NH2-terminal sequence analyses of four rat hepatic microsomal cytochromes P-450 |
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Authors: | M Haniu D E Ryan S Iida C S Lieber W Levin J E Shively |
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Institution: | 3. Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010 U.S.A.;1. Department of Experimental Carcinogenesis and Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110 U.S.A.;2. Alcohol Research and Treatment Center, Bronx Veterans'' Administration Medical Center and Mt. Sinai School of Medicine, New York, New York 10468 U.S.A. |
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Abstract: | Cytochromes P-450f, P-450g, P-450h, and P-450i are four hepatic microsomal hemoproteins that have been purified from adult rats. Whereas cytochromes P-450g and P-450h appear to be male-specific hemoproteins, cytochrome P-450i is apparently a female-specific enzyme purified from untreated adult female rats. Cytochrome P-450f has been purified from adult male and female rats with equivalent recoveries. Amino-terminal sequence analyses of the first 15-20 amino acid residues of each of these cytochromes P-450 has been accomplished in the current investigation. Each protein possesses a hydrophobic leader sequence consisting of 65-87% hydrophobic amino acids, and only one charged amino acid (Asp) in the amino-terminal region. Although differences in the amino-terminal sequences of cytochromes P-450f, P-450g, P-450h, and P-450i are identified, these hemoproteins all begin with Met-Asp, and marked structural homology is observed among certain of these enzymes. Cytochromes P-450g and P-450h, two male-specific proteins, have 11-12/15 identical residues with cytochrome P-450i, a female-specific isozyme. Cytochromes P-450f and P-450h have 16/20 identical amino-terminal residues. Only limited sequence homology is observed between the amino-terminal sequences of cytochromes P-450f-i compared to rat liver cytochromes P-450a-e. The results demonstrate that cytochromes P-450f, P-450g, P-450h, and P-450i are isozymic to each other and five additional rat hepatic microsomal cytochrome P-450 isozymes (P-450a-e). |
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