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Influence of the Malate‐Aspartate Shuttle on Oxidative Metabolism in Synaptosomes
Author(s) -
Cheeseman Andrea J.,
Clark John B.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb03044.x
Subject(s) - citric acid cycle , malate dehydrogenase , citrate synthase , mitochondrion , oxidative phosphorylation , glutamate receptor , biochemistry , nad+ kinase , glutamate dehydrogenase , cytosol , biology , tricarboxylic acid , synaptosome , chemistry , metabolism , enzyme , membrane , receptor
β‐Methyleneaspartate, a specific inhibitor of aspartate aminotransferase (EC 2.6.1.1.), was used to investigate the role of the malate‐aspartate shuttle in rat brain synaptosomes. Incubation of rat brain cytosol, “free” mitochondria, synaptosol, and synaptic mitochondria, with 2 m M β‐methyleneaspartate resulted in inhibition of aspartate aminotransferase by 69%, 67%, 49%, and 76%, respectively. The reconstituted malate‐aspartate shuttle of “free” brain mitochondria was inhibited by a similar degree (53%). As a consequence of the inhibition of the aspartate aminotransferase, and hence the malate‐aspartate shuttle, the following changes were observed in synaptosomes: decreased glucose oxidation via the pyruvate dehydrogenase reaction and the tricarboxylic acid cycle; decreased acetylcholine synthesis; and an increase in the cytosolic redox state, as measured by the lactate/pyruvate ratio. The main reason for these changes can be attributed to decreased carbon flow through the tricarboxylic acid cycle (i.e., decreased formation of oxaloacetate), rather than as a direct consequence of changes in the NAD + /NADH ratio. Malate/glutamate oxidation in “free” mitochondria was also decreased in the presence of 2 m M β‐methyleneaspartate. This is probably a result of decreased glutamate transport into mitochondria as a result of low levels of aspartate, which are needed for the exchange with glutamate by the energy‐dependent glutamate‐aspartate translocator.