Revision:Introductory Biochemistry

Macromolecules

Contents 1 Macromolecules 1.1 Amino Acids 1.2 Enzymes 1.2.1 Introduction 1.2.2 Active site 1.2.3 Classification of enzymes 1.2.4 Cofactors 1.2.5 Catalysts 1.2.6 Factors affecting enzymic activity 1.2.7 Measuring enzymic activity 1.2.8 Enzyme inhibitors 1.2.9 Examples of enzyme inhibition in drugs 1.3 Nucleic Acids

Amino Acids

An amino acid is a molecule containing both amine and carboxyl functional groups. They are the building blocks of proteins. They have the following general structure.

The carboxyl group (-COOH) and the amino group (-NH₂) can be ionised and unionised. Hence the amino acid can adopt a Non-Ionized, Ionized from and a Zwitterion form (Zwitter coming from the German word for "hybrid".)

There are 20 different amino acids which make up proteins. Their side chains can be separated into 3 groups:

1. Non-Polar (E.g Glycine, Alanine etc.)
2. Polar. (E.g Serine, Cysteine)
3. Charged. (E.g Aspartic Acid, Lysine)

These side chains have different reactivities and disulphide bonds between Cystine amino acids provide common bonds in proteins. Amino acids are also joind together by Peptide bonds.

There are two degrees of freedom around each residue of the peptide chain. These are termed Phi (φ) and Psi (Ψ). Phi is the angle about NH to C_α. Psi is the angle at C_α to C=O. Free rotation can occur at 180° in these bonds.

Enzymes

Introduction

An enzyme is a biomolecule that increase the rate of a chemical reaction. Most enzymes are proteins. But they can also be made of RNA (Ribozymes) or be RNA-Protein complexes (Ribosome). They often catalyse reactions with cofactors and coenzymes. Enzymes work by reducing the activation energy barrier, without affecting the overally change in free energy.

Active site

The 3D structure of the protein is critical for its function. Catalysis occurs in a specific site of the enzyme, called the active site. The side chains of the amino acids in the proteins associate with this active site by making and breaking bonds. Active site binding involves many weak, non-covalent ineractions (Electrostatics, Hydrogen bonding, Van der waals forces and hydrophobic interactions). These side chains are called Catalytic groups.

Classification of enzymes

No.	Class	Type of reaction catalyzed
1	Oxidoreductases	Transfer of electrons (Hydride ions or hydrogen atoms).
2	Transferases	Group transfer reactions
3	Hydrolases	Hydrolysis reactions (Transfer of functional groups to H2O)
4	Lyases	Addition of groups to double bonds, or formation of double bonds by removal of groups.
5	Isomerases	Transfer of groups within molecules to yield isomeric forms.
6	Ligases	Formation of C-C, C-S, C-O and C-N bonds by condensation reaction coupled to ATP cleavage.

Cofactors

A cofactor is a non-protein chemical compound that is bound (either tightly or loosely) to a protein and is required for the protein's biological activity. Cofactors are also often further classified depending on how tightly they bind to the protein, with loosely-bound cofactors termed coenzymes(E.g NAD, NADP⁺) and tightly-bound cofactors termed prosthetic groups (E.g FAD, Metal ions).

Catalysts

The four criteria for a catalyst are:

1. Bold textCatalysts increase he rate of reaction.
2. Catalysts are not consumed by the reaction.
3. A smal quantity of catalyst should be able to affect the rate of reaction for a large amount of reactant.
4. Catalysts do not chand the equilibrium constant for reactions.

Examples of catalysts include FeCl₃(An inorganic catalyst) which can increase the conversion of Hydrogen Peroxide to water and oxygen by about a 1000x and Catalase (A biological catalyst) which increase the reaction rate by about a 1,000,000x.

Factors affecting enzymic activity

pH

pH affects the degree to which the substrate is ionized. This alters the binding of the enzyme to the substrate. Extreme pHs can denature enzymes.

Temperature

Most enzymic driven reactons increase in rate, when temperature is increased. A temperature of about 40° usually denatures enzymes.

Measuring enzymic activity

Enzymic activity can be measured in a unit called a Katal (Kat). 1 Kat is equalt to the activity which transforms 1 mole of substrate per second under standard conditons.

Enzyme inhibitors

Enzyme inhibitors can be divided into four groups.

1. Irreversible inhibitors - Form of break covalent bonds with or in the enzyme. May be substrate analogues. Effect cannot be reversed by increasing substrate cocnentration.

1. Reversible inhibitors - Interact with the enzyme via non-covalent interactions. Effect can be reversed by increasing substrate concentration.

1. Competitive inhibitors - Inhibitor binds only to enzyme, not enzyme-substrate complex.

1. Noncompetitive inhibitor - Inhibitor binds either to enzyme and/or to Enzyme-Substrate complex.

Examples of enzyme inhibition in drugs

Penicillin - Inhibits enzymes responsible for the construction of the bacterial cell wall.

Sulfa drugs (E.g Sulfanilamide) - Inhibits the first enzyme in the metabolic pathway that bacteria use to make folic acid (Vitamin B9.)

Nucleic Acids