Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Oct 15;271(2):523–528. doi: 10.1042/bj2710523

Quantitative control analysis of branched-chain 2-oxo acid dehydrogenase complex activity by feedback inhibition.

B Boyer 1, R Odessey 1
PMCID: PMC1149586  PMID: 2241928

Abstract

The potential for branched-chain 2-oxo acid dehydrogenase complex (BCOADC) activity to be controlled by feedback inhibition was investigated by calculating the Elasticity Coefficients for several feedback inhibitors. We suggest that feedback inhibition is a quantitatively important regulatory mechanism by which branched-chain 2-oxo acid dehydrogenase activity is regulated. The potential for control of enzyme activity is greater for NADH than for the acyl-CoA products, and suggests that factors that alter the redox potential may physiologically regulate BCOADC activity through a feedback inhibitory mechanism in vivo. Local pH may also be an important regulatory control factor.

Full text

PDF
523

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baquer N. Z., Cascales M., McLean P., Greenbaum A. L. Effects of thyroid hormone deficiency on the distribution of hepatic metabolites and control of pathways of carbohydrate metabolism in liver and adipose tissue of the rat. Eur J Biochem. 1976 Sep 15;68(2):403–413. doi: 10.1111/j.1432-1033.1976.tb10827.x. [DOI] [PubMed] [Google Scholar]
  2. Goldbeter A., Koshland D. E., Jr Sensitivity amplification in biochemical systems. Q Rev Biophys. 1982 Aug;15(3):555–591. doi: 10.1017/s0033583500003449. [DOI] [PubMed] [Google Scholar]
  3. Heinrich R., Rapoport T. A. A linear steady-state treatment of enzymatic chains. General properties, control and effector strength. Eur J Biochem. 1974 Feb 15;42(1):89–95. doi: 10.1111/j.1432-1033.1974.tb03318.x. [DOI] [PubMed] [Google Scholar]
  4. Kacser H., Burns J. A. The control of flux. Symp Soc Exp Biol. 1973;27:65–104. [PubMed] [Google Scholar]
  5. Kobayashi K., Neely J. R. Control of maximum rates of glycolysis in rat cardiac muscle. Circ Res. 1979 Feb;44(2):166–175. doi: 10.1161/01.res.44.2.166. [DOI] [PubMed] [Google Scholar]
  6. Kohn M. C., Achs M. J., Garfinkel D. Computer simulation of metabolism in pyruvate-perfused rat heart. III. Pyruvate dehydrogenase. Am J Physiol. 1979 Sep;237(3):R167–R173. doi: 10.1152/ajpregu.1979.237.3.R167. [DOI] [PubMed] [Google Scholar]
  7. Kohn M. C., Chiang E. Metabolic network sensitivity analysis. J Theor Biol. 1982 Sep 7;98(1):109–126. doi: 10.1016/0022-5193(82)90061-3. [DOI] [PubMed] [Google Scholar]
  8. Kohn M. C., Menten L. E., Garfinkel D. A convenient computer program for fitting enzymatic rate laws to steady-state data. Comput Biomed Res. 1979 Oct;12(5):461–469. doi: 10.1016/0010-4809(79)90032-6. [DOI] [PubMed] [Google Scholar]
  9. LaNoue K. F., Bryla J., Williamson J. R. Feedback interactions in the control of citric acid cycle activity in rat heart mitochondria. J Biol Chem. 1972 Feb 10;247(3):667–679. [PubMed] [Google Scholar]
  10. Menahan L. A., Hron W. T. Regulation of acetoacetyl-CoA in isolated perfused rat hearts. Eur J Biochem. 1981 Oct;119(2):295–299. doi: 10.1111/j.1432-1033.1981.tb05607.x. [DOI] [PubMed] [Google Scholar]
  11. Moravec J. Possible relationship between tissue level of long chain acyl-CoA and the ability of the overloaded myocardium to oxidize an excess of reduced pyridine nucleotide. FEBS Lett. 1980 Apr 21;113(1):134–138. doi: 10.1016/0014-5793(80)80512-6. [DOI] [PubMed] [Google Scholar]
  12. Odessey R. Direct evidence for the inactivation of branched-chain oxo-acid dehydrogenase by enzyme phosphorylation. FEBS Lett. 1980 Dec 1;121(2):306–308. doi: 10.1016/0014-5793(80)80369-3. [DOI] [PubMed] [Google Scholar]
  13. Parker P. J., Randle P. J. Branched chain 2-oxo-acid dehydrogenase complex of rat liver. FEBS Lett. 1978 Jun 1;90(1):183–186. doi: 10.1016/0014-5793(78)80325-1. [DOI] [PubMed] [Google Scholar]
  14. Parker P. J., Randle P. J. Partial purification and properties of branched-chain 2-oxo acid dehydrogenase of ox liver. Biochem J. 1978 Jun 1;171(3):751–757. doi: 10.1042/bj1710751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Paxton R., Harris R. A. Regulation of branched-chain alpha-ketoacid dehydrogenase kinase. Arch Biochem Biophys. 1984 May 15;231(1):48–57. doi: 10.1016/0003-9861(84)90361-8. [DOI] [PubMed] [Google Scholar]
  16. Roche T. E., Cate R. L. Purification of porcine liver pyruvate dehydrogenase complex and characterization of its catalytic and regulatory properties. Arch Biochem Biophys. 1977 Oct;183(2):664–677. doi: 10.1016/0003-9861(77)90400-3. [DOI] [PubMed] [Google Scholar]
  17. Ruderman N. B., Goodman M. N. Inhibition of muscle acetoacetate utilization during diabetic ketoacidosis. Am J Physiol. 1974 Jan;226(1):136–143. doi: 10.1152/ajplegacy.1974.226.1.136. [DOI] [PubMed] [Google Scholar]
  18. Ruderman N. B., Goodman M. N. Regulation of ketone body metabolism in skeletal muscle. Am J Physiol. 1973 Jun;224(6):1391–1397. doi: 10.1152/ajplegacy.1973.224.6.1391. [DOI] [PubMed] [Google Scholar]
  19. Siess E. A., Brocks D. G., Lattke H. K., Wieland O. H. Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. Biochem J. 1977 Aug 15;166(2):225–235. doi: 10.1042/bj1660225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Taegtmeyer H. Six blind men explore an elephant: aspects of fuel metabolism and the control of tricarboxylic acid cycle activity in heart muscle. Basic Res Cardiol. 1984 May-Jun;79(3):322–336. doi: 10.1007/BF01908033. [DOI] [PubMed] [Google Scholar]
  21. Tischler M. E., Friedrichs D., Coll K., Williamson J. R. Pyridine nucleotide distributions and enzyme mass action ratios in hepatocytes from fed and starved rats. Arch Biochem Biophys. 1977 Nov;184(1):222–236. doi: 10.1016/0003-9861(77)90346-0. [DOI] [PubMed] [Google Scholar]
  22. Tischler M. E., Hecht P., Williamson J. R. Determination of mitochondrial/cytosolic metabolite gradients in isolated rat liver cells by cell disruption. Arch Biochem Biophys. 1977 May;181(1):278–293. doi: 10.1016/0003-9861(77)90506-9. [DOI] [PubMed] [Google Scholar]
  23. Westerhoff H. V., Groen A. K., Wanders R. J. Modern theories of metabolic control and their applications (review). Biosci Rep. 1984 Jan;4(1):1–22. doi: 10.1007/BF01120819. [DOI] [PubMed] [Google Scholar]
  24. Wieland O., Von Jagow-Westermann B., Stukowski B. Kinetic and regulatory properties of heart muscle pyruvate dehydrogenase. Hoppe Seylers Z Physiol Chem. 1969 Mar;350(3):329–334. doi: 10.1515/bchm2.1969.350.1.329. [DOI] [PubMed] [Google Scholar]
  25. Williamson J. R., Cooper R. H. Regulation of the citric acid cycle in mammalian systems. FEBS Lett. 1980 Aug 25;117 (Suppl):K73–K85. doi: 10.1016/0014-5793(80)80572-2. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES