Biomaterial Database

The regulation of glutamate metabolism by tricarboxylic acid-cycle activity in rat brain mitochondria. 1978

S C Dennis, and J B Clark

1. The interrelationship of metabolism of pyruvate or 3-hydroxybutyrate and glutamate transamination in rat brain mitochondria was studied. 2. If brain mitochondria are incubated in the presence of equimolar concentrations of pyruvate and glutamate and the K(+) concentration is increased from 1 to 20mm, the rate of pyruvate utilization is increased 3-fold, but the rate of production of aspartate and 2-oxoglutarate is decreased by half. 3. Brain mitochondria incubated in the presence of a fixed concentration of glutamate (0.87 or 8.7mm) but different concentrations of pyruvate (0 to 1mm) produce aspartate at rates that decrease as the pyruvate concentration is increased. At 1mm-pyruvate, the rate of aspartate production is decreased to 40% of that when zero pyruvate was present. 4. Brain mitochondria incubated in the presence of glutamate and malate alone produce 2-oxoglutarate at rates stoicheiometric with the rate of aspartate production. Both the 2-oxoglutarate and aspartate accumulate extramitochondrially. 5. Externally added 2-oxoglutarate has little inhibitory effect (K(i) approx. 31mm) on the production of aspartate from glutamate by rat brain mitochondria. 6. It is concluded that the inhibitory effect of increased C(2) flux into the tricarboxylic acid cycle on glutamate transamination is caused by competition for oxaloacetate between the transaminase and citrate synthase. 7. Evidence is provided from a reconstituted malate-aspartate (or Borst) cycle with brain mitochondria that increased C(2) flux into the tricarboxylic acid cycle from pyruvate may inhibit the reoxidation of exogenous NADH. These results are discussed in the light of the relationship between glycolysis and reoxidation of cytosolic NADH by the Borst cycle and the requirement of the brain for a continuous supply of energy.

UI	MeSH Term	Description	Entries
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.
D008297	Male		Males
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D010101	Oxygen Consumption	The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)	Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011773	Pyruvates	Derivatives of PYRUVIC ACID, including its salts and esters.
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002952	Citric Acid Cycle	A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.	Krebs Cycle,Tricarboxylic Acid Cycle,Citric Acid Cycles,Cycle, Citric Acid,Cycle, Krebs,Cycle, Tricarboxylic Acid,Cycles, Citric Acid,Cycles, Tricarboxylic Acid,Tricarboxylic Acid Cycles
D005971	Glutamates	Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.	Glutamic Acid Derivatives,Glutamic Acids,Glutaminic Acids