How Enzymes Action Can Be Inhibited ? Inhibition Types !! Biological Sciencess !!!

Enzyme action Inhibition

(a) denaturation of enzymes
(b) competitive inhibition
(c) non competitive inhibition
(d) allosteric modification of feedback inhibition

(a) Denaturation

Change in the spatial arrangement of polypeptide chain within the protein molecule so that its unique structure is changed. As a result, the physical or biological properties are changed.

(b) Reversible Inhibition

1. Competitive inhibition

A substance which closely resembles actual
substrate structure competes with the substrate for the active site. There is a decline in the number of actual substrate molecule binding the site, as many of these are occupied by closely resembling substance. As a result, enzyme action is inhibited. Can be reversed by increasing the substrate concentration. Vmax unaffected & Apparent Km increased by factor (1 + [I]) /KI).

Examples:
• Inhibition of activity of succinate dehydrogenase by malonate & oxaloacetate.
• Sulpha drugs e.g. sulphanilamide inhibit the synthesis of folic acid in bacteria by competing with p-amino benzoic acid (PABA).
• AZT and AIDS
• Methotrexate and dihydrofolate reductase

2. Non competitive inhibition

The inhibitor has no structural similarity
to the substrate and forms an enzyme-inhibitor complex at a point other
than its active site so that the globular structure of the enzyme is changed.
As a result, even if the substrate is able to bind with the enzyme, catalysis cannot take place. It is characteristic of allosteric and multisubstrate enzymes. Km unaffected in simplest case. Vmax decreased by factor (1
+ [I])/KI) Cyanide inhibits the activity of cytochrome oxidase. Di isopropyl
fluorophosphates (nerve gas) effects nerve impulse transfer by combining
irreversibly with amino acid serine of acetylcholine esterase. It also poisons a number of other enzymes with trypsin, chymotrypsin, phsphoglucomutase,
elastase etc. Iodo acetamide inhibits enzymes having sulphahydrol or
imidazole group.

3. Uncompetitive

(I binds to ES complex). Km, Vmax both decrease.

Characteristic of multisubstrate enzymes

(c) Irreversible inhibitors

Generally achieved by Covalent modification. Similar to non-competitive kinetics (Vmax lowered, Km unaffected) Examples:
(i) PCMB and GAPDH
(ii) DFP and Serine hydrolases (trypsin, chymotrypsin, acetyl choline esterase,
etc)
(iii) Suicide substrates: generation of reactive intermediate by enzyme

(d) Feedback inhibition

The product of an enzyme catalysed reaction/chain of reactions accumulates and acts as inhibitor of the reaction. e.g. Inhibition of threonine deaminase by isoleucine. Proteases are added in detergents and amylase is used for dish washing.

• Trypsin is added to partially predigested food. Immobilisation of enzymes is done by attaching or trapping enzymes in inert supporting materials for better efficiency and recovering them after the reaction.

• Alloenzymes are enzymes which are produced by different genes.

• Constitutive enzymes are always present because they are always required for vital process e.g. glycolysis.

• Repressible enzymes – normally remain present but are repressed when a specific chemical or product is present e.g. glucokinase.

• Inducible enzymes – are formed in response to presence of its substrate
e.g. lactose.

• ELISA – It is an enzyme linked immunosorbentassay when a protein,
antibody or antigen is detected by means of a specific enzyme e.g. AIDS.

• Restiction endonuclease – These are enzymes which are used to break DNA at a specific site producing sticky ends. The enzymes are highly important for genetic engineering. Arber, Nathans and Smith were awarded Nobel Prize in 1978 for their discovery.

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