Document Detail

Monomorphic and polymorphic isozymes of arylamine N-acetyltransferases in hamster liver: purification of the isozymes and genetic basis of N-acetylation polymorphism.
MedLine Citation:
PMID:  2265466     Owner:  NLM     Status:  MEDLINE    
Two forms of cytosolic acetyltransferases, AT-I and AT-II, have been purified from hamster livers, and a comparison made of their chemical and catalytic properties and genetically expressed difference. Homogeneous AT-I and AT-II were 31 and 30 kd respectively on SDS-PAGE and catalyzed efficiently various N- and O-acetylations in their reconstitution systems. AT-I used both acetyl CoA and arylhydroxamic acids as acetyl donors, while AT-II did not utilize arylhydroxamic acids as acetyl donors. In the reconstitution system, purified AT-I, but not AT-II, catalyzed acetyl CoA-dependent O-acetylation of 2-N-hydroxyamino-6-methyldipyrido[1,2-alpha:3', 2'-d]imidazole (N-OH-Glu-P-1) and arylhydroxamic acid-dependent N-acetylation of 4-aminoazobenzene (AAB). On the other hand purified AT-II showed high activities of acetyl CoA-dependent N-acetylation of 2-aminofluorene (AF) and p-aminobenzoic acid (PABA). Polyclonal antibodies raised against AT-I inhibited cytosolic acetylations of N-OH-Glu-P-1 and AAB, and to a lesser extent of AF, while PABA N-acetylation was only marginally inhibited. Using Western blots, both AT-I and AT-II were recognized by the antibodies. AT-I was detectable in all the livers examined, and the content did not differ among the individuals (monomorphic distribution). In contrast, AT-II was distributed polymorphically, and the trimodal distribution of AT-II (high, intermediate and low) was correlated with the phenotype identified by cytosolic N-acetylations of AF and PABA (rapid, intermediate and slow). In addition, cross-mating experiments with intra- and inter-phenotype animals confirmed that hepatic AT-II isozyme is inherited by a Mendelian co-dominant trait. These results indicate that the polymorphic appearance of an acetyltransferase, AT-II, is responsible for the N-acetylation polymorphism in individual hamsters.
S Ozawa; M Abu-Zeid; Y Kawakubo; S Toyama; Y Yamazoe; R Kato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  11     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1990 Dec 
Date Detail:
Created Date:  1991-02-12     Completed Date:  1991-02-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2137-44     Citation Subset:  IM    
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
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MeSH Terms
4-Aminobenzoic Acid
Acetyl Coenzyme A / pharmacology
Arylamine N-Acetyltransferase / analysis,  genetics*,  isolation & purification
Blotting, Western
Chromatography, Affinity
Chromatography, High Pressure Liquid
Electrophoresis, Polyacrylamide Gel
Fluorenes / metabolism
Imidazoles / metabolism
Isoenzymes* / isolation & purification
Liver / enzymology*
Polymorphism, Genetic*
p-Aminoazobenzene / metabolism
Reg. No./Substance:
0/Fluorenes; 0/Imidazoles; 0/Isoenzymes; 0/Mutagens; 150-13-0/4-Aminobenzoic Acid; 153-78-6/2-aminofluorene; 60-09-3/p-Aminoazobenzene; 72-89-9/Acetyl Coenzyme A; 73341-53-4/2-hydroxyamino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; EC N-Acetyltransferase

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