Isozymes of cytochrome P-450 that metabolize naphthalene in liver and lung of untreated mice.
Four isozymes, designated P-450m50a, P-450m50b, P-450m51a, and P-450m51b, have been isolated from liver microsomes of untreated male CD-1 mice. Electrophoretograms revealed that the molecular weights of P-450m51a and P-450m51b were about 51,000, whereas those of P-450m50a and P-450m50b were about 49,700 and 49,500, respectively. The present study is concerned mainly with the elucidation of the characteristics of P-450m50b and P-450m51a, since they appear to be major forms of cytochrome P-450 in mouse liver. End group analyses have revealed that these forms differ not only from P1-450, isolated previously from mouse liver, but also from any other known isozymes of cytochrome P-450. Naphthalene was metabolized by both P-450m50b and P-450m51a, but the turnover number of P-450m50b was 2-4 times greater than that of P-450m51a. Moreover, P-450m50b formed predominantly (1R,2S)-naphthalene 1,2-oxide, as determined by the formation of trans-1(R)-hydroxy-2(R)-glutathionyl-1,2-dihydronaphthalene, whereas P-450m51a formed both (1R,2S)- and (1S,2R)-naphthalene 1,2-oxide in about equal amounts. Although cytochrome P-450c, isolated from rat liver, is also known to convert naphthalene predominantly to (1R,2S)-naphthalene 1,-2-oxide, an antibody prepared against cytochrome P-450c failed to inhibit the formation of the glutathione conjugate when the 1R,2S-oxide was formed by either pure P-450m50b or by microsomes from mouse lung. Thus, P-450m50b probably is not orthologous to cytochrome P-450c.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagata
K
K
Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Martin
B M
BM
Gillette
J R
JR
Sasame
H A
HA
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009281:Naphthalenes / Q000378:metabolism*; D010449:Peptide Mapping; D013379:Substrate Specificity
D007527:Isoenzymes; D009281:Naphthalenes; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione