EVIDENCE OF MULTIPLE FORMS OF RAT-LIVER MICROSOMAL COENZYME-A LIGASE CATALYZING 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 muM-1 mM) two enzymic processes were observed, one of which exhibited enantiospecificity and apparent high affinity for the R enantiomer (K(m) 0.06 muM) 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 muM 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.