Cytosolic lipogenic enzymes: effect of fibric acid derivatives in vitro.
The effect of fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on hepatic cytosolic enzymatic activities involved in saturated fatty acid synthesis has been estudied in vitro. From all the activities tested (fatty acid synthetase, acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, malic dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase), only acetyl-CoA carboxylase and glucose-6-phosphate dehydrogenase were significantly inhibited by fibrates, with the following order of potency: GFB > BFB > > CFB. The characteristics of the inhibition phenomena (IC50, kinetic analysis, time and protein dependence, etc) and their transcendence to the effects of fibric acid derivatives in vivo are discussed.
Sánchez
R M
RM
Department of Pharmacology, Faculty of Pharmacy, University of Barcelona, Spain.
Vázquez
M
M
Alegret
M
M
Viñals
M
M
Adzet
T
T
Merlos
M
M
Laguna
J C
JC
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002995:Clofibric Acid / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000096:biosynthesis*; D015248:Gemfibrozil / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D002995:Clofibric Acid; D015248:Gemfibrozil; D001629:Bezafibrate