Metabolic responses to cardiac hypoxia. Increased production of succinate by rabbit papillary muscles.

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Abstract
In O2-deprived heart muscle tissue, alanine levels increase levels of glutamate and aspartate decline, and free tissue amino acids may participate in the metabolic response to cardiac hypoxia. Succinate is a hypothetical end product of anaerobic metabolism of glutamate and aspartate. In vitro isolated right ventricular papillary muscles from rabbits were individually incubated under oxygenated and hypoxic conditions. Lack of O2 significantly augmented succinate, lactate and alanine production, while levels of glutamate fell. Increased succinate production was seen when various metabolic precursors were present in the oxygenated incubation medium. In hypoxic muscles, succinate production could be enhanced further when these precursors were present. The aminotransferase inhibitor, aminooxyacetate, reduced succinate production by hypoxic papillary muscles. A close relationship was demonstrated between transamination of amino acids and succinate production. Anaerobic metabolism of the amino acids glutamate and asparatate, anaerobic glycolysis and alanine production may be quantitatively related. The 2 reactions responsible for succinate production during hypoxia, 2-oxoglutarate dehydrogenase and fumarate reductase, are in oxidation-reduction balance and lead to substrate level phosphorylation in the citric acid cycle. Anaerobic mitochondrial metabolism, resulting in increased synthesis of succinate, must be considered when the energy production by O2-deprived heart muscle is estimated.