Simple Pharmanotes: Introduction to Enzymes.

Introduction:

Not destroyed during an enzyme action.
They can only speed up the reaction but can’t initiate the reaction.
Enzymes do not alter the equilibrium constant of a reaction but alter the rate at which equilibrium is reached.
A non enzymatic reaction may take several years to reach equilibrium, while an enzymatic reaction takes a fraction of a second.
Very specific. Their specificity is with regard to substrates and the reaction they catalyze.

All enzymes are proteins in nature (But all proteins are not enzymes)..
Many enzymes require the presence of other compounds such as cofactors, coenzymes and metal ions for their activity.
This entire active complex is referred to as the holoenzyme; i.e., apoenzyme (protein portion) plus the cofactor (coenzyme, prosthetic group or metal ion or activator).
Apoenzyme + Cofactor = Holoenzyme

A coenzyme - a substance which is thermo stable and loosely attached to the protein part.
A prosthetic group - an organic substance which is thermo stable and is firmly attached to the protein
A metal ion or activator – such as K+, Fe++, Fe+++, Cu++, Co++, Zn++, Mn++, Mg++, Ca++ etc.

One of the properties of enzymes that makes them so important as diagnostic and research tools is the specificity they exhibit relative to the reactions they catalyze.
A few enzymes exhibit absolute specificity; that is, they will catalyze only one particular reaction. Other enzymes will be specific for a particular type of chemical bond or functional group. In general, there are four distinct types of specificity:

Absolute specificity - The enzyme will catalyze only one reaction by acting on a single type of substrate . Eg: Glucokinase which converts only glucose to glucose 6- phosphate.
Group specificity - The enzyme will act on a group of related molecules. Eg : Hexokinase which acts on all hexoses and converts to their hexose phosphates.
Linkage specificity - The enzyme will act on a particular type of chemical bond regardless of the rest of the molecular structure. Eg: Proteases acting on various proteins.
Stereochemical specificity - The enzyme will act on a particular steric or optical isomer. Eg: L-Amino acid oxidases acting only on L- Amino acids.

It is part of an enzyme where substrates bind and undergo a chemical reaction.
The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that participate in recognition of the substrate.
Residues that directly participate in the catalytic reaction mechanism are called active site residues.

A chemical reaction such as A → P takes place because a certain fraction of the substrate possesses enough energy to attain an activated condition called the transition state.
The minimum energy required by the substrate to cross the energy barrier and thereby form products is called activation energy.
Every reactant has the required amount of energy but during the course of time some energy is lost when the reactants undergo collisions in the form of heat.
Hence enzymes decrease the activation energy so that more reactants cross the energy barrier and products are formed.
The transition state of the substrate is at the top of the energy barrier separating the reactants and products.
The rate of a given chemical reaction is proportional to the concentration of this transition state species.
The energy of activation is the amount of energy required to bring all the molecules in 1 mole of a substance at a given temperature to the transition state.
Enzymes combine transiently with the substrate to produce a transition state intermediate having a lower energy of activation than the uncatalysed reaction. Thus they accelerate chemical reactions by lowering the energy of activation.
Two theories were proposed to explain the mechanism of enzyme action,