| N-acetylation pharmacogenetics. Michaelis-Menten constants for arylamine drugs as predictors of their N-acetylation rates in vivo. | |
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MedLine Citation:
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PMID: 2873982 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Michaelis-Menten constants for two in vivo monomorphically N-acetylated substrates, p-aminobenzoic acid and p-aminosalicylic acid, and two in vivo polymorphically N-acetylated substrates, sulfamethazine and procainamide, were determined with an improved assay procedure using liver N-acetyltransferase from rapid and slow acetylator rabbit. The slow rabbit liver isozyme proves to be a Vmax and a Km variant for p-aminobenzoic acid and p-aminosalicylic acid. Mean differences in the apparent Vmax for rapid acetylators were 39-fold greater for p-aminobenzoic acid and 16-fold greater for p-aminosalicylic acid. The apparent Km values for the slow acetylator enzyme were lower than 5 microM, whereas the apparent Km values for the rapid acetylator phenotype were at least 15 times higher, with a value of 105 +/- 21 microM for p-aminobenzoic acid and 74 +/- 16 microM for p-aminosalicylic acid. In contrast, for the polymorphic substrates, sulfamethazine and procainamide, rapid rabbit liver N-acetyltransferase was only a Vmax variant with a mean specific activity that was 13-fold higher than that for slow acetylator. |
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Authors:
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H H Andres; W W Weber |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 14 ISSN: 0090-9556 ISO Abbreviation: Drug Metab. Dispos. Publication Date: 1986 Jul-Aug |
Date Detail:
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Created Date: 1986-09-25 Completed Date: 1986-09-25 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 382-5 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Aminobenzoic Acid
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metabolism* Acetyl Coenzyme A / metabolism Acetyltransferases / genetics, metabolism* Aminobenzoic Acids / metabolism* Aminosalicylic Acid / metabolism* Aminosalicylic Acids / metabolism* Animals Kinetics Liver / enzymology Procainamide / metabolism* Rabbits Sulfamethazine / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GM-27028/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aminobenzoic Acids; 0/Aminosalicylic Acids; 150-13-0/4-Aminobenzoic Acid; 51-06-9/Procainamide; 57-68-1/Sulfamethazine; 65-49-6/Aminosalicylic Acid; 72-89-9/Acetyl Coenzyme A; EC 2.3.1.-/Acetyltransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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