| Pyruvate dehydrogenase complex-catalyzed formation of N-arylacetohydroxamic acids from nitroso aromatic compounds in rat isolated cells and perfused organs. | |
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MedLine Citation:
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PMID: 8968352 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The formation of N-arylacetohydroxamic acid derivatives from m-nitrosobenzyl alcohol (MBNO) and a nitroso derivative of chloramphenicol, 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrosophenyl) ethyl]acetamide, in the presence of pyruvate was investigated with rat isolated cells (heart, kidney, liver, small intestine, lung, bone marrow and spermatozoa) and perfused organs (liver and heart). The activity in N-(m-hydroxymethylphenyl) acetohydroxamic acid (MBHA) formation was found in all the cells tested. Measurement of the kinetic parameters revealed that K(m) values of MBNO were ca. 0.3 mM and that the order of Vmax per cell was heart > kidney > liver > small intestine. In the hepatocytes, MBHA was metabolized further and the in vitro intrinsic clearance of MBHA was 1.91 +/- 0.24 ml/min/10(8) cells. In a single-pass perfusion of rat liver with MBNO, the corresponding amino, acetylamino and azoxy derivatives and unknown materials were formed in addition to MBHA. The activity in MBHA formation was increased by the addition of both diethyl maleate and paraoxon. In a recirculating perfusion of rat liver with MBNO, however, the net MBHA formation was hardly detected, because of the disposition of MBHA formed. The hepatic clearance of MBHA was 1.15 +/- 0.06 ml/min/g of liver. In a recirculating perfusion of isolated rat heart with MBNO, MBHA was formed as a major metabolite and further biotransformation was not found. The N-arylacetohydroxamic acid derivative of 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrosophenyl) ethyl]acetamide was also formed in rat bone marrow cells and the isolated perfused heart. These results indicate that the formation of N-arylacetohydroxamic acids from nitroso aromatic compounds and pyruvate catalyzed by pyruvate dehydrogenase complex proceeds in virtually all mammalian tissues. |
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Authors:
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T Yoshioka; H Ohno; T Uematsu |
Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 279 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1996 Dec |
Date Detail:
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Created Date: 1997-01-23 Completed Date: 1997-01-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1282-9 Citation Subset: IM |
Affiliation:
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Department of Chemical Hygiene, Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Catalysis Cells, Cultured Hydroxamic Acids / chemistry, metabolism* Liver / cytology, metabolism Male Maleates / pharmacology Nitroso Compounds / metabolism* Pyruvate Dehydrogenase Complex / metabolism* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Hydroxamic Acids; 0/Maleates; 0/Nitroso Compounds; 0/Pyruvate Dehydrogenase Complex; 141-05-9/diethyl maleate; 546-88-3/acetohydroxamic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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