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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1998-11-16
|
| pubmed:abstractText |
Conjugation of many primary, secondary, and tertiary amine-containing xenobiotics with glucuronic acid can result in the formation of N-glucuronide metabolites. For carcinogenic arylamines and their N-hydroxylated metabolites, N-glucuronidation can result in the formation of either inactive metabolites or labile conjugates, which can be transported to their target tissue (urinary bladder) where they may be converted to reactive metabolites. Drugs with primary amine (e.g. dapsone) or secondary amine moieties (e.g. sulfadimethoxine and clozapine) can also be metabolized to N-glucuronides. The metabolism of a number of tertiary amine-containing pharmacological agents to quaternary ammonium-linked glucuronides represents a unique and important metabolic pathway for these compounds that is highly species-dependent. This review summarizes our present knowledge of the uridine diphosphate (UDP)-glucuronosyltransferase enzymes involved in catalyzing N-glucuronide formation. Of the more than 30 UDP-glucuronosyltransferases that have been purified or cloned and expressed, many catalyze N-glucuronide formation for primary and secondary amine substrates. In contrast, only human UDP-glucuronosyltransferases 1A3 and 1A4 have been shown to catalyze quaternary ammonium-linked glucuronide formation for aliphatic tertiary amines. The structure of the UGT1 gene complex is highly conserved across species, and it appears that a mutation in the first exon encoding UDP-glucuronosyltransferase 1A4, resulting in a pseudo-gene, may explain the inability of some species to form quaternary ammonium-linked glucuronides.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0090-9556
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
26
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
860-7
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading | |
| pubmed:year |
1998
|
| pubmed:articleTitle |
Glucuronidation of amine substrates by purified and expressed UDP-glucuronosyltransferase proteins.
|
| pubmed:affiliation |
Department of Pharmacology, The University of Iowa, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Review
|