Cytochrome P450 (CYP Enzymes)

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Cytochrome P450 (CYP Enzymes)

Oxidative reactions account for the majority of the phase I metabolic reactions. The predominant enzymes that catalyze phase I reactions are the oxygenase enzymes of the cytochrome P450 family. We will focus most of our discussion of phase I drug metabolism on cytochrome P450, or CYP enzymes (as they have come to be called).
Cytochrome P450 consists of a superfamily of proteins containing a heme cofactor. When the heme iron is reduced by forming an adduct with CO, the enzyme absorbs light at 450 nm. CYP enzymes catalyze the conversion of a wide range of substrates, from the endogenous steroids and cholesterol to xenobiotics. Xenobiotics are any substances, including drug molecules, that are foreign to the body.
CYP enzymes are classified according to the similarities in the amino acid sequences of the particular gene they are derived from.
CYP Families
  • Members of each family are derived from genes that have 40% of their amino acid sequence structure in common.
  • There are at least 74 CYP families, but only seventeen have been identified in humans.
  • Families are named by adding a number to CYP. Example: CYP1, CYP2, CYP3
CYP Subfamilies
  • Members of each subfamily are derived from genes that have 55% of their amino acid sequence structure in common.
  • About thirty subfamilies have been identified in humans.
  • Subfamilies are named by adding a letter to the CYP family. Example: CYP1A, CYP2D, CYP3A
Individual CYP Isoform
  • Each isoform is a variant derived from one specific gene.
  • There are about fifty genes that are important in humans.
  • Each isoform is named by adding a number to the CYP subfamily. Example: CYP1A2, CYP2D6, CYP3A4