Protein Information

Name pyruvate dehydrogenase (protein family or complex)
Synonyms Pyruvate dehydrogenase; Pyruvate dehydrogenases

Compound Information

Name rotenone
CAS

Reference List

PubMed Abstract RScore(About this table)
4404963 Kather H, Rivera M, Brand K: Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Biochem J. 1972 Aug;128(5):1097-102.

Rotenone, which is known to inhibit electron transport in the respiratory chain, blocked glucose breakdown at the site of pyruvate dehydrogenase.
81(1,1,1,1) Details
444478 Lichtor T, Tung B, Getz GS: Cytoplasmically inherited respiratory deficiency of a mouse fibroblast line which is resistant to rutamycin. Biochemistry. 1979 Jun 12;18(12):2582-90.

Levels of rotenone-sensitive NADH-cytochrome c reductase and pyruvate decarboxylase of the pyruvate dehydrogenase complex are markedly depressed in the mutant cells.
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176149 Batenburg JJ, Olson MS: Regulation of pyruvate dehydrogenase by fatty acid in isolated rat liver mitochondria. J Biol Chem. 1976 Mar 10;251(5):1364-70.

Addition of fatty acid caused an inactivation of pyruvate dehydrogenase in mitochondria incubated under State 3 conditions (glucose plus hexokinase), in uncoupled, oligomycin-treated mitochondria, and in rotenone-menadione-treated mitochondria, but not in uncoupled mitochondria or in mitochondria incubated under State 4 conditions.
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123530 Chiang PK, Sacktor B: Control of pyruvate dehydrogenase activity in intact cardiac mitochondria. J Biol Chem. 1975 May 10;250(9):3399-408.

Pyruvate, in the presence of rotenone, strongly inhibited inactivation.
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196589 Kerbey AL, Radcliffe PM, Randle PJ: Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A. Biochem J. 1977 Jun 15;164(3):509-19.

This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3.
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19747108 Torrentino-Madamet M, Desplans J, Travaille C, James Y, Parzy D: Microaerophilic Respiratory Metabolism of Plasmodium falciparum Mitochondrion as a Drug Target. Curr Mol Med. 2009 Sep 13.

In addition, we provide details on certain characteristics like the lack of pyruvate dehydrogenase, the existence of a rotenone-insensitive NADH-dehydrogenase, the possible existence of an alternative oxidase, and uncoupled proteins.
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20205678 Torrentino-Madamet M, Desplans J, Travaille C, James Y, Parzy D: Microaerophilic respiratory metabolism of Plasmodium falciparum mitochondrion as a drug target. Curr Mol Med. 2010 Feb 1;10(1):29-46.

In addition, we provide details on certain characteristics like the lack of pyruvate dehydrogenase, the existence of a rotenone-insensitive NADH-dehydrogenase, the possible existence of an alternative oxidase, and uncoupled proteins.
6(0,0,1,1) Details
184082 Hansford RG: Studies on the effects of coenzyme A-SH: acetyl coenzyme A, nicotinamide adenine dinucleotide: reduced nicotinamide adenine dinucleotide, and adenosine diphosphate: adenosine triphosphate ratios on the interconversion of active and inactive pyruvate dehydrogenase in isolated rat heart mitochondria. J Biol Chem. 1976 Sep 25;251(18):5483-9.

The content of coenzyme A-SH (CoASH) and acetyl-CoA of suspensions of rat heart mitochondria was stabilized by the addition of DL-carnitine and acetyl-DL-carnitine, in the presence of the respiratory inhibitor rotenone.
4(0,0,0,4) Details
1116996 Taylor SI, Mukherjee C, Jungas RL: Regulation of pyruvate dehydrogenase in isolated rat liver mitochondria. J Biol Chem. 1975 Mar 25;250(6):2028-35.

When mitochondria were incubated in State 4 with succinate and rotenone, the addition of pyruvate increased PDHa activity more than 10-fold without appreciably altering the mitochondrial ATP:ADP ratio.
4(0,0,0,4) Details
2464995 Moreno-Sanchez R, Hansford RG: Dependence of cardiac mitochondrial pyruvate dehydrogenase activity on intramitochondrial free Ca2+ concentration. Biochem J. 1988 Dec 1;256(2):403-12.

The value of the Kd of indo-1-Ca2+ in the mitochondrial matrix was determined to be 95 nM, on the basis of equilibration of [Ca2+] m with the extramitochondrial free Ca2+ ([Ca2+] o) in the presence of rotenone, nigericin, valinomycin and Br-A23187. (2) [Ca2+] m responded to energization/de-energization protocols, the inhibition of Ca2+-uptake by Ruthenium Red and the potentiation of Ca2+-efflux by Na+ in a manner which was consistent with the known kinetic properties of the mitochondrial Ca2+-transport processes. (3) The concentration gradient [Ca2+] m/[Ca2+] o was found to be near unity (0.82 +/- 0.18) when mitochondria were incubated in media containing 10 mM-Na+; the additional presence of 1 mM-Mg2+ reduced the gradient to values below unity (0.26 +/- 0.03).
3(0,0,0,3) Details
8569751 Carter TC, Coore HG: Effects of pyruvate on pyruvate dehydrogenase kinase of rat heart. . Mol Cell Biochem. 1995 Aug-Sep;149-150:71-5.

Similar behaviour was observed in mPDC from fed and starved animals when rotenone was present, pyruvate at 1 mM concentration stimulated PDHK from hearts of fed animals but was without effect at 10 mM.
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17254815 Vellucci VF, Gygax SE, Hostetter MK: Involvement of Candida albicans pyruvate dehydrogenase complex protein X (Pdx1) in filamentation. Fungal Genet Biol. 2007 Oct;44(10):979-90. Epub 2006 Dec 16.

2(0,0,0,2) Details
8417013 Zaidan E, Sims NR: Selective reductions in the activity of the pyruvate dehydrogenase complex in mitochondria isolated from brain subregions following forebrain ischemia in rats. J Cereb Blood Flow Metab. 1993 Jan;13(1):98-104.

No significant changes were observed in the activity of two other mitochondrial markers, rotenone-sensitive NADH-cytochrome c oxidoreductase and alpha-ketoglutarate dehydrogenase.
2(0,0,0,2) Details
19526285 Mallajosyula JK, Chinta SJ, Rajagopalan S, Nicholls DG, Andersen JK: Metabolic control analysis in a cellular model of elevated MAO-B: relevance to Parkinson's disease. Neurotox Res. 2009 Oct;16(3):186-93. Epub 2009 Mar 5.


In addition to KGDH, we assessed the activities and substrate-mediated respiration of complex I, pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and mitochondrial aconitase in the absence and presence of complex-specific inhibitors in specific and mixed substrate conditions in mitochondria from our MAO-B elevated cells versus controls.
1(0,0,0,1) Details
10844979 Obungu VH, Kiaira JK, Olembo NK, Njogu MR: Pathways of glucose catabolism in procyclic Trypanosoma congolense. Indian J Biochem Biophys. 1999 Oct;36(5):305-11.

Studies of respiration on glucose in procyclic Trypanosoma congolense in the presence of rotenone, antimycin, cyanide, salicylhydroxamic acid and malonate have indicated the presence of NADH dehydrogenase, cytochrome b-c1, cytochrome aa3, trypanosome alternate oxidase and NADH fumarate reductase/succinate dehydrogenase pathway that contributes electrons to coenzyme Q of the respiratory chain.
Phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase, succinate dehydrogenase, NADP (+)-linked malic enzyme, NADH fumarate reductase, malate dehydrogenase, and alpha-ketoglutarate dehydrogenase and glycerol kinase on the other hand had specific activities greater than 60 nanomoles/min/mg protein.
1(0,0,0,1) Details
3009544 Robinson BH, Ward J, Goodyer P, Baudet A: Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia. J Clin Invest. 1986 May;77(5):1422-7.

The cultured skin fibroblasts from three patients with lacticacidemia were found to have low rates of 1-[14C] pyruvate oxidation in the face of normal pyruvate dehydrogenase activity.
Measurement of Rotenone-sensitive NADH-cytochrome c reductase in mitochondrial preparations from skin fibroblasts showed that two of the patients had 14 and 18%, respectively, of control activity.
1(0,0,0,1) Details
14607783 Peterside IE, Selak MA, Simmons RA: Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats. Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1258-66.

Increased levels of manganese superoxide dismutase suggest that an antioxidant response has been mounted, and hydroxynonenal (HNE) modification of pyruvate dehydrogenase E2-(catalytic) and E3-binding protein subunits suggests that HNE-induced inactivation of this key enzyme may play a role in the mechanism of injury.
Rotenone-sensitive NADH-O2 oxidoreductase activity was similar in control and IUGR mitochondria at all ages, showing that the defect responsible for decreased pyruvate, glutamate, and alpha-ketoglutarate oxidation in IUGR liver precedes the electron transport chain and involves pyruvate and alpha-ketoglutarate dehydrogenases.
1(0,0,0,1) Details
8786242 Xu DP, Wells WW: alpha-Lipoic acid dependent regeneration of ascorbic acid from dehydroascorbic acid in rat liver mitochondria. J Bioenerg Biomembr. 1996 Feb;28(1):77-85.

Electron transport inhibitors, rotenone and antimycin A, further enhanced the dehydroascorbic acid reduction.
Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase reduced dehydroascorbic acid to ascorbic acid in an alpha-lipoic acid, coenzyme A, and pyruvate or alpha-ketoglutarate dependent fashion.
1(0,0,0,1) Details
16667685 Pascal N, Dumas R, Douce R: Comparison of the Kinetic Behavior toward Pyridine Nucleotides of NAD-Linked Dehydrogenases from Plant Mitochondria. Plant Physiol. 1990 Sep;94(1):189-193.

In this article we compare the kinetic behavior toward pyridine nucleotides (NAD (+), NADH) of NAD (+)-malic enzyme, pyruvate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and glycine decarboxylase extracted from pea (Pisum sativum) leaf and potato (Solanum tuberosum) tuber mitochondria.
It is suggested that NAD (+)-linked malic enzyme, when fully activated, is able to raise the matricial NADH level up to the required concentration to fully engage the rotenone-resistant internal NADH-dehydrogenase, whose affinity for NADH is weaker than complex I.
1(0,0,0,1) Details
19763263 Johnson F, Kaplitt MG: Novel mitochondrial substrates of omi indicate a new regulatory role in neurodegenerative disorders. PLoS One. 2009 Sep 18;4(9):e7100.

Additionally our gene expression studies, using rotenone (an inhibitor of Complex I) showed Omi expression was silenced when pdhb and idh3a were increased when a sub-lethal dose was applied.
Pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH) are two key Kreb's cycle enzymes that catalyse oxidative decarboxylation control points in mitochondrial respiration.
1(0,0,0,1) Details
15356189 Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS, Beal MF: Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci. 2004 Sep 8;24(36):7779-88.

In the absence of ADP or in the presence of rotenone, H (2) O (2) production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of alpha-ketoglutarate.
Isolated mitochondrial alpha-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H (2) O (2).
1(0,0,0,1) Details
1456730 Ofenstein JP, Dandurand DM, Kiechle FL: Assessment of mitochondrial function in cells grown in tissue culture. Ann Clin Lab Sci. 1992 Nov-Dec;22(6):406-13.

To assess mitochondrial function (pyruvate dehydrogenase [PDH] activity), cells were grown in the appropriate media to confluence, rinsed and incubated in glucose free media containing 25 microM L-lactate and [1-14C]-D,L-lactate.
The mitochondrial inhibitor rotenone (25 microM) decreased assay activity by > 75 percent in CHO and BC3H-1 cells.
1(0,0,0,1) Details
4854074 Wieland OH, Portenhauser R: Regulation of pyruvate-dehydrogenase interconversion in rat-liver mitochondria as related to the phosphorylation state of intramitochondrial adenine nucleotides. Eur J Biochem. 1974 Jun 15;45(2):577-88.

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7082719 Mita M, Hall PF: Metabolism of round spermatids from rats: lactate as the preferred substrate. Biol Reprod. 1982 Apr;26(3):445-55.


Synthesis of ATP with lactate and with pyruvate is inhibited by rotenone, rutamycin or 2,4-dinitrophenol.
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