The inhibition by methylmalonic acid of malate transport by the dicarboxylate carrier in rat liver mitochondria. A possible explantation for hypoglycemia in methylmalonic aciduria.
We report the effects of methylmalonic acid (MMA) on the mitochondrial transport systems for malate, alpha-oxoglutarate, and isocitrate. MMA is shown to be a substrate for all three carrier systems, and an inhibitor of the malate-phosphate exchange carrier. The effects of MMA on the metabolism of malate, oxoglutarate, and isocitrate by rat liver mitochondria are demonstrated to be mediated by the influence of MMA on the transport step. A hypothesis regarding the metabolic impairments responsible for hypoglycemia and ketonemia in methylmalonic aciduria is formulated in relation to these findings.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001692:Biological Transport; D002951:Citrates / Q000378:metabolism*; D003864:Depression, Chemical; D005943:Gluconeogenesis; D007003:Hypoglycemia / Q000209:etiology; D007535:Isomerases / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism*; D008293:Malates / Q000378:metabolism*; D008314:Malonates / Q000494:pharmacology* / Q000652:urine; D008661:Metabolism, Inborn Errors / Q000150:complications; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010101:Oxygen Consumption; D011048:Polarography; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology
D002951:Citrates; D007656:Ketoglutaric Acids; D008293:Malates; D008314:Malonates; D014475:Uncoupling Agents; D009243:NAD; D009249:NADP; D000968:Antimycin A; D007535:Isomerases