Substrate and Calcium Dependence of the Pyridine Nucleotide and Flavine Redox State in Rat Heart Mitochondria Respiring at Different Metabolic States

Abstract

The role of the mitochondrial pyridine nucleotide redox state in the regulation of oxidative phosphorylation in the perfused heart has recently received renewed attention. Measurements of oxygen consumption, high-energy phosphate metabolites and redox state of the pyridine nucleotides during alterations in heart work have challenged the classical models of regulation of oxidative phosphorylation in which regulation was considered solely dependent on changes in ADP concentration or the ATP/ADP ratio1–3. An alternative hypothesis has placed substrate dehydrogenation and the supply of redox potential as important control parameters in the regulation of cardiac oxygen consumption4–9. Increased calcium within the mitochondrial matrix upon an increase in cardiac work is thought to activate dehydrogenase activity and generate a higher matrix NADH/NAD+ ratio to a level sufficient to blunt perturbations in the ATP/ADP ratio10.