Feedback Inhibition of Enzymes | Biochemistry

Learn about:- 1. Meaning of Feedback Inhibition 2. Control of Enzyme Synthesis –Induction 3. Control of Enzyme Synthesis –Repression and De-repression.

Meaning of Feedback Inhibition:

The changes in the concentration of substrates, coenzymes, activators or inhibitors affect the cata­lytic efficiency of an enzyme. Feedback inhibition inhibits the activity of an enzyme early in the biosynthetic pathway.

In the biosynthetic reaction, sequences leading from A to D is catalysed by en­zymes Enz₁ through Enz₃:

A high concentration of D will inhibit con­version of A to B. D is specifically able to bind to and inhibit Enz₁. D thus acts as a negative allos­teric effector or feedback inhibitor of Enz₁. This feedback inhibition on an early enzyme by an end product of its own biosynthesis achieves regula­tion of synthesis of D.

Frequently the feedback inhibitor is the last small molecule before a macromolecule, e.g, amino acid before proteins or nucleotides before nucleic acid.

Feedback inhibition is a mechanism for regu­lation of many bacterial and mammalian enzymes, e.g., dietary cholesterol restricts the synthesis of cho­lesterol from acetate in mammalian tissues. The feedback regulation is not involved in feedback inhibition of an early enzyme of cholesterol bio­synthesis.

An early enzyme (HMG-CoA reductase) is affected, but the mechanism involves curtailment by cholesterol or a cholesterol metabolite of the expression of the gene that code for the formation of HMG-CoA reductase (i.e. enzyme repression). The catalytic activity of HMG-CoA reductase is not effected by the direct addition of cholesterol.

The kinetics of feedback inhibition may be competitive, non-competitive, mixed etc. It is the common path of regulation of a biosynthetic path­way.

In cumulative feedback inhibition, the inhibi­tory effect of two or more end products on a single regulatory enzyme is strictly additive.

Complete inhibition occurs only when two or more end prod­ucts are present in excess in multivalent feedback inhibition.

In cooperative feedback inhibition, a single end product present in excess inhibits the regulatory enzyme.

Control of Enzyme Synthesis –Induction:

For a molecule to be metabolized or for an inducer to act, it first must enter the cell. In some cases, a specific transport system or permease is needed. Permeases have many properties in com­mon with enzymes and perform functions like cytochromes in electron transport.

Escherichia coli grown on glucose will not ferment lactose due to the absence of specific permeases for a β-galactoside (Lactose) and of β-galactosidase. If lactose is added to the medium, both the permease and the β-galactosidases are in­duced and the culture will now ferment lactose.

The inducer (lactose) is a substrate for the induced proteins, the permease and the β-galactosidase. Enzymes whose concentration in a cell is in­dependent of an added inducer are termed consti­tutive enzymes.

The structural genes which specify a group of catabolic enzymes comprise an operon. All the en­zymes of that operon are induced by a single in­ducer. This process is known as coordinate induc­tion.

Control of Enzyme Synthesis –Repression and De-repression:

In bacteria, the presence of the synthesized particular amino acid in the culture medium pre­vents new synthesis of that amino acid via repres­sion. A small molecule such as histidine or leucine, acting as a co-repressor, can ultimately block the synthesis of the enzymes involved in its own syn­thesis.

The genetic information coding for the bio­synthesis of enzymes is again expressed after the removal or exhaustion of an essential biosynthetic intermediate from the medium. This is termed as de-repression.