Biochemistry

IntroductionBios = life - Greek

al kimya = the transmutation - Arabic

Chemistry explains “change” using atoms.

All chemical change involves rearrangements of electrons.

Biochemistry aims to explain biological form and function in chemical terms. Biochemistry explains life in terms of atomic structures of biological molecules.

To understand the biological phenomenon purify an individual chemical component and characterize its chemical structure or catalytic activity

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,Most of the elements in the living organism have relatively

low atomic number. The 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.

They are the lightest atoms capable of forming one, two, three and four double bonds.

Carbon make up 50% of dried cell mass.Trace elements are also present, like Na, Ca, P, S...

they are essential to the function of specific protein, like enzymes.

Biomolecules are compounds of carbonThe 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 nitrogen3. 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 sideCovalently 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 groupsMost biomolecules can be considered as derivatives of hydrocarbons.The backbones of hydrocarbons are very stable.

The hydrogen atom can be replaced by a variety of functional groups to yield different families of organic compounds, e.g……….

Many biomolecules are polyfunctional, containing two or more different functional groups, each with its own chemical characteristic and reaction.

The 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)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 Compounds of carbon commonly exist as stereoisomers: molecules with the same order of bonding but have different spatial relationship among the atoms .Molecular interactions between biomolecules are mostly

stereospecific, that is, they require specific stereochemistry in interacting molecules.

Configuration isomersConfiguration 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 or2) 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 chemistryThese 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 chiralcenter.• enantiomeres are mirror images

Conformation isomersConformation 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 structuresThe three-dimensional structure of biomolecules (small or large) which is a

combination of configuration and conformation is the most important for their biological interaction.

Binding of a hormone to a receptor, substrate-enzyme interactions.The three dimensional structure can be determined by certain

sophisticated techniques.The 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 reactivityThe 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 theentire molecule.

Most of the reactions that occur in living cells fall into one of the following categories

a) Oxidation reactionsb) Cleavage and formation of carbon-carbon bondsc) Internal rearrangementd) Group transfere) 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 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 cleavageA covalent bond can be cleaved in two general ways;

Homolytic cleavage: each atom leaves the bond as a radical and this rarely occurs in living systems

Heterolytic reactions: more common, in which one atom keeps both bonding electrons (forming an anion) and the second one electronshort forming a cation. When a second electron rich group replaces the departing anion, a nucleophilic substitution occurs.

Many biochemical reactions involves interaction between nucleophiles (functional groups rich in electrons) and electrophiles (electron deficient functional groups that seek electrons.

Functional groups containing oxygen, nitrogen, and sulfur are important biological nucleophiles.

Positively charged metals frequently act as electrophiles

Mechanisms by which one nucleophile replacement

Internal rearrangementAnother common cellular reaction is intramolecular rearrangement, redistribution of electron results in isomerization, transposition of

double bonds, and cis-trans rearrangement of double bonds.An example of isomerization is the formation of fructose 6-

phosphate from glucose 6- phosphate during sugar metabolism (an enzyme is involved isomerase).

Group transferMetabolic reaction usually involve attachment of a good leaving group to a

metabolic intermediate to activate this intermediate for subsequent reaction

Among the better leaving groups in nucleophilic substitution reactions are inorganic orthophosphate

Macromolecules can be broken down by hydrolysis reactions, in which H2O is the attacking nucleophil, displacing a monomeric subunit or a smaller polymer fraction.

CondensationMonomeric subunits form proteins, nucleic acids, and polysacharides.

These monomers are joined together by nucleopilic displacement reactions that replace a good leaving group.

For example: the joining of two amino acids to form a dipeptide could occur by a simple mechanism.

Macromolecules and their monomeric subunitsMany biological molecules are macromolecules; polymers of high

molecular weight assembled from relatively simple precursors.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.

Synthesis of macromolecules is energy consuming.Macromolecules 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.

These macromolecules are the major constituent of the cell

Major classes of biomolecules in cellsWater is the most abundant component.Nearly all of the solid matter in cells is organic and is present in 4 formsProteins: 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.

Nucleic acids: DNA and RNA, are polymers of nucleotides. They store and transfer the genetic information.

Polysaccharides: 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

Lipid: hydrocarbon derivatives. Serve as structural components of membranes, energy-rich fuel stores, pigments, and intracellular signals.

Macromolecules 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.

Proteins and nucleic acids are informational macromolecules: each protein and nucleic acid has characteristic information rich subunit sequence.

Each of the basic subunits has multiple functions in living organisms.Subunit 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 agreater degree of order .

The 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