Role of malate transport in regulating metabolism in mitochondria isolated from rabbit brain.

Abstract

Abstract— The competition between citrate synthase and aspartate amino transferase for oxaloacetate raises the question of what process controls the availability of oxaloacetate. There are two possible limiting steps (in brain mitochondria pretreated with malonate and incubated in the presence of malate), malate translocation or malate dehydrogenase activity. Incubation of mitochondria with Triton X‐100 (100 ng/ml) resulted in an increased malate penetration as measured by a filtration method, but resulted in no stimulation of aspartate formation via aspartate aminotransferase. Inclusion of p‐trifluorometh‐oxycarbonyl‐cyanide phenylhydrazone (0.3 μm) along with Triton (100 ng/ml) in the incubation medium resulted in increased aspartate formation, presumably by raising the NAD+/NADH ratio and thereby increasing the activity of malate dehydrogenase. We conclude from the data described in this report that under the conditions employed here limitation in the availability of oxaloacetate determined by malate dehydrogenase activity controls mitochondrial metabolism and that the malate carrier is not rate limiting.