Linked Life Data

6220203

Source:http://linkedlifedata.com/resource/pubmed/id/6220203

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1983-5-5
pubmed:abstractText
In the present study we have investigated the substrate specificity of the form of cytochrome P-450 catalyzing the 4-hydroxylation of debrisoquine in man by analyzing the kinetics of inhibition of this activity by potential alternative substrates for the enzyme. All three compounds for which there is good in vivo evidence for an association between their metabolism and the debrisoquine oxidation polymorphism (viz., sparteine, guanoxan and phenformin) were potent competitive inhibitors of the reaction. The Ki for sparteine was 85 microM, for guanoxan it was 30 microM, and for phenformin it was 205 microM. Two compounds, acetanilide and antipyrine, for which the in vivo evidence was against an association between their metabolism and that of debrisoquine, were weak, noncompetitive inhibitors of debrisoquine 4-hydroxylase activity. The Ki values were 1.23 mM and 19.3 mM, respectively. Two additional compounds, tolbutamide and amylobarbitone, for which the in vivo evidence was also against an association between their metabolism and the debrisoquine oxidation polymorphism, did not appreciably inhibit the reaction. In fact, amylobarbitone caused a slight stimulation of activity. It is concluded that debrisoquine 4-hydroxylase is a specific form of cytochrome P-450 with a well-defined substrate specificity. Furthermore, it should be possible to identify compounds that might be subject to an oxidation polymorphism prior to the exposure of any subjects to the compound.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
474-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Substrate specificity of the form of cytochrome P-450 catalyzing the 4-hydroxylation of debrisoquine in man.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't