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Wiesner RJ, Rösen P, Grieshaber MK. Pathways of succinate formation and their contribution to improvement of cardiac function in the hypoxic rat heart. Biochem Med Metab Biol. 1988;40(1):19-34doi: 10.1016/0885-4505(88)90100-4.
Wiesner, R. J., Rösen, P., & Grieshaber, M. K. (1988). Pathways of succinate formation and their contribution to improvement of cardiac function in the hypoxic rat heart. Biochemical medicine and metabolic biology, 40(1), 19-34. https://doi.org/10.1016/0885-4505(88)90100-4
Wiesner, R J, et al. "Pathways of succinate formation and their contribution to improvement of cardiac function in the hypoxic rat heart." Biochemical medicine and metabolic biology vol. 40,1 (1988): 19-34. doi: https://doi.org/10.1016/0885-4505(88)90100-4
Wiesner RJ, Rösen P, Grieshaber MK. Pathways of succinate formation and their contribution to improvement of cardiac function in the hypoxic rat heart. Biochem Med Metab Biol. 1988 Aug;40(1):19-34. doi: 10.1016/0885-4505(88)90100-4. PMID: 3219228.
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Biochem Med Metab Biol. 1988 Aug;40(1):19-34. doi: 10.1016/0885-4505(88)90100-4.

Pathways of succinate formation and their contribution to improvement of cardiac function in the hypoxic rat heart.

Biochemical medicine and metabolic biology

R J Wiesner, P Rösen, M K Grieshaber

Affiliations

  1. Instutit für Zoologie IV, Universität Düsseldorf, Federal Republic of Germany.

PMID: 3219228 DOI: 10.1016/0885-4505(88)90100-4

Abstract

Hypoxia led to a dramatic acceleration of amino acid breakdown together with succinate synthesis in the rat heart. Our data do not confirm the simultaneous conversion of aspartate and glutamate to succinate, which has been repeatedly assumed in the literature (7, 8, 21, 28-30), but rather suggest that different pathways are involved during developing hypoxia and that glutamate is the sole source for anaerobic succinate production from endogenous sources in the glucose-perfused heart. Perfusion of hypoxic rat hearts with 2-oxoglutarate, malate, and fumarate (5 mM each) increased succinate formation three- to fourfold. The beneficial effects of these substances on left ventricular systolic pressure, end diastolic pressure, and time of recovery may be due to the elevated content of ATP in these hearts compared to hypoxic controls with glucose as the sole substrate. However, the maintenance of a high rate of anaerobic glycolysis in hearts perfused with 2-oxoglutarate, malate, and fumarate and not the small stimulation of succinate synthesis is considered to be the most important mechanism of cardiac protection. A proposed pathway assumes that malate, after dehydration to fumarate, may serve as an alternative electron acceptor for cytosolic NADH during conditions of oxygen deficiency, thereby cancelling glycolytic inhibition.

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