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.