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Oxoglutarate dehydrogenase complex

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375: 526: 3761: 670:. Glutamate toxicity in the brain is caused by a buildup of glutamate under times of stress. If oxoglutarate dehydrogenase activity is dysfunctional (no adaptive stress compensation), the build-up of glutamate cannot be fixed, and brain pathologies can ensue. Dysfunctional oxoglutarate dehydrogenase may also predispose the cell to damage from other toxins that can cause 618:, and has an ability to change the functioning level of mitochondria to help prevent oxidative damage. In the presence of a high concentration of free radical species, Oxoglutarate dehydrogenase undergoes fully reversible free radical mediated inhibition. In extreme cases, the enzyme can also undergo complete oxidative inhibition. 640:
Oxoglutarate dehydrogenase activity is turned off in the presence of free radicals in order to protect the enzyme from damage. Once free radicals are consumed by the cell, the enzyme's activity is turned back on via glutaredoxin. The reduction in activity of the enzyme under times of oxidative stress
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Pathophysiologies can arise when the stress becomes cumulative or develops into chronic stress. The up-regulation response that occurs after acute exposure can become exhausted if the inhibition of the enzyme complex becomes too strong. Stress in cells can cause a deregulation in the biosynthesis of
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regulators act at the E1 domain of the enzyme complex, but all three domains of the enzyme complex can be allosterically controlled. The activity of the enzyme complex is upregulated with high levels of ADP and Pi, Ca2+, and CoA-SH. The enzyme is inhibited by high ATP levels, high NADH levels, and
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are all associated with an increased oxidative stress level in the brain. Specifically for Alzheimer Disease patients, the activity of oxoglutarate dehydrogenase is significantly diminished. This leads to a possibility that the portion of the TCA cycle responsible for causing the build-up of free
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Oxoglutarate dehydrogenase plays a role in the cellular response to stress. The enzyme complex undergoes a stress-mediated temporary inhibition upon acute exposure to stress. The temporary inhibition period sparks a stronger up-regulation response, allowing an increased level of oxoglutarate
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In addition to free radicals and the mitochondrial redox state, Oxoglutarate dehydrogenase activity is also regulated by ATP/ADP ratios, the ratio of Succinyl-CoA to CoA-SH, and the concentrations of various metal ion cofactors (Mg2+, Ca2+). Many of these
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of oxidative phosphorylation. Increased Oxoglutarate dehydrogenase activation levels serve to increase the concentrations of NADH relative to NAD+. High NADH concentrations stimulate an increase in flux through oxidative phosphorylation.
1490:"Behavioral impact of the regulation of the brain 2-oxoglutarate dehydrogenase complex by synthetic phosphonate analog of 2-oxoglutarate: implications into the role of the complex in neurodegenerative diseases" 1458:
Bunik VI, Fernie AR (August 2009). "Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation".
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It is believed that the temporary inhibition of mitochondrial function stems from the reversible glutathionylation of the E2-lipoac acid domain of Oxoglutarate dehydrogenase. Glutathionylation, a form of
776:"Subunit interactions in the mammalian alpha-ketoglutarate dehydrogenase complex. Evidence for direct association of the alpha-ketoglutarate dehydrogenase and dihydrolipoamide dehydrogenase components" 734:
radical species in the brain of patients is a malfunctioning oxoglutarate dehydrogenase complex. The mechanism for disease-related inhibition of this enzyme complex remains relatively unknown.
1830: 625:, flux through the electron transport chain is reduced, and NADH production is halted. Upon consumption and removal of the free radical source, normal mitochondrial function is restored. 972:
Applegate MA, Humphries KM, Szweda LI (January 2008). "Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid".
3271: 637:. Glutathionylation "protects" the lipoic acid of the E2 domain from undergoing oxidative damage, which helps spare the Oxoglutarate dehydrogenase complex from oxidative stress. 3403: 3036: 1680: 707: 399: 1134:
Gibson GE, Blass JP, Beal MF, Bunik V (2005). "The alpha-ketoglutarate-dehydrogenase complex: a mediator between mitochondria and oxidative stress in neurodegeneration".
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Graf A, Trofimova L, Loshinskaja A, Mkrtchyan G, Strokina A, Lovat M, et al. (January 2013). "Up-regulation of 2-oxoglutarate dehydrogenase as a stress response".
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Bunik VI, Strumilo S (2009). "Regulation of Catalysis Within Cellular Network: Metabolic and Signaling Implications of the 2-Oxoglutarate Oxidative Decarboxylation".
1404:"Kinetic properties of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii evidence for the formation of a precatalytic complex with 2-oxoglutarate" 182: 1823: 1572: 3327: 2103: 201: 3302: 738: 3264: 2687: 1816: 2682: 2773: 2355: 2074: 659:
dehydrogenase activity to compensate for the acute stress exposure. Acute exposures to stress are usually at lower, tolerable levels for the cell.
922:"Glutathionylation of α-ketoglutarate dehydrogenase: the chemical nature and relative susceptibility of the cofactor lipoic acid to modification" 3011: 2441: 525: 3257: 2250: 2199: 1765: 1565: 3349: 2476: 1956: 3480: 3320: 3298: 2486: 2311: 1324:; Clarke, Joe T.R.; Laframboise, Rachel; Maranda, Bruno; Mitchell, Grant A.; Brunel‐Guitton, Catherine; Braverman, Nancy E. (2019). 500: 366: 1277:
Sorbi S, Bird ED, Blass JP (January 1983). "Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain".
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Wehbe, Zeinab; Behringer, Sidney; Alatibi, Khaled; Watkins, David; Rosenblatt, David; Spiekerkoetter, Ute; Tucci, Sara (2019).
754: 630: 633:, occurs during times of increased concentrations of free radicals, and can be undone after hydrogen peroxide consumption via 564:
for this reaction is -7.2 kcal mol. The energy needed for this oxidation is conserved in the formation of a thioester bond of
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Oxoglutarate dehydrogenase is a key control point in the citric acid cycle. It is inhibited by its products,
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that has resulted from inflammatory immune responses. Some of these inflammatory responses are explained by
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also serves to slow the flux through the electron transport chain, which slows production of free radicals.
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Strumilo S (2005). "Often ignored facts about the control of the 2-oxoglutarate dehydrogenase complex".
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Activity of the 2-oxoglutarate dehydrogenase complex is decreased in many neurodegenerative diseases.
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While an increase in flux through this pathway generates ATP for the cell, the pathway also generates
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species as a side product, which can cause oxidative stress to the cells if left to accumulate.
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Trofimova L, Lovat M, Groznaya A, Efimova E, Dunaeva T, Maslova M, et al. (October 2010).
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production. Reducing equivalents (such as NAD+/NADH) supply the electrons that run through the
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degree of important mitochondrial enzymes, such as oxoglutarate dehydrogenase complex (OGDC).
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Leung PS, Rossaro L, Davis PA, Park O, Tanaka A, Kikuchi K, et al. (November 2007).
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Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
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The OGDH E1-TPP mechanism involves the formation of a stabilized carbanion intermediate.
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Three classes of these multienzyme complexes have been characterized: one specific for
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McCartney RG, Rice JE, Sanderson SJ, Bunik V, Lindsay H, Lindsay JG (September 1998).
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By controlling the amount of available reducing equivalents generated by the
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Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
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Levtova, Alina; Waters, Paula J.; Buhas, Daniela; LĂ©vesque, SĂ©bastien;
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Shi Q, Xu H, Yu H, Zhang N, Ye Y, Estevez AG, et al. (May 2011).
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Oxoglutarate dehydrogenase is considered to be a redox sensor in the
429: 189: 85: 73: 61: 591:, Oxoglutarate dehydrogenase has a downstream regulatory effect on 492:
The reaction catalyzed by this enzyme in the citric acid cycle is:
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is an enzyme complex, most commonly known for its role in the
866:"α-Ketoglutarate dehydrogenase: a mitochondrial redox sensor" 1101:
The International Journal of Biochemistry & Cell Biology
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McLain AL, Cormier PJ, Kinter M, Szweda LI (August 2013).
749:(mtFASII) is impaired, which is the precursor reaction of 529:
Oxoglutarate dehydrogenase (α-Ketoglutarate dehydrogenase)
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Qi F, Pradhan RK, Dash RK, Beard DA (September 2011).
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This enzyme participates in three different pathways:
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Branched-chain alpha-keto acid dehydrogenase complex
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Branched-chain alpha-keto acid dehydrogenase complex
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Branched-chain alpha-keto acid dehydrogenase complex
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branched-chain alpha-keto acid dehydrogenase complex
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branched-chain alpha-keto acid dehydrogenase complex
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Phosphoenolpyruvate sugar phosphotransferase system
1711: 1627: 1592: 200: 188: 176: 171: 151: 132: 120: 108: 96: 84: 72: 60: 55: 43: 31: 26: 21: 2170:Electron-transferring-flavoprotein dehydrogenase 864:McLain AL, Szweda PA, Szweda LI (January 2011). 2075:Complex III/Coenzyme Q - cytochrome c reductase 1602:Photosynthetic reaction center complex proteins 3328:Mycothiol-dependent formaldehyde dehydrogenase 3474: 3265: 3005: 2200: 1824: 1566: 8: 1494:International Journal of Alzheimer's Disease 1402:Bunik V, Westphal AH, de Kok A (June 2000). 1063:Biochemistry and Molecular Biology Education 739:combined malonic and methylmalonic aciduria 702:. Other mitochondrial autoantigens include 3481: 3467: 3459: 3272: 3258: 3250: 3012: 2998: 2990: 2718: 2688:Mitochondrial permeability transition pore 2670: 2510: 2339: 2229: 2207: 2193: 2185: 2045: 1918: 1831: 1817: 1809: 1573: 1559: 1551: 621:When mitochondria are treated with excess 168: 1543:at the U.S. National Library of Medicine 1515: 1505: 1419: 1253: 1243: 1202: 1034: 1024: 945: 889: 840: 791: 2683:Mitochondrial membrane transport protein 915: 913: 911: 909: 815:Tretter L, Adam-Vizi V (December 2005). 373: 248: 3756: 1056: 1054: 967: 965: 766: 690:, a form of acute liver failure. These 533:This reaction proceeds in three steps: 16:Enzyme complex involved in Kreb's cycle 2442:Cholesterol side-chain cleavage enzyme 1330:Journal of Inherited Metabolic Disease 1094: 1092: 753:biosynthesis. The result is a reduced 18: 1361: 1359: 228:α-ketoglutarate dehydrogenase complex 7: 682:2-Oxo-glutarate dehydrogenase is an 2356:Coenzyme Q – cytochrome c reductase 1766:Mitochondrial trifunctional protein 1232:The Journal of Biological Chemistry 938:10.1016/j.freeradbiomed.2013.03.020 926:Free Radical Biology & Medicine 780:The Journal of Biological Chemistry 710:, which are antigens recognized by 3394:Oxoglutarate dehydrogenase complex 3350:Formate dehydrogenase (cytochrome) 2542:Oxoglutarate dehydrogenase complex 2477:Glycerol-3-phosphate dehydrogenase 2061:Complex II/Succinate dehydrogenase 1957:Pyruvate dehydrogenase phosphatase 650:high Succinyl-CoA concentrations. 220:oxoglutarate dehydrogenase complex 14: 3321:Long-chain-aldehyde dehydrogenase 2487:Carnitine palmitoyltransferase II 317:dihydrolipoyl succinyltransferase 3759: 2611:Carbamoyl phosphate synthetase I 2251:Long-chain-fatty-acid—CoA ligase 2246:Carnitine palmitoyltransferase I 1421:10.1046/j.1432-1327.2000.01387.x 1408:European Journal of Biochemistry 2472:Glutamate aspartate transporter 2085:Complex IV/Cytochrome c oxidase 1724:Carbamoyl phosphate synthase II 631:post-translational modification 553:, which forms the end product, 2589:Pyruvate dehydrogenase complex 2547:Succinyl coenzyme A synthetase 1932:Pyruvate dehydrogenase complex 1729:Aspartate carbamoyltransferase 1637:Pyruvate dehydrogenase complex 455:The following values are from 396:pyruvate dehydrogenase complex 244:pyruvate dehydrogenase complex 1: 1953:Pyruvate dehydrogenase kinase 1761:Glycine decarboxylase complex 1756:Fatty acid synthetase complex 712:anti-mitochondrial antibodies 694:appear to recognize oxidized 2393:Dihydroorotate dehydrogenase 2056:Complex I/NADH dehydrogenase 1384:10.1016/j.bbalip.2019.07.012 1113:10.1016/j.biocel.2012.07.002 1075:10.1002/bmb.2005.49403304284 882:10.3109/10715762.2010.534163 2447:Steroid 11-beta-hydroxylase 549:and subsequent transfer to 392:branched-chain α-keto acids 390:, and a third specific for 352:dihydrolipoyl dehydrogenase 3808: 3316:Acetaldehyde dehydrogenase 3065:Epidermal transglutaminase 3042:Oxoglutarate dehydrogenase 2621:N-Acetylglutamate synthase 2616:Ornithine transcarbamylase 2420:Glycerol phosphate shuttle 2286:monoamine neurotransmitter 1876:Oxoglutarate dehydrogenase 1793:Sucrase-isomaltase complex 1659:Oxoglutarate dehydrogenase 1541:Oxoglutarate+dehydrogenase 1451:10.2174/187231309789054904 745:deficiency, mitochondrial 285:oxoglutarate dehydrogenase 22:oxoglutarate dehydrogenase 3637:Michaelis–Menten kinetics 2975: 2673: 2649: 2346:oxidative phosphorylation 2041:oxidative phosphorylation 737:In the metabolic disease 688:primary biliary cirrhosis 593:oxidative phosphorylation 478: : 9 ± 3 ÎŒmol.min.mg 167: 3529:Diffusion-limited enzyme 3219:Filaggrin (Citrullinate) 2537:Isocitrate dehydrogenase 2415:Malate-aspartate shuttle 2036:electron transport chain 1996:Methylmalonyl-CoA mutase 1871:Isocitrate dehydrogenase 1751:Electron transport chain 1545:Medical Subject Headings 1439:Current Chemical Biology 793:10.1074/jbc.273.37.24158 601:electron transport chain 432:degradation (KEGG link: 386:, a second specific for 3070:Tissue transglutaminase 2584:Glutamate dehydrogenase 2371:Succinate dehydrogenase 1977:Glutamate dehydrogenase 1888:Succinate dehydrogenase 1881:Succinyl CoA synthetase 1741:P450-containing systems 1461:The Biochemical Journal 1322:Auray‐Blais, Christiane 1245:10.1074/jbc.M110.203018 1026:10.1186/1471-2091-12-53 442:metabolism (KEGG link: 3399:Pyruvate dehydrogenase 3311:Aldehyde dehydrogenase 3194:Acetylcholine receptor 3047:Pyruvate dehydrogenase 2980:mitochondrial diseases 2579:Aspartate transaminase 2236:fatty acid degradation 2020:Aspartate transaminase 1746:Cytochrome b6f complex 1136:Molecular Neurobiology 833:10.1098/rstb.2005.1764 704:pyruvate dehydrogenase 530: 458:Azotobacter vinelandii 379: 296:thiamine pyrophosphate 3622:Eadie–Hofstee diagram 3555:Allosteric regulation 3229:Sp100 nuclear antigen 2693:Mitochondrial carrier 2569:anaplerotic reactions 2405:mitochondrial shuttle 2383:pyrimidine metabolism 1586:multienzyme complexes 1291:10.1002/ana.410130116 1148:10.1385/mn:31:1-3:043 870:Free Radical Research 528: 377: 3632:Lineweaver–Burk plot 2700:Translocator protein 2557:Malate dehydrogenase 2452:Aldosterone synthase 2015:Pyruvate carboxylase 1903:Malate dehydrogenase 747:fatty acid synthesis 3440:iron–sulfur protein 2312:Intermembrane space 2165:Alternative oxidase 1969:α-ketoglutaric acid 1798:Tryptophan synthase 1788:Polyketide synthase 1507:10.4061/2010/749061 1279:Annals of Neurology 723:Parkinson's disease 719:Alzheimer's disease 540:of α-ketoglutarate, 3591:Enzyme superfamily 3524:Enzyme promiscuity 2667:Other/to be sorted 2632:alcohol metabolism 2492:Uncoupling protein 2366:NADH dehydrogenase 1473:10.1042/bj20090722 1342:10.1002/jimd.12032 731:supranuclear palsy 727:Huntington disease 700:gluten sensitivity 531: 451:Kinetic properties 411:Metabolic pathways 380: 3792:Citric acid cycle 3747: 3746: 3456: 3455: 3448:Pyruvate synthase 3247: 3246: 2987: 2986: 2971: 2970: 2714:Mitochondrial DNA 2708: 2707: 2662: 2661: 2517:citric acid cycle 2500: 2499: 2306: 2305: 2298:Monoamine oxidase 2182: 2181: 2178: 2177: 2028: 2027: 1844:Citric acid cycle 1806: 1805: 1378:(11): 1629–1643. 1195:10.1002/hep.21828 986:10.1021/bi7017464 827:(1464): 2335–45. 672:neurodegeneration 623:hydrogen peroxide 483:Citric acid cycle 420:Citric acid cycle 372: 371: 232:citric acid cycle 216: 215: 212: 211: 115:metabolic pathway 3799: 3764: 3763: 3755: 3627:Hanes–Woolf plot 3570:Enzyme activator 3565:Enzyme inhibitor 3539:Enzyme catalysis 3483: 3476: 3469: 3460: 3372:Aldehyde oxidase 3274: 3267: 3260: 3251: 3204:Apolipoprotein H 3057:Transglutaminase 3014: 3007: 3000: 2991: 2851: 2826: 2796: 2776: 2726: 2719: 2671: 2634: 2604: 2572: 2527:Citrate synthase 2520: 2511: 2465: 2435: 2408: 2386: 2349: 2340: 2320:Adenylate kinase 2291: 2267: 2239: 2230: 2209: 2202: 2195: 2186: 2046: 2007:oxaloacetic acid 1919: 1861:Citrate synthase 1833: 1826: 1819: 1810: 1575: 1568: 1561: 1552: 1529: 1519: 1509: 1484: 1454: 1433: 1423: 1388: 1387: 1363: 1354: 1353: 1317: 1311: 1310: 1274: 1268: 1267: 1257: 1247: 1223: 1217: 1216: 1206: 1174: 1168: 1167: 1131: 1125: 1124: 1096: 1087: 1086: 1058: 1049: 1048: 1038: 1028: 1013:BMC Biochemistry 1004: 998: 997: 969: 960: 959: 949: 917: 904: 903: 893: 861: 855: 854: 844: 812: 806: 805: 795: 786:(37): 24158–64. 771: 741:(CMAMMA) due to 665:neurotransmitter 471:: 0.14 ± 0.04 mM 249: 169: 19: 3807: 3806: 3802: 3801: 3800: 3798: 3797: 3796: 3772: 3771: 3770: 3758: 3750: 3748: 3743: 3655:Oxidoreductases 3641: 3617:Enzyme kinetics 3605: 3601:List of enzymes 3574: 3543: 3514:Catalytic triad 3492: 3487: 3457: 3452: 3430: 3376: 3354: 3332: 3289: 3282:oxidoreductases 3278: 3248: 3243: 3182: 3074: 3051: 3023: 3018: 2988: 2983: 2967: 2847: 2842: 2822: 2817: 2792: 2787: 2772: 2767: 2722: 2704: 2658: 2645: 2630: 2625: 2598: 2593: 2566: 2561: 2514: 2496: 2461: 2456: 2432:steroidogenesis 2429: 2424: 2402: 2397: 2380: 2375: 2343: 2329: 2325:Creatine kinase 2302: 2288: 2283: 2278: 2260: 2255: 2233: 2219: 2213: 2183: 2174: 2153: 2095: 2069: 2039: 2034: 2024: 2000: 1981: 1962: 1908: 1849: 1837: 1807: 1802: 1707: 1623: 1588: 1579: 1537: 1532: 1487: 1457: 1436: 1414:(12): 3583–91. 1401: 1397: 1395:Further reading 1392: 1391: 1365: 1364: 1357: 1319: 1318: 1314: 1276: 1275: 1271: 1238:(20): 17640–8. 1225: 1224: 1220: 1176: 1175: 1171: 1133: 1132: 1128: 1098: 1097: 1090: 1060: 1059: 1052: 1006: 1005: 1001: 971: 970: 963: 919: 918: 907: 863: 862: 858: 814: 813: 809: 773: 772: 768: 763: 680: 656: 654:Stress response 574: 546:of NAD to NADH, 538:decarboxylation 516: 497:α-ketoglutarate 490: 485: 477: 469: 453: 413: 408: 341: 306: 274: 240: 17: 12: 11: 5: 3805: 3803: 3795: 3794: 3789: 3784: 3774: 3773: 3769: 3768: 3745: 3744: 3742: 3741: 3728: 3715: 3702: 3689: 3676: 3663: 3649: 3647: 3643: 3642: 3640: 3639: 3634: 3629: 3624: 3619: 3613: 3611: 3607: 3606: 3604: 3603: 3598: 3593: 3588: 3582: 3580: 3579:Classification 3576: 3575: 3573: 3572: 3567: 3562: 3557: 3551: 3549: 3545: 3544: 3542: 3541: 3536: 3531: 3526: 3521: 3516: 3511: 3506: 3500: 3498: 3494: 3493: 3488: 3486: 3485: 3478: 3471: 3463: 3454: 3453: 3451: 3450: 3444: 3442: 3432: 3431: 3429: 3428: 3427: 3426: 3421: 3416: 3411: 3401: 3396: 3390: 3388: 3378: 3377: 3375: 3374: 3368: 3366: 3356: 3355: 3353: 3352: 3346: 3344: 3334: 3333: 3331: 3330: 3325: 3324: 3323: 3318: 3307: 3305: 3291: 3290: 3279: 3277: 3276: 3269: 3262: 3254: 3245: 3244: 3242: 3241: 3236: 3231: 3226: 3221: 3216: 3211: 3206: 3201: 3196: 3190: 3188: 3184: 3183: 3181: 3180: 3175: 3170: 3165: 3160: 3155: 3150: 3145: 3140: 3135: 3130: 3125: 3120: 3115: 3110: 3105: 3100: 3095: 3090: 3084: 3082: 3076: 3075: 3073: 3072: 3067: 3061: 3059: 3053: 3052: 3050: 3049: 3044: 3039: 3033: 3031: 3025: 3024: 3019: 3017: 3016: 3009: 3002: 2994: 2985: 2984: 2976: 2973: 2972: 2969: 2968: 2966: 2965: 2960: 2955: 2950: 2945: 2940: 2935: 2930: 2925: 2920: 2915: 2910: 2905: 2900: 2895: 2890: 2885: 2880: 2875: 2870: 2865: 2860: 2854: 2852: 2844: 2843: 2841: 2840: 2835: 2829: 2827: 2819: 2818: 2816: 2815: 2810: 2805: 2799: 2797: 2789: 2788: 2786: 2785: 2779: 2777: 2769: 2768: 2766: 2765: 2760: 2755: 2750: 2745: 2740: 2735: 2729: 2727: 2716: 2710: 2709: 2706: 2705: 2703: 2702: 2697: 2696: 2695: 2690: 2680: 2674: 2668: 2664: 2663: 2660: 2659: 2657: 2656: 2650: 2647: 2646: 2644: 2643: 2637: 2635: 2627: 2626: 2624: 2623: 2618: 2613: 2607: 2605: 2595: 2594: 2592: 2591: 2586: 2581: 2575: 2573: 2563: 2562: 2560: 2559: 2554: 2549: 2544: 2539: 2534: 2529: 2523: 2521: 2508: 2502: 2501: 2498: 2497: 2495: 2494: 2489: 2484: 2479: 2474: 2468: 2466: 2458: 2457: 2455: 2454: 2449: 2444: 2438: 2436: 2426: 2425: 2423: 2422: 2417: 2411: 2409: 2399: 2398: 2396: 2395: 2389: 2387: 2377: 2376: 2374: 2373: 2368: 2363: 2358: 2352: 2350: 2337: 2335:Inner membrane 2331: 2330: 2328: 2327: 2322: 2316: 2314: 2308: 2307: 2304: 2303: 2301: 2300: 2294: 2292: 2280: 2279: 2277: 2276: 2270: 2268: 2257: 2256: 2254: 2253: 2248: 2242: 2240: 2227: 2225:Outer membrane 2221: 2220: 2214: 2212: 2211: 2204: 2197: 2189: 2180: 2179: 2176: 2175: 2173: 2172: 2167: 2161: 2159: 2155: 2154: 2152: 2151: 2146: 2141: 2136: 2131: 2126: 2121: 2116: 2111: 2106: 2101: 2093: 2088: 2087: 2082: 2077: 2072: 2067: 2063: 2058: 2052: 2050: 2043: 2030: 2029: 2026: 2025: 2023: 2022: 2017: 2011: 2009: 2002: 2001: 1999: 1998: 1992: 1990: 1983: 1982: 1980: 1979: 1973: 1971: 1964: 1963: 1961: 1960: 1951:(regulated by 1948: 1947: 1928: 1926: 1916: 1910: 1909: 1907: 1906: 1900: 1895: 1884: 1883: 1878: 1873: 1868: 1863: 1857: 1855: 1851: 1850: 1838: 1836: 1835: 1828: 1821: 1813: 1804: 1803: 1801: 1800: 1795: 1790: 1785: 1780: 1779: 1778: 1773: 1763: 1758: 1753: 1748: 1743: 1738: 1737: 1736: 1734:Dihydroorotase 1731: 1726: 1715: 1713: 1709: 1708: 1706: 1705: 1704: 1703: 1698: 1693: 1688: 1678: 1677: 1676: 1671: 1666: 1656: 1655: 1654: 1649: 1644: 1633: 1631: 1625: 1624: 1622: 1621: 1620: 1619: 1614: 1604: 1598: 1596: 1594:Photosynthesis 1590: 1589: 1580: 1578: 1577: 1570: 1563: 1555: 1549: 1548: 1536: 1535:External links 1533: 1531: 1530: 1485: 1455: 1445:(3): 279–290. 1434: 1398: 1396: 1393: 1390: 1389: 1355: 1336:(1): 107–116. 1312: 1269: 1218: 1189:(5): 1436–42. 1169: 1142:(1–3): 43–63. 1126: 1088: 1069:(4): 284–287. 1050: 999: 961: 905: 856: 807: 765: 764: 762: 759: 686:recognized in 679: 676: 655: 652: 573: 570: 559: 558: 547: 541: 523: 522: 514: 489: 486: 484: 481: 480: 479: 475: 472: 467: 452: 449: 448: 447: 437: 427: 412: 409: 407: 404: 388:2-oxoglutarate 370: 369: 360: 353: 350: 342: 339: 335: 334: 325: 318: 315: 307: 304: 300: 299: 293: 286: 283: 275: 272: 268: 267: 262: 259: 256: 253: 239: 236: 214: 213: 210: 209: 204: 198: 197: 192: 186: 185: 180: 174: 173: 165: 164: 155: 149: 148: 137: 130: 129: 124: 118: 117: 112: 106: 105: 100: 94: 93: 88: 82: 81: 76: 70: 69: 64: 58: 57: 53: 52: 47: 41: 40: 35: 29: 28: 24: 23: 15: 13: 10: 9: 6: 4: 3: 2: 3804: 3793: 3790: 3788: 3785: 3783: 3780: 3779: 3777: 3767: 3762: 3757: 3753: 3739: 3735: 3734: 3729: 3726: 3722: 3721: 3716: 3713: 3709: 3708: 3703: 3700: 3696: 3695: 3690: 3687: 3683: 3682: 3677: 3674: 3670: 3669: 3664: 3661: 3657: 3656: 3651: 3650: 3648: 3644: 3638: 3635: 3633: 3630: 3628: 3625: 3623: 3620: 3618: 3615: 3614: 3612: 3608: 3602: 3599: 3597: 3596:Enzyme family 3594: 3592: 3589: 3587: 3584: 3583: 3581: 3577: 3571: 3568: 3566: 3563: 3561: 3560:Cooperativity 3558: 3556: 3553: 3552: 3550: 3546: 3540: 3537: 3535: 3532: 3530: 3527: 3525: 3522: 3520: 3519:Oxyanion hole 3517: 3515: 3512: 3510: 3507: 3505: 3502: 3501: 3499: 3495: 3491: 3484: 3479: 3477: 3472: 3470: 3465: 3464: 3461: 3449: 3446: 3445: 3443: 3441: 3437: 3433: 3425: 3422: 3420: 3417: 3415: 3412: 3410: 3407: 3406: 3405: 3402: 3400: 3397: 3395: 3392: 3391: 3389: 3387: 3383: 3379: 3373: 3370: 3369: 3367: 3365: 3361: 3357: 3351: 3348: 3347: 3345: 3343: 3339: 3335: 3329: 3326: 3322: 3319: 3317: 3314: 3313: 3312: 3309: 3308: 3306: 3304: 3300: 3296: 3292: 3287: 3283: 3280:Aldehyde/oxo 3275: 3270: 3268: 3263: 3261: 3256: 3255: 3252: 3240: 3239:Topoisomerase 3237: 3235: 3232: 3230: 3227: 3225: 3222: 3220: 3217: 3215: 3212: 3210: 3207: 3205: 3202: 3200: 3197: 3195: 3192: 3191: 3189: 3185: 3179: 3176: 3174: 3171: 3169: 3166: 3164: 3161: 3159: 3156: 3154: 3151: 3149: 3146: 3144: 3141: 3139: 3136: 3134: 3131: 3129: 3126: 3124: 3121: 3119: 3116: 3114: 3111: 3109: 3106: 3104: 3101: 3099: 3096: 3094: 3091: 3089: 3086: 3085: 3083: 3081: 3077: 3071: 3068: 3066: 3063: 3062: 3060: 3058: 3054: 3048: 3045: 3043: 3040: 3038: 3035: 3034: 3032: 3030: 3029:Dehydrogenase 3026: 3022: 3015: 3010: 3008: 3003: 3001: 2996: 2995: 2992: 2982: 2981: 2974: 2964: 2961: 2959: 2956: 2954: 2951: 2949: 2946: 2944: 2941: 2939: 2936: 2934: 2931: 2929: 2926: 2924: 2921: 2919: 2916: 2914: 2911: 2909: 2906: 2904: 2901: 2899: 2896: 2894: 2891: 2889: 2886: 2884: 2881: 2879: 2876: 2874: 2871: 2869: 2866: 2864: 2861: 2859: 2856: 2855: 2853: 2850: 2845: 2839: 2836: 2834: 2831: 2830: 2828: 2825: 2820: 2814: 2811: 2809: 2806: 2804: 2801: 2800: 2798: 2795: 2790: 2784: 2781: 2780: 2778: 2775: 2770: 2764: 2761: 2759: 2756: 2754: 2751: 2749: 2746: 2744: 2741: 2739: 2736: 2734: 2731: 2730: 2728: 2725: 2720: 2717: 2715: 2711: 2701: 2698: 2694: 2691: 2689: 2686: 2685: 2684: 2681: 2679: 2676: 2675: 2672: 2669: 2665: 2655: 2652: 2651: 2648: 2642: 2639: 2638: 2636: 2633: 2628: 2622: 2619: 2617: 2614: 2612: 2609: 2608: 2606: 2603: 2602: 2596: 2590: 2587: 2585: 2582: 2580: 2577: 2576: 2574: 2571: 2570: 2564: 2558: 2555: 2553: 2550: 2548: 2545: 2543: 2540: 2538: 2535: 2533: 2530: 2528: 2525: 2524: 2522: 2519: 2518: 2512: 2509: 2507: 2503: 2493: 2490: 2488: 2485: 2483: 2480: 2478: 2475: 2473: 2470: 2469: 2467: 2464: 2459: 2453: 2450: 2448: 2445: 2443: 2440: 2439: 2437: 2434: 2433: 2427: 2421: 2418: 2416: 2413: 2412: 2410: 2407: 2406: 2400: 2394: 2391: 2390: 2388: 2385: 2384: 2378: 2372: 2369: 2367: 2364: 2362: 2359: 2357: 2354: 2353: 2351: 2348: 2347: 2341: 2338: 2336: 2332: 2326: 2323: 2321: 2318: 2317: 2315: 2313: 2309: 2299: 2296: 2295: 2293: 2290: 2287: 2281: 2275: 2272: 2271: 2269: 2266: 2264: 2258: 2252: 2249: 2247: 2244: 2243: 2241: 2238: 2237: 2231: 2228: 2226: 2222: 2217: 2216:Mitochondrial 2210: 2205: 2203: 2198: 2196: 2191: 2190: 2187: 2171: 2168: 2166: 2163: 2162: 2160: 2156: 2150: 2147: 2145: 2142: 2140: 2137: 2135: 2132: 2130: 2127: 2125: 2122: 2120: 2117: 2115: 2112: 2110: 2107: 2105: 2102: 2100: 2096: 2090: 2089: 2086: 2083: 2081: 2078: 2076: 2073: 2071: 2064: 2062: 2059: 2057: 2054: 2053: 2051: 2047: 2044: 2042: 2037: 2033:Mitochondrial 2031: 2021: 2018: 2016: 2013: 2012: 2010: 2008: 2003: 1997: 1994: 1993: 1991: 1989: 1984: 1978: 1975: 1974: 1972: 1970: 1965: 1958: 1954: 1950: 1949: 1945: 1941: 1937: 1933: 1930: 1929: 1927: 1925: 1920: 1917: 1915: 1911: 1904: 1901: 1899: 1896: 1893: 1889: 1886: 1885: 1882: 1879: 1877: 1874: 1872: 1869: 1867: 1864: 1862: 1859: 1858: 1856: 1852: 1848: 1845: 1841: 1834: 1829: 1827: 1822: 1820: 1815: 1814: 1811: 1799: 1796: 1794: 1791: 1789: 1786: 1784: 1781: 1777: 1774: 1772: 1769: 1768: 1767: 1764: 1762: 1759: 1757: 1754: 1752: 1749: 1747: 1744: 1742: 1739: 1735: 1732: 1730: 1727: 1725: 1722: 1721: 1720: 1717: 1716: 1714: 1710: 1702: 1699: 1697: 1694: 1692: 1689: 1687: 1684: 1683: 1682: 1679: 1675: 1672: 1670: 1667: 1665: 1662: 1661: 1660: 1657: 1653: 1650: 1648: 1645: 1643: 1640: 1639: 1638: 1635: 1634: 1632: 1630: 1629:Dehydrogenase 1626: 1618: 1615: 1613: 1610: 1609: 1608: 1605: 1603: 1600: 1599: 1597: 1595: 1591: 1587: 1583: 1576: 1571: 1569: 1564: 1562: 1557: 1556: 1553: 1546: 1542: 1539: 1538: 1534: 1527: 1523: 1518: 1513: 1508: 1503: 1499: 1495: 1491: 1486: 1482: 1478: 1474: 1470: 1467:(3): 405–21. 1466: 1462: 1456: 1452: 1448: 1444: 1440: 1435: 1431: 1427: 1422: 1417: 1413: 1409: 1405: 1400: 1399: 1394: 1385: 1381: 1377: 1373: 1369: 1362: 1360: 1356: 1351: 1347: 1343: 1339: 1335: 1331: 1327: 1323: 1316: 1313: 1308: 1304: 1300: 1296: 1292: 1288: 1284: 1280: 1273: 1270: 1265: 1261: 1256: 1251: 1246: 1241: 1237: 1233: 1229: 1222: 1219: 1214: 1210: 1205: 1200: 1196: 1192: 1188: 1184: 1180: 1173: 1170: 1165: 1161: 1157: 1153: 1149: 1145: 1141: 1137: 1130: 1127: 1122: 1118: 1114: 1110: 1107:(1): 175–89. 1106: 1102: 1095: 1093: 1089: 1084: 1080: 1076: 1072: 1068: 1064: 1057: 1055: 1051: 1046: 1042: 1037: 1032: 1027: 1022: 1018: 1014: 1010: 1003: 1000: 995: 991: 987: 983: 979: 975: 968: 966: 962: 957: 953: 948: 943: 939: 935: 931: 927: 923: 916: 914: 912: 910: 906: 901: 897: 892: 887: 883: 879: 875: 871: 867: 860: 857: 852: 848: 843: 838: 834: 830: 826: 822: 818: 811: 808: 803: 799: 794: 789: 785: 781: 777: 770: 767: 760: 758: 756: 752: 748: 744: 740: 735: 732: 728: 724: 720: 715: 713: 709: 705: 701: 697: 693: 689: 685: 677: 675: 673: 669: 666: 660: 653: 651: 648: 642: 638: 636: 632: 626: 624: 619: 617: 612: 610: 605: 602: 598: 594: 590: 585: 583: 579: 571: 569: 567: 563: 556: 552: 548: 545: 542: 539: 536: 535: 534: 527: 521: 517: 510: 506: 502: 498: 495: 494: 493: 487: 482: 473: 470: 464: 463: 462: 460: 459: 450: 445: 441: 438: 435: 431: 428: 425: 421: 418: 417: 416: 410: 405: 403: 401: 397: 393: 389: 385: 376: 368: 364: 361: 359: 358: 354: 351: 349: 346: 343: 337: 336: 333: 329: 326: 324: 323: 319: 316: 314: 311: 308: 302: 301: 297: 294: 292: 291: 287: 284: 282: 279: 276: 270: 269: 266: 263: 260: 257: 254: 251: 250: 247: 245: 237: 235: 233: 229: 225: 221: 208: 205: 203: 199: 196: 193: 191: 187: 184: 181: 179: 175: 170: 166: 163: 159: 156: 154: 153:Gene Ontology 150: 147: 144: 141: 138: 135: 131: 128: 125: 123: 119: 116: 113: 111: 107: 104: 101: 99: 95: 92: 91:NiceZyme view 89: 87: 83: 80: 77: 75: 71: 68: 65: 63: 59: 54: 51: 48: 46: 42: 39: 36: 34: 30: 25: 20: 3787:Autoantigens 3733:Translocases 3730: 3717: 3704: 3691: 3678: 3668:Transferases 3665: 3652: 3509:Binding site 3393: 3224:Gangliosides 3080:Nucleoporins 3021:Autoantigens 2977: 2824:ATP synthase 2631: 2599: 2567: 2541: 2515: 2482:ATP synthase 2462: 2430: 2403: 2381: 2361:Cytochrome c 2344: 2284: 2274:Kynureninase 2261: 2234: 2091: 2080:Cytochrome c 1988:succinyl-CoA 1875: 1658: 1497: 1493: 1464: 1460: 1442: 1438: 1411: 1407: 1375: 1371: 1333: 1329: 1315: 1282: 1278: 1272: 1235: 1231: 1221: 1186: 1182: 1172: 1139: 1135: 1129: 1104: 1100: 1066: 1062: 1016: 1012: 1002: 980:(1): 473–8. 977: 974:Biochemistry 973: 929: 925: 876:(1): 29–36. 873: 869: 859: 824: 820: 810: 783: 779: 769: 736: 716: 681: 661: 657: 643: 639: 635:glutaredoxin 627: 620: 616:mitochondria 613: 609:free radical 606: 586: 578:succinyl CoA 575: 566:succinyl CoA 560: 555:succinyl CoA 532: 509:Succinyl CoA 491: 456: 454: 422:(KEGG link: 414: 381: 355: 320: 288: 241: 227: 223: 219: 217: 79:BRENDA entry 3504:Active site 3209:Cardiolipin 2774:Complex III 2097:synthesis: 1914:Anaplerotic 1607:Photosystem 1285:(1): 72–8. 755:lipoylation 751:lipoic acid 684:autoantigen 589:Krebs cycle 328:lipoic acid 67:IntEnz view 27:Identifiers 3776:Categories 3707:Isomerases 3681:Hydrolases 3548:Regulation 3342:cytochrome 3214:Centromere 2794:Complex IV 2601:urea cycle 2289:metabolism 2265:metabolism 2263:tryptophan 2092:Coenzyme Q 2066:Coenzyme Q 1924:acetyl-CoA 1840:Metabolism 1500:: 749061. 1183:Hepatology 761:References 692:antibodies 647:allosteric 572:Regulation 440:Tryptophan 406:Properties 332:Coenzyme A 242:Much like 136:structures 103:KEGG entry 50:9031-02-1 3586:EC number 3386:disulfide 2978:see also 2724:Complex I 2532:Aconitase 1866:Aconitase 1350:0141-8955 1019:(1): 53. 932:: 161–9. 678:Pathology 668:glutamate 544:reduction 255:EC number 56:Databases 3782:EC 1.2.4 3610:Kinetics 3534:Cofactor 3497:Activity 3234:Thrombin 2678:Frataxin 2552:Fumarase 2218:proteins 1898:Fumarase 1526:21049004 1481:19698086 1430:10848975 1307:29106528 1264:21454586 1213:17657817 1164:10787919 1156:15953811 1121:22814169 1083:86257831 1045:21943256 994:18081316 956:23567190 900:21110783 851:16321804 488:Reaction 461: : 444:MAP00380 434:MAP00310 424:MAP00020 398:and the 384:pyruvate 313:2.3.1.61 265:Cofactor 207:proteins 195:articles 183:articles 140:RCSB PDB 3766:Biology 3720:Ligases 3490:Enzymes 2838:MT-ATP8 2833:MT-ATP6 2753:MT-ND4L 2070:(CoQ10) 2049:Primary 1905:and ETC 1847:enzymes 1582:Enzymes 1517:2964918 1299:6219611 1255:3093839 1204:3731127 1036:3195097 947:3883985 891:3169906 842:1569585 802:9727038 696:protein 348:1.8.1.4 281:1.2.4.2 162:QuickGO 127:profile 110:MetaCyc 45:CAS no. 38:1.2.4.2 3752:Portal 3694:Lyases 3414:BCKDHB 3409:BCKDHA 3364:oxygen 3178:NUP214 3173:NUP205 3168:NUP210 3163:NUP188 3158:NUP160 3153:NUP155 3148:NUP153 3143:NUP133 3138:NUP107 2943:MT-TS2 2938:MT-TS1 2908:MT-TL2 2903:MT-TL1 2813:MT-CO3 2808:MT-CO2 2803:MT-CO1 2783:MT-CYB 2763:MT-ND6 2758:MT-ND5 2748:MT-ND4 2743:MT-ND3 2738:MT-ND2 2733:MT-ND1 2506:Matrix 2139:COQ10B 2134:COQ10A 1691:BCKDHB 1686:BCKDHA 1547:(MeSH) 1524:  1514:  1479:  1428:  1348:  1305:  1297:  1262:  1252:  1211:  1201:  1162:  1154:  1119:  1081:  1043:  1033:  992:  954:  944:  898:  888:  849:  839:  800:  729:, and 430:Lysine 298:(TPP) 190:PubMed 172:Search 158:AmiGO 146:PDBsum 86:ExPASy 74:BRENDA 62:IntEnz 33:EC no. 3646:Types 3436:1.2.7 3382:1.2.4 3360:1.2.3 3338:1.2.2 3295:1.2.1 3199:Actin 3187:Other 3133:NUP98 3128:NUP93 3123:NUP88 3118:NUP85 3113:NUP62 3108:NUP54 3103:NUP50 3098:NUP43 3093:NUP37 3088:NUP35 2963:MT-TY 2958:MT-TW 2953:MT-TV 2948:MT-TT 2933:MT-TR 2928:MT-TQ 2923:MT-TP 2918:MT-TN 2913:MT-TM 2898:MT-TK 2893:MT-TI 2888:MT-TH 2883:MT-TG 2878:MT-TF 2873:MT-TE 2868:MT-TD 2863:MT-TC 2858:MT-TA 2654:PMPCB 2641:ALDH2 2463:other 2158:Other 2149:PDSS2 2144:PDSS1 1854:Cycle 1776:HADHB 1771:HADHA 1712:Other 1303:S2CID 1160:S2CID 1079:S2CID 743:ACSF3 238:Units 226:) or 122:PRIAM 3738:list 3731:EC7 3725:list 3718:EC6 3712:list 3705:EC5 3699:list 3692:EC4 3686:list 3679:EC3 3673:list 3666:EC2 3660:list 3653:EC1 3303:NADP 3288:1.2) 2849:tRNA 2129:COQ9 2124:COQ7 2119:COQ6 2114:COQ5 2109:COQ4 2104:COQ3 2099:COQ2 1955:and 1892:SDHA 1669:DLST 1664:OGDH 1522:PMID 1498:2010 1477:PMID 1426:PMID 1376:1864 1346:ISSN 1295:PMID 1260:PMID 1209:PMID 1152:PMID 1117:PMID 1041:PMID 990:PMID 952:PMID 896:PMID 847:PMID 798:PMID 706:and 663:the 595:and 582:NADH 580:and 562:ΔG°' 520:NADH 322:DLST 290:OGDH 261:Gene 258:Name 252:Unit 224:OGDC 218:The 202:NCBI 143:PDBe 98:KEGG 3424:DLD 3419:DBT 3301:or 3299:NAD 2005:to 1986:to 1967:to 1922:to 1719:CAD 1701:DLD 1696:DBT 1674:DLD 1512:PMC 1502:doi 1469:doi 1465:422 1447:doi 1416:doi 1412:267 1380:doi 1338:doi 1287:doi 1250:PMC 1240:doi 1236:286 1199:PMC 1191:doi 1144:doi 1109:doi 1071:doi 1031:PMC 1021:doi 982:doi 942:PMC 934:doi 886:PMC 878:doi 837:PMC 829:doi 825:360 788:doi 784:273 597:ATP 551:CoA 505:CoA 501:NAD 476:max 367:NAD 363:FAD 357:DLD 178:PMC 134:PDB 3778:: 3438:: 3384:: 3362:: 3340:: 3297:: 3286:EC 2094:10 2068:10 1944:E3 1942:, 1940:E2 1938:, 1936:E1 1842:: 1652:E3 1647:E2 1642:E1 1617:II 1584:: 1520:. 1510:. 1496:. 1492:. 1475:. 1463:. 1441:. 1424:. 1410:. 1406:. 1374:. 1370:. 1358:^ 1344:. 1334:42 1332:. 1328:. 1301:. 1293:. 1283:13 1281:. 1258:. 1248:. 1234:. 1230:. 1207:. 1197:. 1187:46 1185:. 1181:. 1158:. 1150:. 1140:31 1138:. 1115:. 1105:45 1103:. 1091:^ 1077:. 1067:33 1065:. 1053:^ 1039:. 1029:. 1017:12 1015:. 1011:. 988:. 978:47 976:. 964:^ 950:. 940:. 930:61 928:. 924:. 908:^ 894:. 884:. 874:45 872:. 868:. 845:. 835:. 823:. 819:. 796:. 782:. 778:. 725:, 721:, 714:. 674:. 568:. 518:+ 513:CO 511:+ 507:→ 503:+ 499:+ 365:, 345:EC 330:, 310:EC 278:EC 234:. 160:/ 3754:: 3740:) 3736:( 3727:) 3723:( 3714:) 3710:( 3701:) 3697:( 3688:) 3684:( 3675:) 3671:( 3662:) 3658:( 3482:e 3475:t 3468:v 3284:( 3273:e 3266:t 3259:v 3013:e 3006:t 2999:v 2208:e 2201:t 2194:v 2038:/ 1959:) 1946:) 1934:( 1894:) 1890:( 1832:e 1825:t 1818:v 1612:I 1574:e 1567:t 1560:v 1528:. 1504:: 1483:. 1471:: 1453:. 1449:: 1443:3 1432:. 1418:: 1386:. 1382:: 1352:. 1340:: 1309:. 1289:: 1266:. 1242:: 1215:. 1193:: 1166:. 1146:: 1123:. 1111:: 1085:. 1073:: 1047:. 1023:: 996:. 984:: 958:. 936:: 902:. 880:: 853:. 831:: 804:. 790:: 557:. 515:2 474:V 468:M 466:K 446:) 436:) 426:) 340:3 338:E 305:2 303:E 273:1 271:E 222:(

Index

EC no.
1.2.4.2
CAS no.
9031-02-1
IntEnz
IntEnz view
BRENDA
BRENDA entry
ExPASy
NiceZyme view
KEGG
KEGG entry
MetaCyc
metabolic pathway
PRIAM
profile
PDB
RCSB PDB
PDBe
PDBsum
Gene Ontology
AmiGO
QuickGO
PMC
articles
PubMed
articles
NCBI
proteins
citric acid cycle

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