CYP2A6: a human coumarin 7-hydroxylase.
Coumarin 7-hydroxylation is catalysed by a high-affinity CYP2A6 enzyme in human liver microsomes. CYP2A6 is the only enzyme catalysing this reaction and consequently the formation of 7-hydroxycoumarin can be used as 'an in vitro and in vivo probe' for CYP2A6. CYP2A6 is a major contributor to the oxidative metabolism of nicotine and cotinine, and it also contributes, to a larger or smaller extent, to the metabolism of a few pharmaceuticals (e.g. fadrozole), nitrosamines, other carcinogens (e.g. aflatoxin B1) and a number of coumarin-type alkaloids. CYP2A6 may be inducible by antiepileptic drugs and it is decreased in alcohol-induced severe liver cirrhosis. Several mutated or deleted CYP2A6 alleles have been characterized. Although CYP2A6 represent up to 15% of human microsomes P450 proteins, it is still one of the less well characterised cytochrome P450 enzymes.
Pelkonen
O
O
Department of Pharmacology and Toxicology, University of Oulu, PO Box 5000, FIN-90401, Oulu, Finland. olavi.pelkonen@oulu.fi
Rautio
A
A
Raunio
H
H
Pasanen
M
M
D000925:Anticoagulants / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases; D003374:Coumarins / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*
D000925:Anticoagulants; D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6