Sallustio B C, Meffin P J, Knights K M
Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
Biochem Pharmacol. 1988 May 15;37(10):1919-23. doi: 10.1016/0006-2952(88)90537-0.
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.
在与[3H]甘油以及R或S型非诺洛芬一起孵育的大鼠分离脂肪细胞和肝细胞中，研究了含非诺洛芬的三酰甘油的形成。在肝细胞和脂肪细胞中，均存在一个用于合成含非诺洛芬三酰甘油的高亲和力酶促过程，该过程对R型对映体具有立体特异性。R型非诺洛芬在脂肪细胞中的表观Km值为1.0微摩尔，在肝细胞中为2.8微摩尔。这些结果与所提出的R-2-芳基丙酰辅酶A硫酯的立体特异性形成一致，从而在临床相关的未结合非诺洛芬浓度下导致R-三酰甘油的立体特异性形成。在分离的肝细胞而非脂肪细胞中，还观察到了另一个用于合成含非诺洛芬三酰甘油的低亲和力酶促过程。然而，该过程（Km = 3780微摩尔）发生时的浓度远高于在人类通常剂量下发现的浓度。
