J. Biol. Chem., Vol. 257, Issue 23, 13951-13957, Dec, 1982

Catalytic activity of cytochrome P-450 isozyme 3a isolated from liver microsomes of ethanol-treated rabbits. Oxidation of alcohols

ET Morgan, DR Koop and MJ Coon

Cytochrome P-450 isozyme 3a, isolated from hepatic microsomes of rabbits treated chronically with ethanol, was found to have a unique substrate specificity when compared with isozymes 2, 3b, 3c, and 4. Form 3a has unusually high activity in the p-hydroxylation of aniline and in the oxidation of alcohols to aldehydes. These properties are reflected in the increased activities of these substrates in microsomes from ethanol-treated rabbits as compared to microsomes from untreated animals or those administered phenobarbital or 5,6-benzoflavone. The ethanol-oxidizing activity of isozyme 3a, which requires the presence of NADPH and NADPH cytochrome P-450 reductase and is stimulated by the presence of phospholipid, was shown not to be due to contaminating catalase or an NAD- or NADP-dependent alcohol dehydrogenase. Isozyme 3a catalyzes the oxidation of methanol, 1-propanol, and 1-butanol as well as ethanol; the relationships between the apparent Km values for these alcohols and their octanol-water partition coefficients is in accord with the known hydrophobic nature of the P-450 binding site. Whereas typical substrates of isozyme 2 are known to be metabolized with the stoichiometry predicted of a monooxygenase reaction, with isozyme 3a the sum of acetaldehyde formed from ethanol and of hydrogen peroxide generated is inadequate to account for the NADPH and oxygen consumed. Free hydroxyl radicals appear to mediate the slow oxidation of ethanol in the presence of the reductase alone but not the faster rate catalyzed by P-450 isozyme 3a. The results obtained, however, do not rule out the involvement of hydroxyl radical equivalent generated and bound at the active site of the cytochrome.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. D. Porter JUD COON: 35 YEARS OF P450 RESEARCH, A SYNOPSIS OF P450 HISTORY Drug Metab. Dispos., January 1, 2004; 32(1): 1 - 6. [Abstract] [Full Text] [PDF]

				T. Matsunaga, H. Tanaka, S. Higuchi, K. Shibayama, N. Kishi, K. Watanabe, and I. Yamamoto Oxidation Mechanism of 7-Hydroxy-Delta 8-tetrahydrocannabinol and 8-Hydroxy-Delta 9-tetrahydrocannabinol to the Corresponding Ketones by CYP3A11 Drug Metab. Dispos., November 1, 2001; 29(11): 1485 - 1491. [Abstract] [Full Text] [PDF]

				P. Taavitsainen, R. Juvonen, and O. Pelkonen In Vitro Inhibition of Cytochrome P450 Enzymes in Human Liver Microsomes by a Potent CYP2A6 inhibitor, trans-2-Phenylcyclopropylamine (Tranylcypromine), and Its Nonamine Analog, Cyclopropylbenzene Drug Metab. Dispos., March 1, 2001; 29(3): 217 - 222. [Abstract] [Full Text]

				S. M. Lankford, S. A. Bai, and J. A. Goldstein Cloning of Canine Cytochrome P450 2E1 cDNA: Identification and Characterization of Two Variant Alleles Drug Metab. Dispos., August 1, 2000; 28(8): 981 - 986. [Abstract] [Full Text]

				K. Kobayashi, M. Nakajima, K. Oshima, N. Shimada, T. Yokoi, and K. Chiba Involvement of CYP2E1 as A Low-Affinity Enzyme in Phenacetin O-Deethylation in Human Liver Microsomes Drug Metab. Dispos., August 1, 1999; 27(8): 860 - 865. [Abstract] [Full Text]

				T. Matsunaga, N. Kishi, H. Tanaka, K. Watanabe, H. Yoshimura, and I. Yamamoto Major Cytochrome P450 Enzyme Responsible for Oxidation of Secondary Alcohols to the Corresponding Ketones in Mouse Hepatic Microsomes. Oxidation of 7-Hydroxy-Delta 8-tetrahydrocannabinol to 7-Oxo-Delta 8-tetrahydrocannabinol Drug Metab. Dispos., October 1, 1998; 26(10): 1045 - 1047. [Abstract] [Full Text]

				L. D. Gruenke, K. Konopka, M. Cadieu, and L. Waskell The Stoichiometry of the Cytochrome P-450-catalyzed Metabolism of Methoxyflurane and Benzphetamine in the Presence and Absence of Cytochrome b(5) J. Biol. Chem., October 20, 1995; 270(42): 24707 - 24718. [Abstract] [Full Text] [PDF]