Microheterogeneity of a male-specific rat hepatic cytochrome P-450: existence of three allozymic forms |
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| Authors: | A Rampersaud D J Waxman D E Ryan W Levin F G Walz |
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| Affiliation: | 1. Department of Chemistry, Kent State University, Kent, Ohio 44242 USA;2. Department of Biological Chemistry and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 USA;3. Laboratory of Experimental Carcinogenesis and Metabolism, Roche Institute of Molecular Biology, Nutley, New Jersey 07110 USA;1. Drug Metabolism & Pharmacokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, Japan;2. Laboratory Animal Research Department and Technical Service Department, Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan;3. Technical Service Department, Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan;4. Showa Pharmaceutical University, Machida, Tokyo, Japan;1. Laboratory Animal Research Department, Japan;2. Pathology Analysis Center, Japan;3. ICLAS Monitoring Center, Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan;4. ADME & Tox. Research Institute, Sekisui Medical Co., Ltd., 3-13-5 Nihombashi, Chuo-ku, Tokyo, 103-0027, Japan;5. Chromosome Engineering Research Center (CERC), Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503, Japan;6. Division of Genome and Cellular Functions, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan;7. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machidashi, Tokyo, 194-8543, Japan;8. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan;1. Central Institute for Experimental Animals, Kawasaki, Japan;2. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Japan |
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| Abstract: | Preparations of hepatic cytochrome P-450 h [D. E. Ryan, et al. (1984) J. Biol. Chem. 259, 1239] and cytochrome P-450 2c [D. J. Waxman (1984) J. Biol. Chem. 259, 15481] from outbred Sprague-Dawley rats were analyzed using two-dimensional electrophoresis and in situ peptide mapping. Both preparations consisted of the same isozyme which was previously characterized as a developmentally regulated, male-specific cytochrome P-450 active in the 16 alpha-hydroxylation of steroids. Each preparation evidenced microheterogeneity which was shown, in part, to result from the existence of two genetically determined variant forms of cytochrome P-450 h/2c. Analyses of hepatic microsomes from several inbred strains of rat revealed that each was characterized by a single variant form of this isozyme, with some strains expressing a variant that was not present in Sprague-Dawley rats. Genetic crosses indicated that these electrophoretic variants represent allozymic forms of cytochrome P-450 h/2c which are codominantly expressed at a single autosomal locus. Additional microheterogeneity of each allozymic form of cytochrome P-450 h/2c was shown to result from a specific in vitro modification that may involve limited proteolysis near its C terminus by a microsome-bound protease. |
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