Aminooxyacetate inhibits gluconeogenesis by isolated chicken hepatocytes.
Although the pathway for glucose synthesis from lactate in avian liver is not thought to involve transamination steps, inhibitors of transamination (aminooxyacetate and L-2-amino-4-methoxy-trans-3-butenoic acid) block lactate gluconeogenesis by isolated chicken hepatocytes. Inhibition of glucose synthesis from lactate by aminooxyacetate is accompanied by a large increase in the lactate-to-pyruvate ratio. Oleate largely relieves inhibition by aminooxyacetate and lowers the lactate-to-pyruvate ratio. In parallel studies with rat hepatocytes, oleate did not overcome aminooxyacetate inhibition of glucose synthesis. The ratios of lactate used to glucose formed were greater than 2 with both rat and chicken hepatocytes, were increased by aminooxyacetate, and were restored toward 2 by oleate. Thus, in the absence of oleate, lactate is oxidized to provide the energy needed to meet the metabolic demand of chicken hepatocytes. Excess cytosolic reducing equivalents generated by the oxidation of lactate to pyruvate are transferred from the cytosol to the mitosol by the malate-aspartate shuttle. Aminooxyacetate inhibits the shuttle and, consequently, glucose synthesis for want of pyruvate.
D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D002645:Chickens / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats
D000085:Acetates; D007773:Lactates; D009829:Oleic Acids; D000625:Aminooxyacetic Acid