Calcium Ions, Hormones, and Mammalian Oxidative Metabolism
Many hormones and other external stimuli are known to act on mammalian cells by causing increases in the cytoplasmic concentration of Ca2+ . In most if not all cases, the effects brought about, e.g., contraction, secretion, and so on, require an increased supply of ATP. One possible mechanism whereby this increased energy demand may be met in some tissues is by a concommitant enhancement by Ca2+ of glycogen breakdown and hence glycolysis through the activation of phosphorylase kinase. In this paper we review the evidence for another potential mechanism whereby increases in Ca2+ may affect rates of metabolism and hence ATP synthesis, and which may be of more general importance. This mechanism involves the relay of the increases in cytoplasmic Ca2+ into the mitochondrial matrix resulting in the activation of three oxidative dehydrogenases which play key roles in the supply of NADH to the respiratory chain for ATP production.
KeywordsPyruvate Dehydrogenase Liver Mitochondrion Phosphorylase Kinase Glycogen Breakdown Mammalian Mitochondrion
Unable to display preview. Download preview PDF.
- Denton, R. M., McCormack, J. G., and Edgell, N. J., 1980, Role of calcium ions in the regulation of intramitochondrial metabolism: Effects of Na+, Mg2+ and ruthenium red on the Ca2+ -stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria, Biochem. J. 190:107–117.PubMedGoogle Scholar
- Hayat, L. H., and Crompton, M., 1982, Evidence for the existence of regulatory sites for Ca2+ on the Na+/Ca2+ carrier of cardiac mitochondria, Biochem. J. 176:627–629.Google Scholar
- McCormack, J. G., and Denton, R. M., 1984, Role of Ca2+ in the regulation of intramitochondrial metabolism in rat heart: Evidence from studies with isolated mitochondria that adrenaline activates the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes by increasing the intramitochondrial concentration of Ca2+, Biochem. J. 218:235–247.PubMedGoogle Scholar