Effect of clofibrate on brain mevalonate-5-pyrophosphate decarboxylase |
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Authors: | M. F. Zafra S. Riquelme M. Castillo E. Garcia-Peregrin |
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Affiliation: | (1) Department of Biochemistry, University of Granada, Granada, Spain |
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Abstract: | 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 105,000g 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. |
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Keywords: | Clofibrate mevalonate-5-pyrophosphate decarboxylase brain |
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