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K Nagata, BM Martin, JR Gillette and HA Sasame
Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
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)
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