Document Detail


N-acetylation pharmacogenetics. Michaelis-Menten constants for arylamine drugs as predictors of their N-acetylation rates in vivo.
MedLine Citation:
PMID:  2873982     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H H Andres; W W Weber
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  1986-09-25     Completed Date:  1986-09-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  382-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
4-Aminobenzoic Acid / 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:
GM-27028/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
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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