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

Abstract

In oxygen-deprived heart muscle tissue, alanine levels increase, whereas levels of glutamate and aspartate decline, and it is therefore postulated that free tissue amino acids participate in the metabolic response to cardiac hypoxia. Succinate is a hypothetical end product of anaerobic metabolism of glutamate and aspartate. To test this hypothesis in vitro isolated right ventricular papillary muscles from rabbits were individually incubated under oxygenated and hypoxic conditions. Lack of oxygen significantly augmented succinate, lactate, and alanine production, while levels of glutamate fell. Increased succinate production also 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. This finding demonstrated a close relationship between transamination of amino acids and succinate production. In addition, it is suggested that anaerobic metabolism of the amino acids glutamate and aspartate, anaerobic glycolysis, and alanine production are quantitatively related. Moreover, the two 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 one estimates the energy production by oxygen-deprived heart muscle.