Linked Life Data

2253236

Source:http://linkedlifedata.com/resource/pubmed/id/2253236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
1991-1-23
pubmed:abstractText
The polymorphic acetyltransferase isozyme expressed in homozygous rapid acetylator inbred hamster liver cytosol was purified over 2000-fold by sequential Q-Sepharose fast-flow anion-exchange chromatography, Sephacryl S-200 high-resolution size-exclusion chromatography, Mono Q anion-exchange fast-protein liquid chromatography, and preparative polyacrylamide gel electrophoresis. The isozyme migrated as a single homogeneous monomer following both preparative and sodium dodecyl sulfate-polyacrylamide electrophoresis. The molecular weight was estimated at 34,170 following elution via size-exclusion chromatography and 35,467 following migration via sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The homogeneous polymorphic acetyltransferase exhibited a broad substrate specificity; it catalyzed the acetyl coenzyme A-dependent N-acetylation of p-aminobenzoic acid, carbocyclic arylamine carcinogens such as 2-aminofluorene, 4-aminobiphenyl and beta-naphthylamine, and heterocyclic arylamine carcinogens such as 2-aminodipyrido[1,2-a:3'2'd]imidazole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole. It also readily catalyzed the acetyl coenzyme A-dependent metabolic activation (via O-acetylation) of N-hydroxy-2-aminofluorene to DNA adducts but not the metabolic activation (via intramolecular, N,O-acetyltransfer) of N-hydroxy-2-acetylaminofluorene or N-hydroxy-4-acetylaminobiphenyl to DNA adducts. Conversely, the partially purified monomorphic acetyltransferase isozyme from the same hamsters readily catalyzed the metabolic activation of N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl, and rates of metabolic activation of these substrates did not differ between homozygous rapid and slow acetylator liver, intestine, kidney, and lung cytosols. Heat inactivation rates for the purified polymorphic acetyltransferase isozyme were first order and indistinguishable for the acetyl coenzyme A-dependent N-acetylation and O-acetylation activities. The results strongly suggest the expression of a single polymorphic acetyltransferase product of the hamster polymorphic acetyltransferase gene that catalyzes both acetyl coenzyme A-dependent N-acetylation and O-acetylation of arylamine and N-hydroxyarylamine carcinogens but not the metabolic activation of N-hydroxy-N-acetylarylamines (arylhydroxamic acids) via intramolecular N,O-acetyltransfer. Consequently, acetylator genotype-dependent metabolic activation of N-hydroxyarylamines to a DNA adduct in hamster is catalyzed by direct O-acetylation of the hydroxyl group and not via sequential N-acetylation followed by N,O-acetyltransfer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7942-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:2253236-Acetyltransferases, pubmed-meshheading:2253236-Acyltransferases, pubmed-meshheading:2253236-Animals, pubmed-meshheading:2253236-Arylamine N-Acetyltransferase, pubmed-meshheading:2253236-Chromatography, Gel, pubmed-meshheading:2253236-Chromatography, Ion Exchange, pubmed-meshheading:2253236-Cricetinae, pubmed-meshheading:2253236-Cytosol, pubmed-meshheading:2253236-DNA, pubmed-meshheading:2253236-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:2253236-Genotype, pubmed-meshheading:2253236-Homozygote, pubmed-meshheading:2253236-Intestines, pubmed-meshheading:2253236-Kidney, pubmed-meshheading:2253236-Kinetics, pubmed-meshheading:2253236-Liver, pubmed-meshheading:2253236-Lung, pubmed-meshheading:2253236-Male, pubmed-meshheading:2253236-Mesocricetus, pubmed-meshheading:2253236-Molecular Weight, pubmed-meshheading:2253236-Polymorphism, Genetic
pubmed:year
1990
pubmed:articleTitle
Purification of hepatic polymorphic arylamine N-acetyltransferase from homozygous rapid acetylator inbred hamster: identity with polymorphic N-hydroxyarylamine-O-acetyltransferase.
pubmed:affiliation
Department of Pharmacology, Morehouse School of Medicine, Atlanta, Georgia 30310.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.