Effect of clofibrate on brain mevalonate-5-pyrophosphate decarboxylase.
The effect of clofibrate on the activity of the three mevalonate-activating enzymes has been studied for the first time in brain by reactions carried out using [2-14C] mevalonic acid as substrate and 105,000 g supernatants from 14-day-old chick brain. Mevalonate-5-pyrophosphate decarboxylase was clearly inhibited, while mevalonate kinase and mevalonate-5-phosphate kinase were not significantly affected. The effect of clofibrate on decarboxylase activity was progressive with increasing concentrations (1.25-5.00 mM) of the inhibitor. A transient inhibition and a subsequent activation as a function of clofibrate concentration seemed to occur for mevalonate kinase. Direct measurements of decarboxylase activity utilizing [2-14C] pyrophosphomevalonate as the specific substrate of this enzyme corroborated these results. Kinetic studies showed that clofibrate competes with the substrate ATP.
Zafra
M F
MF
Department of Biochemistry, University of Granada, Spain.
Riquelme
S
S
Castillo
M
M
Garcia-Peregrin
E
E
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D002645:Chickens; D002994:Clofibrate / Q000494:pharmacology*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor); D017856:Phosphotransferases (Phosphate Group Acceptor)
D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase; D002262:Carboxy-Lyases; C022503:pyrophosphomevalonate decarboxylase; D002994:Clofibrate; D008798:Mevalonic Acid