The stereospecific incorporation of fenoprofen into rat hepatocyte and adipocyte triacylglycerols.
The formation of triacylglycerols containing fenoprofen was studied in rat isolated adipocytes and hepatocytes incubated with [3H]glycerol and R or S fenoprofen. In both hepatocytes and adipocytes there was a high-affinity enzymatic process for the synthesis of triacylglycerol containing fenoprofen which was stereospecific for the R enantiomer. The apparent Km values for R fenoprofen were 1.0 microM in adipocytes and 2.8 microM in hepatocytes. These results are consistent with the proposed stereospecific formation of R-2-arylpropionyl-CoA thioesters resulting in the stereospecific formation of R-tri-acylglycerol at clinically relevant unbound fenoprofen concentrations. In isolated hepatocytes, but not adipocytes, a second low-affinity enzymatic process for the synthesis of triacylglycerol containing fenoprofen was also observed. However, this process (Km = 3780 microM) occurred at concentrations much higher than those found in man with usual doses.
Sallustio
B C
BC
Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
Meffin
P J
PJ
Knights
K M
KM
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005279:Fenoprofen / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010666:Phenylpropionates / Q000493:pharmacokinetics*; D051381:Rats; D013237:Stereoisomerism; D014280:Triglycerides / Q000096:biosynthesis*
D010666:Phenylpropionates; D014280:Triglycerides; D005279:Fenoprofen