‘Hepatic microsomal enzymes’

Microsomal enzymes are typically found in the endoplasmic reticulum of

hepatocytes. Microsomes are fragments of endoplasmic reticulum and attached ribosomes that are
isolated together when homogenized cells are centrifuged.

The cytochrome P450 system is a group of enzymes that control the concentrations of many
endogenous substances and drugs. These enzymes are mainly found in the liver (hepatic
microsomal enzymes) and gut • Cytochrome P450 system is comprised of about 40- 50
isoenzymes. Each isoenzyme is derived from the expression of an individual gene. Originally the
system was identified as a pigment in hepatic microsomes.

When examined, the pigment had a characteristic spectrophotometric profile with an associated
peak at 450nm (hence the term cytochrome P450 system). The main effect of the cytochrome P450
enzymes is to catalyze oxidation, which generally makes the substrate more water-soluble and so
more readily excreted by the kidney. • There are many isoenzymes in the cytochrome P450 system,
only a few appear to be responsible for the metabolism of commonly used drugs (CYP 1A2, CYP
2C9, CYP 2C19, CYP 2D6, CYP 3A3, CYP 3A4).

The metabolism of drugs that are inactivated by the cytochrome P450 enzymes can be altered by
substances which either induce these enzymes and therefore increase degradation, or substances
that inhibit these enzymes and therefore are associated with increased levels of the drug CYP
enzymes have been identified in all domains of life - animals, plants, fungi, protists, bacteria,
archaea, and even in viruses

The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g.,
insertion of one atom of oxygen into the aliphatic position of an organic substrate (RH) while the
other oxygen atom is reduced to water: RH + O2 + NADPH + H+ → ROH + H2O + NADP.
+Human CYPs are primarily membrane-associated proteins located either in the inner membrane
of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolize thousands of
endogenous and exogenous chemicals.