By Oscar B. Garfein
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Extra info for Current Concepts in Cardiovascular Physiology
The regulation of flux through 2-oxoglutarate dehydrogenase is complex and is still not well understood. , 1981), and (2) the availability of free coenzyme A , a cofactor for the reaction (Taegtmeyer, 1983). IX. PHYSIOLOGICAL IMPLICATIONS The effects of increased cardiac work on cardiac metabolism are mediated by a feedback system which keeps energy production in step with energy utilization on a beat-to-beat basis. The effects of cardiac work have already been considered in conjunction with individual fuels for respiration.
As shown in Fig. 10, in heart muscle pyruvate may either be reduced to lactate (which completes the glycolytic pathway), transaminated to alanine, carboxylated to oxaloacetate or malate, or, most impor tantly, oxidized to acetyl-CoA. Lactate and most of the alanine are formed in the cytosol by near-equilibrium reactions and both metabolites may be washed out from the cell. In well-oxygenated working heart muscle the bulk of pyruvate C H - - CM - COOH CMj-CM-COOM co 2 1/ HOOC-CHj-^-COOH Ο Q « a l o a c e t a te MOOC-CHj -(^H-COOH OH Malate H C-C~SCoA 3 Acetyl-CoA Figure 10.
Data such as these are, however, few, and it is hoped that more will be learned on the integrative control of cardiac metabolism in the future. It needs to be stressed that control of flux through a metabolic pathway cannot be achieved by any single enzyme act ing in isolation and that regulation is a shared property of many different intraand extracellular effectors. X. PATHOPHYSIOLOGICAL IMPLICATIONS: METABOLIC ALTERATIONS IN MYOCARDIAL ISCHEMIA A. Coupling of Coronary Flow to Mechanical and Metabolic Activities It cannot be emphasized too strongly that the heart has a high rate of energy turn over.
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