Effect of methionine sulfoximine on pyruvate dehydrogenase, citric acid cycle enzymes and aminotransferases in the subcellular fractions isolated from rat cerebral cortex.
The effect of acute and subacute doses of L-methionine-DL-sulfoximine (MSI) were studied on the activities of pyruvate dehydrogenase, enzymes of citric acid cycle and aspartate and alanine aminotransferases in the mitochondria, synaptosomes and cytosol of rat brain. In general, the activities of pyruvate dehydrogenase and of the citric acid cycle enzymes, except malate dehydrogenase (malate----oxaloacetate), were elevated in all 3 subcellular fractions. Malate dehydrogenase activity (malate----oxaloacetate) was suppressed in the mitochondria while the activity of this enzyme in the reverse direction was enhanced in the cytosol. Activities of aspartate and alanine aminotransferases were suppressed under these conditions. As the effects of MSI on these enzymes were similar to those observed upon the administration of ammonium salts, it is suggested that the hyperammonemic state induced by MSI might derange the operation of the malate-aspartate shuttle. Increased activities of citric acid cycle enzymes in the cytosol suggested the existence of a small population of mitochondria which was highly vulnerable either to ammonia or to MSI.
Ratnakumari
L
L
School of Life Sciences, University of Hyderabad, India.
Murthy
C R
CR
D000641:Ammonia / Q000097:blood; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D002952:Citric Acid Cycle / Q000187:drug effects*; D003292:Convulsants / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D000637:Transaminases / Q000378:metabolism*
D003292:Convulsants; D011768:Pyruvate Dehydrogenase Complex; D008717:Methionine Sulfoximine; D000641:Ammonia; D000637:Transaminases