| 内容提要: |
Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a heme cofactor and, therefore, are hemoproteins 5. The name of P450 is derived from the unusual spectral properties of the complex between reduced CYP and CO, which is characterized by a pronounced peak at 450 nm 6. In the human liver they are the most important enzymes in the phase 1 metabolism of drugs and xenobiotics 7, but some human CYPs are expressed in other tissues and metabolize endogenous compounds. Human CYPs are membrane bound enzymes that are either located on the cytoplasmic side of the endoplasmic reticulum or on the matrix side of the inner mitochondrial membrane; in general, they are the terminal oxidases of short electron transfer chains that consist of the CYP enzyme proper together with one or two electron transfer proteins that are colocalized with them; most human CYPs depend on NADPH-cytochrome P450 oxidoreductase (POR or CPR) 8. Such CYP systems can catalyze a variety of reactions, such as hydroxylation, N-, O- and S-dealkylation, sulfoxidation, epoxidation, deamination, dehalogenation, peroxidation, and N-oxide reduction 6; in this way they contribute to the transformation of lipophilic drugs into more hydrophilic drug metabolites 7.
In humans, most of the human CYPs, e.g. CYP1A2, CYP2B6, CYP2A6, CYP2C8, CYP2C9, CYP19, CYP2E1, CYP2D6, and CYP3A4, are primarily located in the liver and have been studied intensively due to their importance in drug metabolism9. By contrast, the research on CYPs in extrahepatic organs is much more limited. |