Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10.
The cytochrome P-450 monooxygenase system possesses catalytic activity toward many exogenous compounds (e.g., drugs, insecticides, and polycyclic aromatic hydrocarbons) and endogenous compounds (e.g., steroids, fatty acids, and prostaglandins). Multiple forms of cytochrome P-450 with different substrate specificities have been isolated. In the present paper we report the isolation and sequence of a cDNA clone for the human hepatic cytochrome P-450 responsible for mephenytoin (an anticonvulsant) oxidation. The mephenytoin cytochrome P-450 is analogous to the rat cytochrome P-450 form termed PB-1 (family P450C2C). We also report that human PB-1 is encoded by one of a small family of related genes all of which map to human chromosome 10q24.1-10q24.3. The endogenous role of this enzyme appears to be in steroid oxidations. This cytochrome P-450 family does not correspond to any of the hepatic cytochrome P-450 gene families previously mapped in humans.
Meehan
R R
RR
Molecular Genetics Section, Western General Hospital, Edinburgh, Scotland.
Gosden
J R
JR
Rout
D
D
Hastie
N D
ND
Friedberg
T
T
Adesnik
M
M
Buckland
R
R
van Heyningen
V
V
Fletcher
J
J
Spurr
N K
NK
D000818:Animals; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D006801:Humans; D006822:Hybrid Cells; D007527:Isoenzymes / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008617:Mephenytoin / Q000378:metabolism; D051379:Mice; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D010084:Oxidation-Reduction; D010957:Plasmids; D051381:Rats; D013256:Steroids / Q000378:metabolism; D013379:Substrate Specificity
D007527:Isoenzymes; D013256:Steroids; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D004262:DNA Restriction Enzymes; D008617:Mephenytoin