Evidence of multiple forms of rat liver microsomal coenzyme A ligase catalysing the formation of 2-arylpropionyl-coenzyme A thioesters.
This study has demonstrated the involvement of multiple forms of rat hepatic microsomal CoA ligases in the formation of 2-arylpropionyl-CoA thioesters. In the presence of (-)R-ibuprofen (0.1 microM-1 mM) two enzymic processes were observed, one of which exhibited enantiospecificity and apparent high affinity for the R enantiomer (Km 0.06 microM) whilst the second, a low-affinity component was non-enantiospecific. An equivalent high-affinity isoform catalysing R-flurbiprofen-CoA formation at concentrations less than 100 microM was not demonstrated. However, at higher substrate concentrations formation of both R- and S-flurbiprofenyl-CoA thioesters occurred. Marked inter-individual variation was observed in the formation of S-ibuprofen-CoA and S-flurbiprofen-CoA in the rats studied.
Knights
K M
KM
Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
Talbot
U M
UM
Baillie
T A
TA
D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism*; D004952:Esters / Q000378:metabolism; D005480:Flurbiprofen / Q000378:metabolism; D007052:Ibuprofen / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000378:metabolism*
D004952:Esters; D007527:Isoenzymes; D013438:Sulfhydryl Compounds; D005480:Flurbiprofen; D013869:Thiolester Hydrolases; D003066:Coenzyme A Ligases; D007052:Ibuprofen