title: Aminooxyacetic acid inhibits the malate-aspartate shuttle in isolated nerve terminals and prevents the mitochondria from utilizing glycolytic substrates.
abstract: Aminooxyacetate, an inhibitor of pyridoxal-dependent enzymes, is routinely used to inhibit gamma-aminobutyrate metabolism. The bioenergetic effects of the inhibitor on guinea-pig cerebral cortical synaptosomes are investigated. It prevents the reoxidation of cytosolic NADH by the mitochondria by inhibiting the malate-aspartate shuttle, causing a 26 mV negative shift in the cytosolic NAD+/NADH redox potential, an increase in the lactate/pyruvate ratio and an inhibition of the ability of the mitochondria to utilize glycolytic pyruvate. The 3-hydroxybutyrate/acetoacetate ratio decreased significantly, indicating oxidation of the mitochondrial NAD+/NADH couple. The results are consistent with a predominant role of the malate-aspartate shuttle in the reoxidation of cytosolic NADH in isolated nerve terminals. Aminooxyacetate limits respiratory capacity and lowers mitochondrial membrane potential and synaptosomal ATP/ADP ratios to an extent similar to glucose deprivation. Thus, the inhibitor induces a functional 'hypoglycaemia' in nerve terminals and should be used with caution.
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D006019:Glycolysis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008293:Malates / Q000378:metabolism*; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D000085:Acetates; D008293:Malates; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D009243:NAD; D000625:Aminooxyacetic Acid; D001224:Aspartic Acid; C030298:malic acid; C013289:tetraphenylphosphonium