The regulation of glutamate metabolism by tricarboxylic acid-cycle activity in rat brain mitochondria - PubMed (original) (raw)

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

S C Dennis et al. Biochem J. 1978.

Abstract

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.

PubMed Disclaimer

Similar articles

• Metabolism of rat brain mitochondria. Studies on the potassium ion-stimulated oxidation of pyruvate.
  Nicklas WJ, Clark JB, Williamson JR. Nicklas WJ, et al. Biochem J. 1971 Jun;123(1):83-95. doi: 10.1042/bj1230083. Biochem J. 1971. PMID: 5128666 Free PMC article.
• Calcium and 2-oxoglutarate-mediated control of aspartate formation by rat heart mitochondria.
  Scaduto RC Jr. Scaduto RC Jr. Eur J Biochem. 1994 Aug 1;223(3):751-8. doi: 10.1111/j.1432-1033.1994.tb19049.x. Eur J Biochem. 1994. PMID: 7914488
• Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart.
  Randle PJ, England PJ, Denton RM. Randle PJ, et al. Biochem J. 1970 May;117(4):677-95. doi: 10.1042/bj1170677. Biochem J. 1970. PMID: 5449122 Free PMC article.
• Regulation of the urea cycle and TCA cycle by ammonia.
  Katunuma N, Okada M, Nishii Y. Katunuma N, et al. Adv Enzyme Regul. 1966;4:317-36. doi: 10.1016/0065-2571(66)90025-2. Adv Enzyme Regul. 1966. PMID: 4229888 Review. No abstract available.
• The malate-aspartate shuttle (Borst cycle): How it started and developed into a major metabolic pathway.
  Borst P. Borst P. IUBMB Life. 2020 Nov;72(11):2241-2259. doi: 10.1002/iub.2367. Epub 2020 Sep 11. IUBMB Life. 2020. PMID: 32916028 Free PMC article. Review.

Cited by

• Reactive oxygen species production in cardiac mitochondria after complex I inhibition: Modulation by substrate-dependent regulation of the NADH/NAD(+) ratio.
  Korge P, Calmettes G, Weiss JN. Korge P, et al. Free Radic Biol Med. 2016 Jul;96:22-33. doi: 10.1016/j.freeradbiomed.2016.04.002. Epub 2016 Apr 9. Free Radic Biol Med. 2016. PMID: 27068062 Free PMC article.
• Metabolic pathways and activity-dependent modulation of glutamate concentration in the human brain.
  Mangia S, Giove F, Dinuzzo M. Mangia S, et al. Neurochem Res. 2012 Nov;37(11):2554-61. doi: 10.1007/s11064-012-0848-4. Epub 2012 Jul 31. Neurochem Res. 2012. PMID: 22846967 Free PMC article. Review.
• Energetics of inhibition: insights with a computational model of the human GABAergic neuron-astrocyte cellular complex.
  Occhipinti R, Somersalo E, Calvetti D. Occhipinti R, et al. J Cereb Blood Flow Metab. 2010 Nov;30(11):1834-46. doi: 10.1038/jcbfm.2010.107. Epub 2010 Jul 28. J Cereb Blood Flow Metab. 2010. PMID: 20664615 Free PMC article.
• Astrocytes as the glucose shunt for glutamatergic neurons at high activity: an in silico study.
  Occhipinti R, Somersalo E, Calvetti D. Occhipinti R, et al. J Neurophysiol. 2009 May;101(5):2528-38. doi: 10.1152/jn.90377.2008. Epub 2008 Oct 15. J Neurophysiol. 2009. PMID: 18922953 Free PMC article.
• Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain.
  Mintun MA, Vlassenko AG, Rundle MM, Raichle ME. Mintun MA, et al. Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):659-64. doi: 10.1073/pnas.0307457100. Epub 2004 Jan 2. Proc Natl Acad Sci U S A. 2004. PMID: 14704276 Free PMC article.

References

1. 1. Biochem J. 1976 Feb 15;154(2):423-32 - PubMed
2. 1. Biochem J. 1973 Jun;134(2):545-55 - PubMed
3. 1. J Neurochem. 1975 Sep;25(3):197-206 - PubMed
4. 1. Symp Soc Exp Biol. 1973;27:299-318 - PubMed
5. 1. J Neurochem. 1977 Mar;28(3):625-31 - PubMed

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • PubMed Central
  • Silverchair Information Systems

• Miscellaneous

  • NCI CPTAC Assay Portal