Slide 26 of 76
Notes:
- The cytochromeP450 system is a superfamily of microsomal heme-containing enzymes which chemically oxidize or reduce drugs and endogenous substances such as steroid hormones, fatty acids, and prostaglandins. The P450 term is derived from:
- initial beliefs that these enzymes were thought to be similar to mitochondrial cytochromes
- they are red in colour (pigment)
- they maximally absorb light at 450 nm wavelength under certain conditions
- Classified into families, subfamilies, and individual enzymes
- Families: all members have ᡠ% identity in amino acid sequences (indicated by a number)
- Subfamilies: amino acid sequences are ᡯ% identical (indicated by letter)
- Individual enzymes within a subfamily (indicated by number)
- Approximately 30 P450 families have been identified in humans
- Of these, only 3 families (CYP1, CYP2, CYP3) are currently thought to be responsible for the majority of hepatic drug metabolism.
- CYP450 enzymes are present in high concentrations in the liver; they are also present in lower concentrations in other areas of the body, including the gastrointestinal tract, kidneys, lungs, and brain.
- The presence and amount of certain CYP isozymes may also vary between individuals
(i.e., genetic polymorphism), and may also be affected by HIV status [Kashuba et al. ICAAC 2000, abstract #1169]
