Identification of P-450ALC in microsomes from alcohol dehydrogenase-deficient deermice: Contribution to ethanol elimination in vivo
dc.contributor.author | Handler, Jeffrey A. | en_US |
dc.contributor.author | Koop, Dennis R. | en_US |
dc.contributor.author | Coon, Minor J. | en_US |
dc.contributor.author | Takei, Yoshiyuki | en_US |
dc.contributor.author | Thurman, Ronald G. | en_US |
dc.date.accessioned | 2006-04-07T20:16:25Z | |
dc.date.available | 2006-04-07T20:16:25Z | |
dc.date.issued | 1988-07 | en_US |
dc.identifier.citation | Handler, Jeffrey A., Koop, Dennis R., Coon, Minor J., Takei, Yoshiyuki, Thurman, Ronald G. (1988/07)."Identification of P-450ALC in microsomes from alcohol dehydrogenase-deficient deermice: Contribution to ethanol elimination in vivo." Archives of Biochemistry and Biophysics 264(1): 114-124. <http://hdl.handle.net/2027.42/27237> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6WB5-4DPC64B-20W/2/442f321d562268b48585f381c90283fc | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/27237 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=3395117&dopt=citation | en_US |
dc.description.abstract | Isozyme 3a of rabbit hepatic cytochrome P-450, also termed P-450ALC, was previously isolated and characterized and was shown to be induced 3- to 5-fold by exposure to ethanol. In the present study, antibody against rabbit P-450ALC was used to identify a homologous protein in alcohol dehydrogenase-negative (ADH-) and -positive (ADH+) deermice, Peromyscus maniculatus. The antibody reacts with a single protein having an apparent molecular weight of 52,000 on immunoblots of hepatic microsomes from untreated and ethanol-treated deermice from both strains. The level of the homologous protein was about 2-fold greater in microsomes from naive ADH- than from naive ADH+ animals. Ethanol treatment induced the protein about 3-fold in the ADH+ strain and about 4-fold in the ADH- strain. The antibody to rabbit P-450ALC inhibited the microsomal metabolism of ethanol and aniline. The homologous protein, termed deermouse P-450ALC, catalyzed from 70 to 80% of the oxidation of ethanol and about 90% of the hydroxylation of aniline by microsomes from both strains after ethanol treatment. The antibody-inhibited portion of the microsomal activities, which are attributable to the P-450ALC homolog, increased about 3-fold upon ethanol treatment in the ADH+ strain and about 4-fold in the ADH- strain, in excellent agreement with the results from immunoblots. The total microsomal P-450 content and the rate of ethanol oxidation were induced 1.4-fold and 2.2-fold, respectively, by ethanol in the ADH+ strain and 1.9-fold and 3.3-fold, respectively, in the ADH- strain. Thus, the total microsomal P-450 content and ethanol oxidation underestimate the induction of the P-450ALC homolog in both strains. A comparison of the rates of microsomal ethanol oxidation in vitro with rates of ethanol elimination in vivo indicates that deermouse P-450ALC could account optimally for 3 and 8% of total ethanol elimination in naive ADH+ and ADH- strains, respectively. After chronic ethanol treatment, P-450ALC could account maximally for 8% of the total ethanol elimination in the ADH+ strain and 22% in the ADH- strain. Further, cytochrome P-450ALC appears to be responsible for about one-half of the increase in the rate of ethanol elimination in vivo after chronic treatment with ethanol. These results indicate that the contribution of P-450ALC to ethanol oxidation in the deermouse is relatively small. Desferrioxamine had no effect on rates of ethanol uptake by perfused livers from ADH-negative deermice, indicating that ethanol oxidation by a hydroxyl radical-mediated mechanism was not involved in ethanol metabolism in this mutant. Peroxisomal [beta]-oxidation capacity was increased 40% over control values by ethanol treatment, consistent with the hypothesis that the increase in ethanol elimination in the ADH-negative deermouse is mediated predominantly via catalase-H2O2. | en_US |
dc.format.extent | 1378496 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Identification of P-450ALC in microsomes from alcohol dehydrogenase-deficient deermice: Contribution to ethanol elimination in vivo | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbsecondlevel | Chemical Engineering | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Biological Chemistry, Medical School, The University of Michigan, Ann Arbor, Michigan 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Department of Biological Chemistry, Medical School, The University of Michigan, Ann Arbor, Michigan 48109, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, U.S.A. | en_US |
dc.identifier.pmid | 3395117 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/27237/1/0000244.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0003-9861(88)90576-0 | en_US |
dc.identifier.source | Archives of Biochemistry and Biophysics | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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