic distribution and the geometry of
neighboring atoms and thus affect the chemical reactivity of the
entire molecule.
Most of the reactions that occur in living cells fall into one of the
following categories
a) Oxidation reactions
b) Cleavage and formation of carbon-carbon bonds
c) Internal rearrangement
d) Group transfer
e) Condensation reactions in which monomeric substituents are joined
together
Oxidation reduction reactions
•These are reactions that involve transfer of electrons from one atom to
another.
•In most biological oxidation, a molecule loses 2 electrons and 2 hydrogen ions
(2H), these reactions are called dehydrogenation Î dehydrogenases enzymes.
Oxidases and oxygenases add covalently O to carbon atom.
•Every oxidation must be coupled to a reduction, in which electron acceptor
acquires the electrons removed by oxidation.
•Oxidation usually releases energy. Most living cells obtain their energy needed
for cellular work by oxidizing metabolic fuels such as carbohydrates and fat.
•The electrons are
transferred from the fuel
molecules through a series
of electron carriers and
finally to oxygen, providing
the energy released to
synthesis ATP.
Carbon-Carbon bond cleavage
A covalent bond can be cleaved in two general ways;
¾ Homolytic cleavage: each atom leaves the bond as a radical and this
rarely occurs in living systems
¾ Heterolytic reactions: more common, in which one atom keeps both
bonding electrons (forming an anion) and the second one electron
short forming a cation.
When a second electron rich group replaces the departing anion, a
nucleophilic substitution occurs.
ƒMany biochemical reactions
involves interaction between
nucleophiles (functional groups
rich in electrons) and
electrophiles (electron deficient
functional groups that seek
electrons.
ƒ Functional groups containing
oxygen, nitrogen, and sulfur are
important biological nucleophiles.
ƒ Positively charged metals
frequently act as electrophiles
Mechanisms by which one
nucleophile replacement
Internal rearrangement
¾Another common cellular reaction is intramolecular rearrangement,
¾ redistribution of electron results in isomerization, transposition of
double bonds, and cis-trans rearrangement of double bonds.
¾An example of isomerization is the formation of fructose 6phosphate from glucose 6- phosphate during sugar metabolism (an
enzyme is involved isomerase).
Group transfer
¾Metabolic reaction usually involve attachment of a good leaving group to a
metabolic intermediate to activate this intermediate for subsequent
reaction
¾Among the better leaving groups in nucleophilic substitution reactions
are inorganic orthophosphate
Condensation
¾ Monomeric subunits form proteins, nucleic acids, and polysacharides.
¾These monomers are joined together by nucleopilic displacement
reactions that replace a good leaving group.
¾ For example: the joining of two amino acids to form a dipeptide could
occur by a simple mechanism.
¾Macromolecules can be broken
down by hydrolysis reactions, in
which H2O is the attacking
nucleophil, displacing a monomeric
subunit or a smaller polymer
fraction.
Macromolecules and their monomeric subunits
¾Many biological molecules are macromolecules; polymers of high
molecular weight assembled from relatively simple precursors.
¾ Polysaccharides, proteins and nucleic acids are produced by the
polymerization of relatively small compounds. The total number of units
can vary from ten to millions.
¾Synthesis of macromolecules is energy consuming.
¾Macromolecules themselves may further assemble to form
supramolecular complexes, forming functional units as ribosomes, which
are constructed from about 70 different proteins and different RNA
molecules.
¾These macromolecules are the major constituent of the cell
Major classes of biomolecules in cells
¾Water is the most abundant component.
¾Nearly all of the solid matter in cells is organic and is present in 4 forms
¾Proteins: long polymers of amino acids. Constitute the largest fraction of
cells. Some proteins have catalytic activity and function as enzymes.
Others are structural elements, signal receptors or transporters that
carry specific substances in and out of the cell.
¾Nucleic acids: DNA and RNA, are polymers of nucleotides. They store and
transfer the genetic information.
¾Polysaccharides: polymers of simple sugars such as glucose. Have two
functions: energy yielding stores and as extracellular structural elements.
Shorter polymers of sugar attached to proteins or lipids at the surface of
cells are involved as specific cell signals
¾Lipid: hydrocarbon derivatives. Serve as structural components of
membranes, energy-rich fuel stores, pigments, and intracellular signals.
¾Macromolecules are composed of monomeric subunits: although the
living organisms contain very large number of different nucleic acids and
proteins. The basic structure is very simple. The simple monomeric units
from which all proteins and nucleic acids are constructed are few in
number and identical in all living species.
¾Proteins and nucleic acids are informational macromolecules: each
protein and nucleic acid has characteristic information rich subunit
sequence.
¾Each of the basic subunits has multiple functions in living organisms.
¾Subunit condensation requires energy as creates a more ordered
state. It is extremely not probable that amino acids in a mixture would
condense simultaneously and form a protein. This would present a
greater degree of order .
¾The tendency in nature is toward ever greater disorder in the
universe. To bring about the synthesis of macromolecules from their
monomeric subunits free energy must be supplied to the system.
Structural hierarchy
The end