Energy utilization and pyruvate as determinants of pyruvate dehydrogenase in norepinephrine-stimulated heart

The quantitative effects of norepinephrine (NE) on the active form of the cardiac pyruvate dehydrogenase complex (PDCa) and the rate of oxidative decarboxylation of pyruvate (MVPyr) were compared with those of pyruvate (Pyr). Isolated working guinea pig hearts metabolized pyruvate alone or in combination with alternative energy-providing substrates (ketone bodies, octanoate, glucose). NE produced proportional increases in PDCa and myocardial oxygen uptake (MVO2). Total PDC activity (PDC1) remained constant. The PDCa/PDC1 ratios in NE depleted hearts (reserpine pretreatment) compared well with those in hearts containing endogenous NE, provided myocardial substrate supply and MVO2 were also comparable. No evidence was obtained indicating that NE or perfusate Ca2+ can dissociate PDCa or MVPyr from MVO2, even in presence of the alternative cosubstrates. In contrast, 0.2-10 mM Pyr produced stepwise but only submaximum increases in PDCa and MVPyr, with MVO2 remaining constant. Thus, at all Pyr concentrations tested, NE stimulations of myocaridal energy utilization and MVO2 were followed by further increases in PDCa and MVPyr. Evidently, pyruvate, and particularly cellular respiration are important determinants in the regulation of cardiac PDC, also during adrenergic stimulation of the heart.