HOW INHIBITORS HELP TO CONTROL METABOLISM?
Many metabolic pathways are self-controlling. When a substance is needed, a particular pathway is activated to produce it. When enough has been produced, the pathway is deactivated.
This happens because some enzymes in a metabolic pathway are inhibited by the end product. When the product is once more in short supply, the inhibition is lifted and the pathway becomes active again. This self-regulation is an example of negative feedback. This is a fundamental principle of homeostasis.
An inhibitor is a chemical substance which can react (in place of substrate) with the enzyme but is not transformed into product(s) and thus blocks the active site temporarily or permanently (for example poisons, like cyanide, antibiotics, antimetabolites and some drugs).
Enzyme inhibitors are molecules that interact in some way with the enzyme to prevent it from working in the normal manner.
Inhibitors may be nonspecific or specific. Specific inhibitors may be irreversible or reversible (competitive and noncompetitive).
A nonspecific inhibition affects all enzymes in the same way. Non-specific methods of inhibition include any physical or chemical changes which ultimately denature the protein portion of the enzyme. Two main types are:
Usually, the reaction rate increases with temperature, but with enzyme reactions, a point is reached when the reaction rate decreases with increasing temperature. At high temperatures the protein part of the enzyme begins to denature, thus inhibiting the reaction.
(ii) Acids and Bases:
Enzyme activity is also controlled by pH. As the pH is decreased or increased, the nature of the various acid and amine groups on side chains is altered with resulting changes in the shape or structure of the enzyme.
Specific inhibitors may be irreversible or reversible (competitive and noncompetitive).
These form strong covalent bonds with an enzyme.
These inhibitors may act at, near, or remote from the active site.
They may not be displaced by the addition of excess substrate.
The basic structure of the enzyme is modified to the degree that it ceases to work.
Since many enzymes contain sulfhydral (-SH), alcohol, or acid groups as part of their active sites, any chemical which can react with them acts as an irreversible inhibitor. Heavy metals such as Ag+, Hg2+, Pb2+ have strong affinities for -SH groups.
They form weak linkages with the enzyme. Their effect can be neutralized completely or partly by increase in the substrate concentration.
They are of two types which are competitive and non-competitive.
(i) Competitive Inhibitors:
They have structural similarity with the substrate and are selected by the binding sites. They cannot activate the catalytic sites. As a result product(s) are not formed. Substrate
(ii) Non-Competitive Inhibitors:
They form enzyme inhibitor complex at a point other than the active site. They change the enzyme structure in such a way that even if a substrate binds the active site, catalysis do not occurs.