Linked Life Data

10574910

Source:http://linkedlifedata.com/resource/pubmed/id/10574910

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2000-2-3
pubmed:databankReference
pubmed:abstractText
Three novel human NAT2 alleles (NAT2*5D, NAT2*6D, and NAT2*14G) were identified and characterized in a yeast expression system. The common rapid (NAT2*4) and slow (NAT2*5B) acetylator human NAT2 alleles were also characterized for comparison. The novel recombinant NAT2 allozymes catalyzed both N- and O-acetyltransferase activities at levels comparable with NAT2 5B and significantly below NAT2 4, suggesting that they confer slow acetylation phenotype. In order to investigate the molecular mechanism of slow acetylation in the novel NAT2 alleles, we assessed mRNA and protein expression levels and protein stability. No differences were observed in NAT2 mRNA expression among the novel alleles, NAT2*4 and NAT2*5B. However NAT2 5B and NAT2 5D, but not NAT2 6D and NAT2 14G protein expression were significantly lower than NAT2 4. In contrast, NAT2 6D was slightly (3.4-fold) and NAT2 14G was substantially (29-fold) less stable than NAT2 4. These results suggest that the 341T --> C (Ile(114) --> Thr) common to the NAT2*5 cluster is sufficient for reduction in NAT2 protein expression, but that mechanisms for slow acetylator phenotype differ for NAT2 alleles that do not contain 341T --> C, such as the NAT2*6 and NAT2*14 clusters. Different mechanisms for slow acetylator phenotype in humans are consistent with multiple slow acetylator phenotypes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34519-22
pubmed:dateRevised
2010-9-8
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Novel human N-acetyltransferase 2 alleles that differ in mechanism for slow acetylator phenotype.
pubmed:affiliation
Department of Pharmacology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.