Biomaterial Database

Calcium and 2-oxoglutarate-mediated control of aspartate formation by rat heart mitochondria. 1994

R C Scaduto

Department of Cellular and Molecular Physiology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

Studies of the influence of calcium on the metabolism of cardiac mitochondria have indicated that calcium activates key enzymes involved in the citric acid cycle. Calcium-mediated activation of one of these enzymes, 2-oxoglutarate dehydrogenase, has been shown to cause a marked decrease in the steady-state concentration of 2-oxoglutarate in both heart and liver mitochondria. In liver, 2-oxoglutarate is a potent inhibitor of oxalacetate transamination to aspartate and activation of this enzyme by calcium-mobilizing hormones leads to a stimulation of aspartate formation and gluconeogenesis. Since mitochondrial aspartate formation is a key step in the malate/aspartate shuttle, we investigated the control of aspartate formation by cardiac mitochondria. In mitochondria incubated with glutamate and malate, activation of 2-oxoglutarate dehydrogenase by calcium led to an inhibition of aspartate formation. However, calcium caused a stimulation of aspartate production when incubations were supplemented with pyruvate as an additional substrate. Estimates of the mitochondrial redox potential (NADH/NAD+) indicated that both calcium and pyruvate increased the redox potential. The observed influence of calcium on aspartate formation was found to be due to a balance between is inhibitory effect, caused by an increased redox potential, and its stimulatory effect, caused by a decreased 2-oxoglutarate concentration. Under conditions in which the redox component was held constant, a kinetic analysis indicated that the apparent Ki for 2-oxoglutarate inhibition of aspartate formation is 0.2 mM. The data suggest that activation of cardiac 2-oxoglutarate dehydrogenase by calcium could lead to stimulation of the mitochondrial oxidation of cytosolic NADH via the malate/aspartate cycle.

UI	MeSH Term	Description	Entries
D007655	Ketoglutarate Dehydrogenase Complex		2-Keto-4-Hydroxyglutarate Dehydrogenase,2-Oxoglutarate Dehydrogenase,2-Oxoglutarate Dehydrogenase Complex,Oxoglutarate Dehydrogenase,alpha-Ketoglutarate Dehydrogenase,alpha-Ketoglutarate Dehydrogenase Complex,2 Keto 4 Hydroxyglutarate Dehydrogenase,2 Oxoglutarate Dehydrogenase,2 Oxoglutarate Dehydrogenase Complex,Complex, 2-Oxoglutarate Dehydrogenase,Complex, Ketoglutarate Dehydrogenase,Complex, alpha-Ketoglutarate Dehydrogenase,Dehydrogenase Complex, 2-Oxoglutarate,Dehydrogenase Complex, Ketoglutarate,Dehydrogenase Complex, alpha-Ketoglutarate,Dehydrogenase, 2-Keto-4-Hydroxyglutarate,Dehydrogenase, 2-Oxoglutarate,Dehydrogenase, Oxoglutarate,Dehydrogenase, alpha-Ketoglutarate,alpha Ketoglutarate Dehydrogenase,alpha Ketoglutarate Dehydrogenase Complex
D007656	Ketoglutaric Acids	A family of compounds containing an oxo group with the general structure of 1,5-pentanedioic acid. (From Lehninger, Principles of Biochemistry, 1982, p442)	Oxoglutarates,2-Ketoglutarate,2-Ketoglutaric Acid,2-Oxoglutarate,2-Oxoglutaric Acid,Calcium Ketoglutarate,Calcium alpha-Ketoglutarate,Ketoglutaric Acid,Oxogluric Acid,alpha-Ketoglutarate,alpha-Ketoglutaric Acid,alpha-Ketoglutaric Acid, Calcium Salt (2:1),alpha-Ketoglutaric Acid, Diammonium Salt,alpha-Ketoglutaric Acid, Dipotassium Salt,alpha-Ketoglutaric Acid, Disodium Salt,alpha-Ketoglutaric Acid, Monopotassium Salt,alpha-Ketoglutaric Acid, Monosodium Salt,alpha-Ketoglutaric Acid, Potassium Salt,alpha-Ketoglutaric Acid, Sodium Salt,alpha-Oxoglutarate,2 Ketoglutarate,2 Ketoglutaric Acid,2 Oxoglutarate,2 Oxoglutaric Acid,Calcium alpha Ketoglutarate,alpha Ketoglutarate,alpha Ketoglutaric Acid,alpha Ketoglutaric Acid, Diammonium Salt,alpha Ketoglutaric Acid, Dipotassium Salt,alpha Ketoglutaric Acid, Disodium Salt,alpha Ketoglutaric Acid, Monopotassium Salt,alpha Ketoglutaric Acid, Monosodium Salt,alpha Ketoglutaric Acid, Potassium Salt,alpha Ketoglutaric Acid, Sodium Salt,alpha Oxoglutarate,alpha-Ketoglutarate, Calcium
D008293	Malates	Derivatives of malic acid (the structural formula: (COO-)2CH2CHOH), including its salts and esters.
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008929	Mitochondria, Heart	The mitochondria of the myocardium.	Heart Mitochondria,Myocardial Mitochondria,Mitochondrion, Heart,Heart Mitochondrion,Mitochondria, Myocardial
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009243	NAD	A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)	Coenzyme I,DPN,Diphosphopyridine Nucleotide,Nadide,Nicotinamide-Adenine Dinucleotide,Dihydronicotinamide Adenine Dinucleotide,NADH,Adenine Dinucleotide, Dihydronicotinamide,Dinucleotide, Dihydronicotinamide Adenine,Dinucleotide, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide,Nucleotide, Diphosphopyridine
D011773	Pyruvates	Derivatives of PYRUVIC ACID, including its salts and esters.
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004140	Dinitrophenols	Organic compounds that contain two nitro groups attached to a phenol.