Linked Life Data

17922361

Source:http://linkedlifedata.com/resource/pubmed/id/17922361

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-1-28
pubmed:abstractText
CYP2A13 is an efficient catalyst of metabolic activation of the human carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). This study investigated the functional consequences of CYP2A13 polymorphisms that result in single amino acid substitutions. Five CYP2A13 variants, namely CYP2A13*2 (R257C), CYP2A13*5 (F453Y), CYP2A13*6 (R494C), CYP2A13*8 (D158E), and CYP2A13*9 (V323L), were expressed and evaluated for coumarin binding affinity, coumarin 7-hydroxylation, and -hydroxylation of (S)-NNN and NNK. In addition, the 133_134 Thr deletion variant, coded for by CYP2A13*3, was expressed but was not stable to the protein purification procedure. A 30-42% decrease in coumarin 7-hydroxylation catalytic efficiency was determined for R257C and D158E. No effect on coumarin binding or (S)-NNN metabolism was observed. Three variants, R257C, D158E, and V323L, had two- to threefold decreased catalytic efficiency for NNK -hydroxylation. CYP2A13 polymorphisms resulted in modest changes in coumarin 7-hydroxylation and NNK -hydroxylation activities in vitro. Although these changes are not likely to impact in vivo metabolism, these data should aid in the interpretation and design of future epidemiology studies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1439-49
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Functional characterization of CYP2A13 polymorphisms.
pubmed:affiliation
Department of Biochemistry, Molecular Biology, & Biophysics, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. murph062@umn.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural