Linked Life Data

11854148

Source:http://linkedlifedata.com/resource/pubmed/id/11854148

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-2-20
pubmed:abstractText
N-Glucuronidation in vitro of six 4-arylalkyl-1H-imidazoles (both enantiomers of medetomidine, detomidine, atipamezole, and two other closely related compounds) by rat, dog, and human liver microsomes and by four expressed human UDP-glucuronosyltransferase isoenzymes was studied. Human liver microsomes formed N-glucuronides of 4-arylalkyl-1H-imidazoles with high activity, with apparent V(max) values ranging from 0.59 to 1.89 nmol/min/mg of protein. In comparison, apparent V(max) values for two model compounds forming the N-glucuronides 4-aminobiphenyl and amitriptyline were 5.07 and 0.56 nmol/min/mg of protein, respectively. Atipamezole showed an exceptionally low apparent K(m) value of 4.0 microM and a high specificity constant (V(max)/K(m)) of 256 compared with 4-aminobiphenyl (K(m), 265 microM; V(max)/K(m), 19) and amitriptyline (K(m), 728 microM; V(max)/K(m), 0.8). N-Glucuronidation of medetomidine was highly enantioselective in human liver microsomes; levomedetomidine exhibited a 60-fold V(max)/K(m) value compared with dexmedetomidine. Furthermore, two isomeric imidazole N-glucuronides were formed from dexmedetomidine, but only one was formed from levomedetomidine. Dog liver microsomes formed N-glucuronides of 4-arylalkyl-1H-imidazoles at a low rate and affinity, with apparent V(max) values ranging from 0.29 to 0.73 nmol/min/mg of protein and apparent K(m) values from 279 to 1640 microM. Rat liver microsomes glucuronidated these compounds at a barely detectable rate. Four expressed human UDP-glucuronosyltransferase isoenzymes (UGT1A3, UGT1A4, UGT1A6, and UGT1A9) were studied for 4-arylalkyl-1H-imidazole-conjugating activity. Only UGT1A4 glucuronidated these compounds at an activity of about 5% of that measured for 4-aminobiphenyl. The observed activity of UGT1A4 does not explain the high efficiency of glucuronidation of 4-arylalkyl-1H-imidazoles in human liver microsomes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
295-300
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11854148-Animals, pubmed-meshheading:11854148-Chromatography, High Pressure Liquid, pubmed-meshheading:11854148-Detergents, pubmed-meshheading:11854148-Dogs, pubmed-meshheading:11854148-Enzyme Activation, pubmed-meshheading:11854148-Glucuronosyltransferase, pubmed-meshheading:11854148-Humans, pubmed-meshheading:11854148-Imidazoles, pubmed-meshheading:11854148-Isoenzymes, pubmed-meshheading:11854148-Kinetics, pubmed-meshheading:11854148-Male, pubmed-meshheading:11854148-Medetomidine, pubmed-meshheading:11854148-Microsomes, Liver, pubmed-meshheading:11854148-Octoxynol, pubmed-meshheading:11854148-Rats, pubmed-meshheading:11854148-Rats, Wistar, pubmed-meshheading:11854148-Species Specificity, pubmed-meshheading:11854148-Stereoisomerism, pubmed-meshheading:11854148-Structure-Activity Relationship
pubmed:year
2002
pubmed:articleTitle
N-Glucuronidation of some 4-arylalkyl-1H-imidazoles by rat, dog, and human liver microsomes.
pubmed:affiliation
Department of Pharmacy, Division of Pharmaceutical Chemistry, University of Helsinki, Finland.
pubmed:publicationType
Journal Article, In Vitro