Cytochrome P450 Isozymes (CYP)- USMLE1

Cytochrome P450 Isozymes (CYP)

These are major enzyme systems involved in Phase I reactions. Localized in the smooth endoplasmic reticulum (microsomal fraction) of cells ( especially liver , but including GI tract, lungs ,and kidney)

·         P450s have an absolute requirement for molecular oxygen and NADPH.

·         Reactions include hydroxylation’s, oxidation,  and dealkylations.

·         Multiple CYP families differing by amino acid(AA) composition , by substrate specificity, and by sensitivity to inhibitors and to inducing agents.

Cytochrome P450 Isozymes:  3 types

• CYP1A
• CYP2D6

·         CYP3A4

CYP1A

·         Main substrate is theophylline; inhibited by fluoroquinolones and macrolides; induced by aromatic hydrocarbons.

CYP2D6

·         Genotypic variations in hydroxylation(fast and slow);substrates include codeine,and metaprolol; inhibited by haloperidol and quinidine; not inducible.

CYP3A4

·         Most abundant isoform; wide substrate range ; inhibited by cimetidine, macrolides, azoles, and ethanol(acute); induced by general P450 inducers such as carbamazepine, phenobarbital(Barbiturates), phenytoin, and rifampin and by ethanol(chronic).

Cytochrome P450 Isozymes:

·         These are major enzyme systems involved in Phase I reactions. Localized in the smooth endoplasmic reticulum (microsomal fraction) of cells (especially liver , but including GI tract, lungs ,and kidney)

·         Inhibited by : Cimitidine, Macrolides, Azoles (Miconazole, Ketoconazole), Alcohol (acute), grapefruit juice

·         Induced By : Carbamazepine, Barbiturate, Phenytoin, Rifampin, Alcohol (Chronic intake)