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Biochem J. Oct 15, 1994; 303(Pt 2): 461–465.
PMCID: PMC1137350

Comparison of the effects of Ca2+, adenine nucleotides and pH on the kinetic properties of mitochondrial NAD(+)-isocitrate dehydrogenase and oxoglutarate dehydrogenase from the yeast Saccharomyces cerevisiae and rat heart.

Abstract

The regulatory properties of NAD(+)-isocitrate dehydrogenase and oxoglutarate dehydrogenase in extracts of yeast and rat heart mitochondria were studied under identical conditions. Yeast NAD(+)-isocitrate dehydrogenase exhibits a low K0.5 for isocitrate and is activated by AMP and ADP, but is insensitive to ATP and Ca2+. In contrast, the rat heart NAD(+)-isocitrate dehydrogenase was insensitive to AMP, but was activated by ADP and by Ca2+ in the presence of ADP or ATP. Both yeast and rat heart oxoglutarate dehydrogenase were stimulated by ADP, but only the heart enzyme was activated by Ca2+. All the enzymes studied were activated by decreases in pH, but to differing extents. The effects of Ca2+, adenine nucleotides and pH were through K0.5 for isocitrate or 2-oxoglutarate. These observations are discussed with reference to the deduced amino acid sequences of the constituent subunits of the enzymes, where they are available.

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Selected References

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  • Anraku Y, Ohya Y, Iida H. Cell cycle control by calcium and calmodulin in Saccharomyces cerevisiae. Biochim Biophys Acta. 1991 Jul 10;1093(2-3):169–177. [PubMed]
  • Barnes LD, Kuehn GD, Atkinson DE. Yeast diphosphopyridine nucleotide specific isocitrate dehydrogenase. Purification and some properties. Biochemistry. 1971 Oct 12;10(21):3939–3944. [PubMed]
  • Cupp JR, McAlister-Henn L. NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae. J Biol Chem. 1991 Nov 25;266(33):22199–22205. [PubMed]
  • Cupp JR, McAlister-Henn L. Cloning and characterization of the gene encoding the IDH1 subunit of NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae. J Biol Chem. 1992 Aug 15;267(23):16417–16423. [PubMed]
  • Cupp JR, McAlister-Henn L. Kinetic analysis of NAD(+)-isocitrate dehydrogenase with altered isocitrate binding sites: contribution of IDH1 and IDH2 subunits to regulation and catalysis. Biochemistry. 1993 Sep 14;32(36):9323–9328. [PubMed]
  • Denton RM, McCormack JG. On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Lett. 1980 Sep 22;119(1):1–8. [PubMed]
  • Denton RM, McCormack JG. Ca2+ as a second messenger within mitochondria of the heart and other tissues. Annu Rev Physiol. 1990;52:451–466. [PubMed]
  • Denton RM, Randle PJ, Martin BR. Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase. Biochem J. 1972 Jun;128(1):161–163. [PMC free article] [PubMed]
  • Denton RM, Richards DA, Chin JG. Calcium ions and the regulation of NAD+-linked isocitrate dehydrogenase from the mitochondria of rat heart and other tissues. Biochem J. 1978 Dec 15;176(3):899–906. [PMC free article] [PubMed]
  • Guérin B, Labbe P, Somlo M. Preparation of yeast mitochondria (Saccharomyces cerevisiae) with good P/O and respiratory control ratios. Methods Enzymol. 1979;55:149–159. [PubMed]
  • Huber R, Römisch J, Paques EP. The crystal and molecular structure of human annexin V, an anticoagulant protein that binds to calcium and membranes. EMBO J. 1990 Dec;9(12):3867–3874. [PMC free article] [PubMed]
  • Huber R, Schneider M, Mayr I, Römisch J, Paques EP. The calcium binding sites in human annexin V by crystal structure analysis at 2.0 A resolution. Implications for membrane binding and calcium channel activity. FEBS Lett. 1990 Nov 26;275(1-2):15–21. [PubMed]
  • Iida H, Yagawa Y, Anraku Y. Essential role for induced Ca2+ influx followed by [Ca2+]i rise in maintaining viability of yeast cells late in the mating pheromone response pathway. A study of [Ca2+]i in single Saccharomyces cerevisiae cells with imaging of fura-2. J Biol Chem. 1990 Aug 5;265(22):13391–13399. [PubMed]
  • Koike M, Koike K. Structure, assembly and function of mammalian alpha-keto acid dehydrogenase complexes. Adv Biophys. 1976:187–227. [PubMed]
  • Koike K, Urata Y, Goto S. Cloning and nucleotide sequence of the cDNA encoding human 2-oxoglutarate dehydrogenase (lipoamide). Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1963–1967. [PMC free article] [PubMed]
  • Lawlis VB, Roche TE. Effect of micromolar Ca2+ on NADH inhibition of bovine kidney alpha-ketoglutarate dehydrogenase complex and possible role of Ca2+ in signal amplification. Mol Cell Biochem. 1980 Nov 20;32(3):147–152. [PubMed]
  • Lawson JE, Niu XD, Browning KS, Trong HL, Yan J, Reed LJ. Molecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C. Biochemistry. 1993 Sep 7;32(35):8987–8993. [PubMed]
  • McCormack JG, Denton RM. The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex. Biochem J. 1979 Jun 15;180(3):533–544. [PMC free article] [PubMed]
  • McCormack JG, Denton RM. A comparative study of the regulation of Ca2+ of the activities of the 2-oxoglutarate dehydrogenase complex and NAD+-isocitrate dehydrogenase from a variety of sources. Biochem J. 1981 May 15;196(2):619–624. [PMC free article] [PubMed]
  • McCormack JG, Halestrap AP, Denton RM. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev. 1990 Apr;70(2):391–425. [PubMed]
  • Nakajima-Shimada J, Iida H, Tsuji FI, Anraku Y. Monitoring of intracellular calcium in Saccharomyces cerevisiae with an apoaequorin cDNA expression system. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6878–6882. [PMC free article] [PubMed]
  • Nakano K, Matuda S, Yamanaka T, Tsubouchi H, Nakagawa S, Titani K, Ohta S, Miyata T. Purification and molecular cloning of succinyltransferase of the rat alpha-ketoglutarate dehydrogenase complex. Absence of a sequence motif of the putative E3 and/or E1 binding site. J Biol Chem. 1991 Oct 5;266(28):19013–19017. [PubMed]
  • Nichols BJ, Hall L, Perry AC, Denton RM. Molecular cloning and deduced amino acid sequences of the gamma-subunits of rat and monkey NAD(+)-isocitrate dehydrogenases. Biochem J. 1993 Oct 15;295(Pt 2):347–350. [PMC free article] [PubMed]
  • Otulakowski G, Robinson BH. Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases. J Biol Chem. 1987 Dec 25;262(36):17313–17318. [PubMed]
  • Ramachandran N, Colman RF. Chemical characterization of distinct subunits of pig heart DPN-specific isocitrate dehydrogenase. J Biol Chem. 1980 Sep 25;255(18):8859–8864. [PubMed]
  • Repetto B, Tzagoloff A. Structure and regulation of KGD1, the structural gene for yeast alpha-ketoglutarate dehydrogenase. Mol Cell Biol. 1989 Jun;9(6):2695–2705. [PMC free article] [PubMed]
  • Repetto B, Tzagoloff A. Structure and regulation of KGD2, the structural gene for yeast dihydrolipoyl transsuccinylase. Mol Cell Biol. 1990 Aug;10(8):4221–4232. [PMC free article] [PubMed]
  • Rutter GA. Ca2(+)-binding to citrate cycle dehydrogenases. Int J Biochem. 1990;22(10):1081–1088. [PubMed]
  • Rutter GA, Denton RM. Regulation of NAD+-linked isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase by Ca2+ ions within toluene-permeabilized rat heart mitochondria. Interactions with regulation by adenine nucleotides and NADH/NAD+ ratios. Biochem J. 1988 May 15;252(1):181–189. [PMC free article] [PubMed]
  • Rutter GA, Denton RM. The binding of Ca2+ ions to pig heart NAD+-isocitrate dehydrogenase and the 2-oxoglutarate dehydrogenase complex. Biochem J. 1989 Oct 15;263(2):453–462. [PMC free article] [PubMed]
  • Strynadka NC, James MN. Crystal structures of the helix-loop-helix calcium-binding proteins. Annu Rev Biochem. 1989;58:951–998. [PubMed]
  • Thomas AP, Diggle TA, Denton RM. Sensitivity of pyruvate dehydrogenase phosphate phosphatase to magnesium ions. Similar effects of spermine and insulin. Biochem J. 1986 Aug 15;238(1):83–91. [PMC free article] [PubMed]
  • Uribe S, Rangel P, Pardo JP. Interactions of calcium with yeast mitochondria. Cell Calcium. 1992 Apr;13(4):211–217. [PubMed]
  • Walker JE, Saraste M, Runswick MJ, Gay NJ. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1982;1(8):945–951. [PMC free article] [PubMed]

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