Enzyme induction and inhibition

From Wikipedia, the free encyclopedia

Enzyme induction is a process in which a molecule (e.g. a drug) induces (i.e. initiates or enhances) the expression of an enzyme.

Enzyme inhibition can refer to

• the inhibition of the expression of the enzyme by another molecule
• interference at the enzyme-level, basically with how the enzyme works. This can be competitive inhibition, uncompetitive inhibition, non-competitive inhibition or partially competitive inhibition.

If the molecule induces enzymes that are responsible for its own metabolism, this is called auto-induction (or auto-inhibition if there is inhibition). These processes are particular forms of gene expression regulation.

These terms are of particular interest to pharmacology, and more specifically to drug metabolism and drug interactions. They also apply to molecular biology.

[edit] Cytochrome P450

One class of key enzymes for drug metabolism belong to the family of cytochrome P450 oxidases, like CYP3A4, CYP2D6, CYP1A2, etc. They reside in the endoplasmatic reticulum (ER), and prolonged usage of substances inducing enzymes here may cause proliferation of the ER. They are responsible for phase I reactions.

Enzyme induction and inhibition are important processes to take in account when using drugs of vital importance to the patient, drugs with important side effects and drugs with small therapeutic windows, but any drug may be subject to an altered plasma concentration due to altered drug metabolism.

A classical example includes anti-epileptic drugs. Phenytoin, for example, induces CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Substrates for the latter may be drugs with critical dosage, like amiodarone or carbamazepine, whose blood plasma concentration may decrease because of enzyme induction.

Not only drugs may alter drug metabolism. Cigarette smoke induces CYP1A2 (example substrates are clozapine/olanzapine), Saint-John's wort (a common herbal remedy) induces CYP3A4, which is inhibited by grapefruit juice. There are known examples of situations where this may produce clinical effects.