BioPAX pathway converted from "Citric acid cycle (TCA cycle)" in the Reactome database. Citric acid cycle (TCA cycle) This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp LEFT-TO-RIGHT 2.3.3.1 Acetyl-CoA + H2O + Oxaloacetate => Citrate + CoA This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Ac-CoA Acetyl coenzyme A acetyl-CoA Reactome DB_ID: 113559 mitochondrial matrix GENE ONTOLOGY GO:0005759 acetyl-CoA [ChEBI:15351] acetyl-CoA ChEBI CHEBI:15351 Reactome Database ID Release 77 113559 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113559 Reactome R-ALL-113559 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113559.3 Reactome //www.joaskin.com COMPOUND C00024 additional information MI MI:0361 H2O water Reactome DB_ID: 113521 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 77 113521 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113521 Reactome R-ALL-113521 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113521.3 COMPOUND C00001 OAA Oxaloacetate oxaloacetic acid Oxalacetic acid 2-oxobutanedioic acid Oxosuccinic acid Reactome DB_ID: 113587 oxaloacetic acid [ChEBI:30744] oxaloacetic acid ChEBI CHEBI:30744 Reactome Database ID Release 77 113587 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113587 Reactome R-ALL-113587 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113587.4 COMPOUND C00036 CoA CoA-SH coenzyme A Reactome DB_ID: 29374 coenzyme A [ChEBI:15346] coenzyme A ChEBI CHEBI:15346 Reactome Database ID Release 77 29374 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29374 Reactome R-ALL-29374 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29374.3 COMPOUND C00010 CIT Citrate citric acid 2-Hydroxy-1,2,3-propanetricarboxylic acid 2-Hydroxytricarballylic acid Reactome DB_ID: 29654 citric acid [ChEBI:30769] citric acid ChEBI CHEBI:30769 Reactome Database ID Release 77 29654 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29654 Reactome R-ALL-29654 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29654.3 COMPOUND C00158 ACTIVATION CS dimer Reactome DB_ID: 10207512 cs CS Q7ZVY5 Reactome DB_ID: 10207510 UniProt:Q7ZVY5 cs Danio rerio NCBI Taxonomy 7955 UniProt Q7ZVY5 28 EQUAL 466 EQUAL Reactome Database ID Release 77 10207510 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207510 Reactome R-DRE-70972 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70972.1 2 Reactome Database ID Release 77 10207512 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207512 Reactome R-DRE-70973 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70973.1 GENE ONTOLOGY GO:0004108 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 77 10207513 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207513 Reactome Database ID Release 77 10207515 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207515 Reactome R-DRE-70975 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70975.1 Mitochondrial citrate synthase dimer catalyzes the irreversible reaction of acetyl-CoA, water, and oxaloacetate to form citrate and coenzyme A. This reaction is the entry point of two-carbon units into the citric acid cycle. The reaction is subject to allosteric regulation. The gene encoding the human enzyme has been cloned (Goldenthal et al. 1998), but the enzyme has not been characterized in detail - its properties are inferred from those of the well-studied homologous pig enzyme (e.g., Morgunov and Srere 1998). 9792662 Pubmed 1998 Interaction between citrate synthase and malate dehydrogenase. Substrate channeling of oxaloacetate Morgunov, I Srere, PA J Biol Chem 273:29540-29544 9809442 Pubmed 1998 Cloning and molecular analysis of the human citrate synthase gene Goldenthal, MJ Marin-Garcia, J Ananthakrishnan, R Genome 41:733-738 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT 4.2.1.3 citrate <=> isocitrate This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ISCIT Isocitrate D-threo-isocitric acid (1R,2S)-1-Hydroxypropane-1,2,3-tricarboxylate Isocitric acid 1-Hydroxytricarballylic acid 1-Hydroxypropane-1,2,3-tricarboxylic acid D-erythro-Isocitric acid Reactome DB_ID: 29938 D-threo-isocitric acid [ChEBI:151] D-threo-isocitric acid ChEBI CHEBI:151 Reactome Database ID Release 77 29938 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29938 Reactome R-ALL-29938 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29938.3 COMPOUND C00451 COMPOUND C00311 ACTIVATION aco2 ACO2 A0A2R8RID5 Reactome DB_ID: 10207503 UniProt:A0A2R8RID5 aco2 UniProt A0A2R8RID5 28 EQUAL 780 EQUAL Reactome Database ID Release 77 10207503 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207503 Reactome R-DRE-70968 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70968.1 GENE ONTOLOGY GO:0003994 Reactome Database ID Release 77 10207504 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207504 Reactome Database ID Release 77 10207506 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207506 Reactome R-DRE-70971 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70971.1 Mitochondrial aconitase reversibly converts citrate to isocitrate via a cis-aconitate intermediate. Mitochondrial aconitase activity has been demonstrated in diverse human tissue extracts (Slaughter et al. 1975) and a protein homologous to the well-characterized porcine enzyme has been purified from human tissues (Baldwin et al. 1991). 1052766 Pubmed 1975 Aconitase polymorphism in man Slaughter, CA Hopkinson, DA Harris, H Ann Hum Genet 39:193-202 1946331 Pubmed 1991 Purification and partial amino acid sequence of human aconitase Baldwin, GS Seet, KL Callaghan, J Toncich, G Toh, BH Moritz, RL Rubira, MR Simpson, R Protein Seq Data Anal 4:63-67 LEFT-TO-RIGHT 4.2.1.3 isocitrate <=> citrate This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ACTIVATION Reactome Database ID Release 77 10244020 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10244020 Reactome R-DRE-450975 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-450975.1 线粒体顺乌头酸酶可逆转换isocitrate to citrate via a cis-aconitate intermediate. Mitochondrial aconitase activity has been demonstrated in diverse human tissue extracts (Slaughter et al. 1975) and a protein homologous to the well-characterized porcine enzyme has been purified from human tissues (Baldwin et al. 1991). LEFT-TO-RIGHT 1.1.1.41 isocitrate + NAD+ => alpha-ketoglutarate + CO2 + NADH + H+ [IDH3] This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp NAD NAD+ NAD(+) Nicotinamide adenine dinucleotide DPN Diphosphopyridine nucleotide NAD+ Reactome DB_ID: 113526 NAD(1-) [ChEBI:57540] NAD(1-) adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NAD(+) NAD anion ChEBI CHEBI:57540 Reactome Database ID Release 77 113526 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113526 Reactome R-ALL-113526 5 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113526.5 COMPOUND C00003 2OG 2-Oxoglutarate 2-oxoglutaric acid Oxoglutaric acid 2-Ketoglutaric acid alpha-Ketoglutaric acid 2-oxoglutarate(2-) Reactome DB_ID: 113594 2-oxoglutarate(2-) [ChEBI:16810] 2-oxoglutarate(2-) 2-ketoglutarate alpha-ketoglutarate 2-oxopentanedioic acid, ion(2-) 2-oxoglutarate ChEBI CHEBI:16810 Reactome Database ID Release 77 113594 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113594 Reactome r - - 113594 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113594.4 COMPOUND C00026 H+ hydron Reactome DB_ID: 113529 hydron [ChEBI:15378] hydron ChEBI CHEBI:15378 Reactome Database ID Release 77 113529 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113529 Reactome R-ALL-113529 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113529.4 COMPOUND C00080 CO2 carbon dioxide Reactome DB_ID: 29376 carbon dioxide [ChEBI:16526] carbon dioxide ChEBI CHEBI:16526 Reactome Database ID Release 77 29376 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29376 Reactome R-ALL-29376 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29376.3 COMPOUND C00011 NADH Reactome DB_ID: 29362 NADH(2-) [ChEBI:57945] NADH(2-) NADH dianion adenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NADH ChEBI CHEBI:57945 Reactome Database ID Release 77 29362 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29362 Reactome R-ALL-29362 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29362.3 COMPOUND C00004 ACTIVATION IDH3 complex Reactome DB_ID: 10207496 idh3a IDH3A Q6NV33 Reactome DB_ID: 10207486 UniProt:Q6NV33 idh3a UniProt Q6NV33 28 EQUAL 366 EQUAL Reactome Database ID Release 77 10207486 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207486 Reactome R-DRE-70962 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70962.1 2 idh3b IDH3B A0A2R8QPC9 Reactome DB_ID: 10207490 UniProt:A0A2R8QPC9 idh3b UniProt A0A2R8QPC9 35 EQUAL 385 EQUAL Reactome Database ID Release 77 10207490 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207490 Reactome R-DRE-70963 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70963.1 1 Mn2+ Manganese manganese(2+) Mn(II) Reactome DB_ID: 113527 manganese(2+) [ChEBI:29035] manganese(2+) Mn(2+) MANGANESE (II) ION manganese, ion (Mn2+) manganese(II) manganous ion ChEBI CHEBI:29035 Reactome Database ID Release 77 113527 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113527 Reactome R-ALL-113527 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113527.3 COMPOUND C00034 2 idh3g IDH3G F1QZA4 Reactome DB_ID: 10207494 UniProt:F1QZA4 idh3g UniProt F1QZA4 40 EQUAL 393 EQUAL Reactome Database ID Release 77 10207494 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207494 Reactome R-DRE-70964 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70964.1 1 Reactome Database ID Release 77 10207496 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207496 Reactome R-DRE-70965 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70965.1 GENE ONTOLOGY GO:0004449 Reactome Database ID Release 77 10207497 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207497 Reactome Database ID Release 77 10207499 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207499 Reactome R-DRE-70967 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70967.1 线粒体异柠檬酸脱氢酶IDH3渺位zes the irreversible reaction of isocitrate and NAD+ to form alpha ketoglutarate, CO2, and NADH + H+. The enzyme is a heteromer containing four polypeptide chains, two IDH3A, one IDH3B, and one IDH3G, and two Mn++ (Dange and Colman 2010). It is activated by ADP (Soundar et al. 2003, 2006; Bzymek and Colman 2007). This is the first of four oxidation reactions in the citric acid cycle, and the first decarboxylation. 17432878 Pubmed 2007 Role of alpha-Asp181, beta-Asp192, and gamma-Asp190 in the distinctive subunits of human NAD-specific isocitrate dehydrogenase Bzymek, KP Colman, RF Biochemistry 46:5391-7 16737955 Pubmed 2006 Identification of Mn2+-binding aspartates from alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase Soundar, S O'Hagan, M Fomulu, KS Colman, RF J Biol Chem 281:21073-81 20435888 Pubmed 2010 Each conserved active site tyr in the three subunits of human isocitrate dehydrogenase has a different function Dange, M Colman, RF J Biol Chem 285:20520-5 14555658 Pubmed 2003 Evaluation by mutagenesis of the importance of 3 arginines in alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase Soundar, S Park, JH Colman, RF J Biol Chem 278:52146-52153 ACTIVATION Reactome Database ID Release 77 70601 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70601 Reactome R-HSA-70601 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70601.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 113581 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 77 113581 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113581 Reactome R-ALL-113581 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113581.4 COMPOUND C00008 LEFT-TO-RIGHT 1.6.1.1 NADPH + NAD+ + H+ [cytosol] => NADP+ + NADH + H+ [mitochondrial matrix] This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp TPNH NADPH Reactome DB_ID: 113600 NADPH [ChEBI:16474] NADPH TPNH ChEBI CHEBI:16474 Reactome Database ID Release 77 113600 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113600 Reactome R-ALL-113600 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113600.2 COMPOUND C00005 H+ proton hydron Reactome DB_ID: 70106 cytosol GENE ONTOLOGY 去:0005829 Reactome Database ID Release 77 70106 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70106 Reactome R-ALL-70106 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70106.4 COMPOUND C00080 TPN NADP+ NADP NADP(+) Nicotinamide adenine dinucleotide phosphate beta-Nicotinamide adenine dinucleotide phosphate Triphosphopyridine nucleotide Reactome DB_ID: 113563 NADP(+) [ChEBI:18009] NADP(+) ChEBI CHEBI:18009 Reactome Database ID Release 77 113563 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113563 Reactome R-ALL-113563 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113563.4 COMPOUND C00006 ACTIVATION NNT dimer Reactome DB_ID: 10244015 mitochondrial inner membrane GENE ONTOLOGY GO:0005743 nnt NNT Q6NYQ7 Reactome DB_ID: 10244013 UniProt:Q6NYQ7 nnt UniProt Q6NYQ7 44 EQUAL 1086 EQUAL Reactome Database ID Release 77 10244013 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10244013 Reactome R-DRE-450979 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-450979.1 2 Reactome Database ID Release 77 10244015 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10244015 Reactome R-DRE-451008 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-451008.1 GENE ONTOLOGY GO:0008746 Reactome Database ID Release 77 10244016 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10244016 Reactome Database ID Release 77 10244018 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10244018 Reactome R-DRE-450971 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-450971.1 NNT (nicotinamide nucleotide transhydrogenase) associated with the inner mitochondrial membrane catalyzes the reaction of mitochondrial NADPH and NAD+ to form NADP+ and NADH. The reaction is coupled to the translocation of a proton across the inner mitochondrial membrane into the mitochondrial matrix (White et al, 2000). The active form of NNT is inferred to be a homodimer based on the known structure of its bovine homolog (Yamaguchi and Hatefi 1991). 2005110 Pubmed 1991 Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase. Membrane topography of the bovine enzyme Yamaguchi, M Hatefi, Y J Biol Chem 266:5728-35 10673423 Pubmed 2000 The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria White, SA Peake, SJ McSweeney, S Leonard, G Cotton, NP Jackson, JB Structure 8:1-12 LEFT-TO-RIGHT 1.2.1.105 alpha-ketoglutarate + CoASH + NAD+ => succinyl-CoA + CO2 + NADH + H+ Oxidative decarboxylation of alpha-ketoglutarate to succinyl CoA by alpha-ketoglutarate dehydrogenase This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp SUCC-CoA Succinyl coenzyme A succinyl-CoA(5-) Reactome DB_ID: 70958 succinyl-CoA(5-) [ChEBI:57292] succinyl-CoA(5-) S-(3-carboxy-propionyl)-CoA(5-) succinyl-coenzyme A(5-) 3'-phosphonatoadenosine 5'-{3-[(3R)-4-{[3-({2-[(3-carboxylatopropanoyl)sulfanyl]ethyl}amino)-3-oxopropyl]amino}-3-hydroxy-2,2-dimethyl-4-oxobutyl]diphosphate} succinyl-CoA S-(hydrogen succinyl)CoA(5-) succinyl-CoA pentaanion ChEBI CHEBI:57292 Reactome Database ID Release 77 70958 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70958 Reactome R-ALL-70958 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70958.4 ACTIVATION lipo-aKGDH Reactome DB_ID: 10207632 aKADH E3 dimer Reactome DB_ID: 10207284 aKADH E3 Reactome DB_ID: 10207282 FAD Flavin adenine dinucleotide Reactome DB_ID: 113596 FAD [ChEBI:16238] FAD Flavin adenine dinucleotide ChEBI CHEBI:16238 Reactome Database ID Release 77 113596 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113596 Reactome r - - 113596 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113596.2 COMPOUND C00016 1 DLD dldh Q6TNU6 Reactome DB_ID: 10207280 UniProt:Q6TNU6 dldh UniProt Q6TNU6 36 EQUAL 509 EQUAL Reactome Database ID Release 77 10207280 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207280 Reactome R-DRE-69978 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69978.1 1 Reactome Database ID Release 77 10207282 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207282 Reactome R-DRE-69979 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69979.1 2 Reactome Database ID Release 77 10207284 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207284 Reactome R-DRE-69980 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69980.1 6 aKGDH E1 dimer Reactome DB_ID: 10207623 alpha-ketoglutarate dehydrogenase E1 holoenzyme Reactome DB_ID: 10207621 OGDH ogdha A0A0R4IP01 Reactome DB_ID: 10207619 UniProt:A0A0R4IP01 ogdha UniProt A0A0R4IP01 41 EQUAL 1023 EQUAL Reactome Database ID Release 77 10207619 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207619 Reactome R-DRE-69981 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69981.1 1 TDP Thiamin diphosphate thiamine(1+) diphosphate chloride Thiamine diphosphate Thiamin pyrophosphate TPP ThPP Reactome DB_ID: 113547 thiamine(1+) diphosphate(3-) [ChEBI:58937] thiamine(1+) diphosphate(3-) thiamine diphosphate dianion thiamine diphosphate thiamine diphosphate(2-) ChEBI CHEBI:58937 Reactome Database ID Release 77 113547 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113547 Reactome R-ALL-113547 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113547.4 COMPOUND C00068 1 Reactome Database ID Release 77 10207621 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207621 Reactome R-DRE-69982 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69982.1 2 Reactome Database ID Release 77 10207623 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207623 Reactome R-DRE-69992 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69992.1 12 lipo-aKGDH E2 Reactome DB_ID: 10207630 dlst Lipo-K110-DLST F1QFQ6 Reactome DB_ID: 10207628 UniProt:F1QFQ6 dlst UniProt F1QFQ6 110 EQUAL N6-lipoyl-L-lysine MOD MOD:00127 68 EQUAL 453 EQUAL Reactome Database ID Release 77 10207628 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207628 Reactome R-DRE-69993 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69993.1 1 LIPAM lipoamide Reactome DB_ID: 29824 lipoamide [ChEBI:17460] lipoamide ChEBI CHEBI:17460 Reactome Database ID Release 77 29824 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29824 Reactome R-ALL-29824 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29824.3 COMPOUND C00248 1 Reactome Database ID Release 77 10207630 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207630 Reactome R-DRE-69995 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69995.1 24 Reactome Database ID Release 77 10207632 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207632 Reactome R-DRE-69996 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69996.1 GENE ONTOLOGY GO:0034602 Reactome Database ID Release 77 10207633 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207633 Reactome Database ID Release 77 10207932 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207932 Reactome R-DRE-71401 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-71401.1 线粒体alpha-ketoglutarate dehydrogenase complex catalyzes the reaction of alpha-ketoglutarate, CoASH, and NAD+ to form succinyl-CoA, CO2, and NADH. The enzyme complex contains multiple copies of three different proteins, E1 (OGDH), E2 (DLST), and E3 (DLD), each with distinct catalytic activities (Reed and Hackert 1990; Zhou et al 2001). The reaction starts with the oxidative decarboxylation of alpha ketoglutarate catalyzed by E1alpha and beta (alpha ketoglutarate dehydrogenase). Lipoamide cofactor associated with E1 is reduced at the same time. Next, the succinyl group derived from alpha ketoglutarate is transferred to coenzyme A in two steps catalyzed E2 (dihydrolipolyl transacetylase). Finally, the oxidized form of lipoamide is regenerated and electrons are transferred to NAD+ in two steps catalyzed by E3 (dihydrolipoyl dehydrogenase). The biochemical details of this reaction have been worked out with alpha ketoglutarate dehydrogenase complex and subunits purified from bovine tissue (McCartney et al. 1998). While all of the human proteins are known as predicted protein products of cloned genes, direct experimental evidence for their functions is available only for E3 (DLD) (Brautigam et al. 2005). 15946682 Pubmed 2005 Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations Brautigam, CA Chuang, JL Tomchick, DR Machius, M Chuang, DT J Mol Biol 350:543-52 9727038 Pubmed 1998 Subunit interactions in the mammalian alpha-ketoglutarate dehydrogenase complex. Evidence for direct association of the alpha-ketoglutarate dehydrogenase and dihydrolipoamide dehydrogenase components. McCartney, RG Rice, JE Sanderson, SJ Bunik, V Lindsay, H Lindsay, JG J Biol Chem 273:24158-64 11752427 Pubmed 2001 The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes. Zhou, ZH McCarthy, DB O'Connor, CM Reed, LJ Stoops, JK Proc Natl Acad Sci U S A 98:14802-7 2188967 Pubmed 1990 Structure-function relationships in dihydrolipoamide acyltransferases. Reed, LJ Hackert, ML J Biol Chem 265:8971-4 LEFT-TO-RIGHT 6.2.1.4 GDP + Orthophosphate + Succinyl-CoA <=> GTP + Succinate + CoA This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp Pi Orthophosphate hydrogenphosphate Phosphate Reactome DB_ID: 113548 hydrogenphosphate [ChEBI:43474] hydrogenphosphate hydrogen phosphate phosphate [PO3(OH)](2-) INORGANIC PHOSPHATE GROUP HYDROGENPHOSPHATE ION HPO4(2-) [P(OH)O3](2-) ChEBI CHEBI:43474 Reactome Database ID Release 77 113548 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113548 Reactome R-ALL-113548 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113548.4 COMPOUND C00009 GDP Guanosine 5'-diphosphate Guanosine diphosphate Reactome DB_ID: 113525 GDP [ChEBI:17552] GDP Guanosine 5'-diphosphate Guanosine diphosphate ChEBI CHEBI:17552 Reactome Database ID Release 77 113525 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113525 Reactome R-ALL-113525 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113525.2 COMPOUND C00035 GTP Guanosine 5'-triphosphate Reactome DB_ID: 113573 GTP [ChEBI:15996] GTP Guanosine 5'-triphosphate ChEBI CHEBI:15996 Reactome Database ID Release 77 113573 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113573 Reactome R-ALL-113573 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113573.2 COMPOUND C00044 SUCCA Succinate succinic acid Butanedionic acid Ethylenesuccinic acid succinate(2-) Reactome DB_ID: 113536 succinate(2-) [ChEBI:30031] succinate(2-) (-)OOC-CH2-CH2-COO(-) succinate butanedioic acid, ion(2-) butanedioate ChEBI CHEBI:30031 Reactome Database ID Release 77 113536 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113536 Reactome R-ALL-113536 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113536.4 COMPOUND C00042 ACTIVATION SUCLG1:SUCLG2 Reactome DB_ID: 10208262 Converted from EntitySet in Reactome Homologues of SUCLG2 Reactome DB_ID: 10208260 SUCLG2 SUCLG2 A0A2R8Q4D3 Reactome DB_ID: 10208250 UniProt: A0A2R8Q4D3 SUCLG2 UniProt A0A2R8Q4D3 38 EQUAL 432 EQUAL Reactome Database ID Release 77 10208250 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208250 Reactome R-DRE-156628 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156628.1 SUCLG2 SUCLG2 A0A2R8Q7E9 Reactome DB_ID: 10208254 UniProt:A0A2R8Q7E9 SUCLG2 UniProt A0A2R8Q7E9 38 EQUAL 432 EQUAL Reactome Database ID Release 77 10208254 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208254 Reactome R-DRE-156628-2 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156628-2.1 suclg2 SUCLG2 F1R7X5 Reactome DB_ID: 10208258 UniProt:F1R7X5 suclg2 UniProt F1R7X5 38 EQUAL 432 EQUAL Reactome Database ID Release 77 10208258 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208258 Reactome R-DRE-156628-3 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156628-3.1 Reactome Database ID Release 77 10208260 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208260 Reactome R-DRE-156628-4 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156628-4.1 1 suclg1 SUCLG1 B8JI00 Reactome DB_ID: 10207562 UniProt:B8JI00 suclg1 UniProt B8JI00 41 EQUAL 346 EQUAL Reactome Database ID Release 77 10207562 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207562 Reactome R-DRE-156623 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156623.1 1 Reactome Database ID Release 77 10208262 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208262 Reactome R-DRE-156627 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156627.1 GENE ONTOLOGY GO:0004776 Reactome Database ID Release 77 10208263 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208263 Reactome Database ID Release 77 10208265 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208265 Reactome R-DRE-71775 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-71775.1 Mitochondrial succinate CoA ligase (ADP-forming) catalyzes the reversible conversion of succinyl CoA to succinate plus Coenzyme A, coupled to the conversion of ADP and orthophosphate to ATP. The enzyme is a heterodimer containing SUCLG1 and SUCLA2 monomers.

The enzyme catalyzing the reaction in vertebrates is a heterodimer that occurs in two isoforms. The enzymes have been purified from pigeon and rat tissue and characterized in detail. Both isoforms, an alpha:betaA heterodimer and an alpha:betaG heterodimer, catalyze the reversible conversion of succinyl CoA to succinate plus Coenzyme A. The alpha:betaA heterodimer couples this conversion to the synthesis of ATP from ADP and orthophosphate, while the alpha:betaG heterodimer couples it to the synthesis of GTP from GDP and orthophosphate (Johnson et al. 1998a,b; Lambeth et al. 2004). Consistent with these results in model systems, patients homozygous for a mutant allele of the gene encoding the ADP enzyme beta subunit, SUCLA2, are deficient in succinyl CoA ligase activity (Elpeleg et al. 2005).

Both isoforms are found in vivo, and appear to be expressed at different levels in various tissues. Their relative contributions to the flux of carbon atoms through the TCA cycle are unknown. Genetic and biochemical data suggest that the alpha:betaA isoform may be required to catalyze the reverse reaction, conversion of succinate, Coenzyme A, and ATP to succinyl CoA, ADP, and orthophosphate for heme biosynthesis (Furuyama and Sassa 2000). 9765290 Pubmed 1998 描述的ATP, GTP-specific succinyl-CoA synthetases in pigeon. The enzymes incorporate the same alpha-subunit. Johnson, JD Muhonen, WW Lambeth, DO J Biol Chem 273:27573-9 17668387 Pubmed 2007 Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion Ostergaard, E Christensen, E Kristensen, E Mogensen, B Duno, M Shoubridge, EA Wibrand, F Am J Hum Genet 81:383-7 13181903 Pubmed 1954 Guanosine triphosphate, the primary product of phosphorylation coupled to the breakdown of succinyl coenzyme A Sanadi, DR Gibson, M Ayengar, P Biochim Biophys Acta 14:434-6 15234968 Pubmed 2004 Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues Lambeth, DO Tews, KN Adkins, S Frohlich, D Milavetz, BI J Biol Chem 279:36621-4 10727444 Pubmed 2000 Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia Furuyama, K Sassa, S J Clin Invest 105:757-64 9765291 Pubmed 1998 Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes Johnson, JD Mehus, JG Tews, KN Milavetz, BI Lambeth, DO J Biol Chem 273:27580-6 LEFT-TO-RIGHT 6.2.1.5 ADP + Orthophosphate + Succinyl-CoA <=> ATP + Succinate + CoA This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113593 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 77 113593 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113593 Reactome R-ALL-113593 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113593.4 COMPOUND C00002 ACTIVATION SUCLA2:SUCLG1 Reactome DB_ID: 10207568 sucla2 SUCLA2 Q6PBI0 Reactome DB_ID: 10207566 UniProt:Q6PBI0 sucla2 UniProt Q6PBI0 53 EQUAL 463 EQUAL Reactome Database ID Release 77 10207566 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207566 Reactome R-DRE-156624 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156624.1 1 1 Reactome Database ID Release 77 10207568 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207568 Reactome R-DRE-156625 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-156625.1 GENE ONTOLOGY GO:0004775 Reactome Database ID Release 77 10207569 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207569 Reactome Database ID Release 77 10207571 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207571 Reactome R-DRE-70997 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70997.1 Mitochondrial succinate CoA ligase (ADP-forming) catalyzes the reversible conversion of succinyl CoA to succinate plus Coenzyme A, coupled to the conversion of ADP and orthophosphate to ATP. The enzyme is a heterodimer containing SUCLG1 and SUCLA2 monomers.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp FUMA Fumarate fumaric acid Trans-butenedioic acid Reactome DB_ID: 113588 fumaric acid [ChEBI:18012] fumaric acid ChEBI CHEBI:18012 Reactome Database ID Release 77 113588 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113588 Reactome R-ALL-113588 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113588.3 COMPOUND C00122 ACTIVATION SDH complex (ox.) Reactome DB_ID: 10207555 Succinate dehydrogenase Iron Sulphur (subunit B) Reactome DB_ID: 10207545 sdhb SDHB A5PL98 Reactome DB_ID: 10207543 UniProt:A5PL98 sdhb UniProt A5PL98 29 EQUAL 280 EQUAL Reactome Database ID Release 77 10207543 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207543 Reactome R-DRE-70985 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70985.1 1 Iron Sulfur Cluster Iron Sulphur Cluster Reactome DB_ID: 113591 Reactome Database ID Release 77 113591 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113591 Reactome R-ALL-113591 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113591.2 ChEBI 30408 1 Reactome Database ID Release 77 10207545 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207545 Reactome R-DRE-70987 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70987.1 1 sdhc SDHC B0S5Q2 Reactome DB_ID: 10207549 UniProt:B0S5Q2 sdhc UniProt B0S5Q2 30 EQUAL 169 EQUAL Reactome Database ID Release 77 10207549 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207549 Reactome R-DRE-70988 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70988.1 1 SDHD sdhdb Q68FN7 Reactome DB_ID: 10207553 UniProt:Q68FN7 sdhdb UniProt Q68FN7 57 EQUAL 159 EQUAL Reactome Database ID Release 77 10207553 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207553 Reactome R-DRE-70989 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70989.1 1 Succinate dehydrogenase flavoprotein (subunit A), oxidised Reactome DB_ID: 10207539 FAD Flavin adenine dinucleotide Reactome DB_ID: 113597 Reactome Database ID Release 77 113597 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113597 Reactome r - - 113597 2 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113597.2 COMPOUND C00016 1 sdha SDHA Q7ZVF3 Reactome DB_ID: 10207537 UniProt:Q7ZVF3 sdha UniProt Q7ZVF3 44 EQUAL 664 EQUAL Reactome Database ID Release 77 10207537 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207537 Reactome R-DRE-70983 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70983.1 1 Reactome Database ID Release 77 10207539 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207539 Reactome R-DRE-70984 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70984.1 1 Reactome Database ID Release 77 10207555 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207555 Reactome R-DRE-70990 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70990.1 GENE ONTOLOGY GO:0008177 Reactome Database ID Release 77 10207556 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207556 Reactome Database ID Release 77 10207558 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207558 Reactome R-DRE-70994 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70994.1 The succinate dehydrogenase complex, associated with the inner mitochondrial membrane, catalyzes the dehydrogenation of succinate to fumarate, reducing the FAD cofactor bound to the enzyme. This redox potential is then used in the electron transfer chain to drive a proton motive force to generate ATP. 16143825 Pubmed 2005 Succinate dehydrogenase deficiency in human Briere, JJ Favier, J El Ghouzzi, V Djouadi, F Benit, P Gimenez, AP Rustin, P Cell Mol Life Sci 62:2317â€“2324 LEFT-TO-RIGHT 4.2.1.2 Fumarate + H2O <=> (S)-Malate This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp MAL (S)-Malate (S)-malic acid L-Malate L-Apple acid L-Malic acid L-2-Hydroxybutanedioic acid Reactome DB_ID: 113544 (S)-malic acid [ChEBI:30797] (S)-malic acid ChEBI CHEBI:30797 Reactome Database ID Release 77 113544 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113544 Reactome R-ALL-113544 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113544.3 COMPOUND C00149 ACTIVATION FH tetramer Reactome DB_ID: 10207530 fh FH Q7SX99 Reactome DB_ID: 10207528 UniProt:Q7SX99 fh UniProt Q7SX99 45 EQUAL 510 EQUAL Reactome Database ID Release 77 10207528 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207528 Reactome R-DRE-70980 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70980.1 4 Reactome Database ID Release 77 10207530 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207530 Reactome R-DRE-451041 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-451041.1 GENE ONTOLOGY GO:0004333 Reactome Database ID Release 77 10207531 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207531 Reactome Database ID Release 77 10207533 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207533 Reactome R-DRE-70982 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70982.1 Mitochondrial fumarate hydratase catalyzes the reversible reaction of fumarate and water to form malate, the seventh step of the TCA cycle (Bourgeron et al. 1994). Unpublished crystallographic data indicate that the protein is a tetramer (PDB 3E04). 8200987 Pubmed 1994 Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency Bourgeron, T Chretien, D Poggi-Bach, J Doonan, S Rabier, D Letouzé, P Munnich, A Rötig, A Landrieu, P Rustin, P J Clin Invest 93:2514-2518 LEFT-TO-RIGHT 4.2.1.2 (S)-Malate <=> Fumarate + H2O This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ACTIVATION Reactome Database ID Release 77 10244022 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10244022 Reactome R-DRE-451033 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-451033.1 Mitochondrial fumarate hydratase catalyzes the reversible reaction of malate to form fumarate and water (Bourgeron et al. 1994). Unpublished crystallographic data indicate that the protein is a tetramer (PDB 3E04). LEFT-TO-RIGHT 1.1.1.37 (S)-Malate + NAD+ <=> Oxaloacetate + NADH + H+ This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ACTIVATION MDH2 dimer Reactome DB_ID: 10207521 mdh2 MDH2 Q7T334 Reactome DB_ID: 10207519 UniProt:Q7T334 mdh2 UniProt Q7T334 25 EQUAL 338 EQUAL Reactome Database ID Release 77 10207519 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207519 Reactome R-DRE-70977 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70977.1 2 Reactome Database ID Release 77 10207521 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207521 Reactome R-DRE-198511 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-198511.1 GENE ONTOLOGY GO:0030060 Reactome Database ID Release 77 10207522 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207522 Reactome Database ID Release 77 10207524 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10207524 Reactome R-DRE-70979 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70979.1 Mitochondrial malate dehydrogenase catalyzes the reversible reaction of malate and NAD+ to form oxaloacetate and NADH + H+ (Luo et al. 2006). This reaction is highly endergonic but is pulled in the direction annotated here when the TCA cycle is operating. Unpublished crystallographic data indicate that the protein is a dimer (PDB 3E04). 16740313 Pubmed 2006 An NADH-tetrazolium-coupled sensitive assay for malate dehydrogenase in mitochondria and crude tissue homogenates Luo, C Wang, X Long, J Liu, J J Biochem Biophys Methods 68:101-11 LEFT-TO-RIGHT 1.1.1.37 Oxaloacetate + NADH + H+ <=> (S)-Malate + NAD+ This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ACTIVATION Reactome Database ID Release 77 10208267 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10208267 Reactome R-DRE-71783 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-71783.1 Mitochondrial malate dehydrogenase catalyzes the reversible reaction of oxaloacetate and NADH + H+ to form malate and NAD+ (Luo et al. 2006). Unpublished crystallographic data indicate that the protein is a dimer (PDB 3E04). 9792106 Pubmed 1998 Aggregation states of mitochondrial malate dehydrogenase Sanchez, SA Hazlett, TL Brunet, JE Jameson, DM Protein Sci 7:2184-2189 LEFT-TO-RIGHT 1.1.1.40 1.1.1.38 4.1.1.112 FAHD1:Zn2+ dimer hydrolyses OA to PYR This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp PYR Pyruvate pyruvic acid 2-Oxopropanoate 2-Oxopropanoic acid Pyroracemic acid Reactome DB_ID: 113557 pyruvate [ChEBI:15361] pyruvate 2-oxopropanoate 2-oxopropanoic acid, ion(1-) ChEBI CHEBI:15361 Reactome Database ID Release 77 113557 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113557 Reactome R-ALL-113557 4 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113557.4 COMPOUND C00022 ACTIVATION FAHD1:Mg2+ dimer Reactome DB_ID: 10316586 FAHD1:Mg2+ Reactome DB_ID: 10316584 Mg2+ magnesium magnesium(2+) Mg++ Reactome DB_ID: 109496 magnesium(2+) [ChEBI:18420] magnesium(2+) ChEBI CHEBI:18420 Reactome Database ID Release 77 109496 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=109496 Reactome R-ALL-109496 3 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-109496.3 COMPOUND C00305 1 fahd1 FAHD1 F1Q6L1 Reactome DB_ID: 10316582 UniProt:F1Q6L1 fahd1 UniProt F1Q6L1 28 EQUAL 224 EQUAL Reactome Database ID Release 77 10316582 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316582 Reactome R-DRE-9012048 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012048.1 1 Reactome Database ID Release 77 10316584 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316584 Reactome R-DRE-9012015 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012015.1 2 Reactome Database ID Release 77 10316586 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316586 Reactome R-DRE-9012057 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012057.1 GENE ONTOLOGY GO:0008948 Reactome Database ID Release 77 10316587 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316587 Reactome Database ID Release 77 10316589 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316589 Reactome R-DRE-9012016 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012016.1 Fumarylacetoacetate hydrolase domain containing protein 1 (FAHD1) (Pircher et al. 2011, 2015, Jansen-Duerr et al. 2016) was identified to display a bi-functional catalytic mechanism (Weiss et al. 2018), being able to hydrolyse acylpyruvates (Pircher et al. 2011) similar to fumarylpyruvate hydrolase NagK of Ralstonia sp. (acetylpyruvate: vmax = 0,135 µmol/min/mg, KM = 4,6 µM), and to cleave oxaloacetate (OAA) via decarboxylation (Pircher et al. 2015) (OAA: vmax = 0,21 µmol/min/mg, KM = 32 µM). The enzyme is of dimeric form (Manjasetty et al. 2004) and uses Mg2+ or Mn2+ as cofactor. It is localized in the mitochondrial matrix (Pircher et al. 2011, Trukhina et al. 2002, Di Berardino et al. 1996). Its identification as ODx (Pircher et al. 2015) renders FAHD1 a possible antagonist to pyruvate carboxylase (PC) at a central position in the TCA cycle(Jansen-Duerr et al. 2016). It is believed that the ability of FAHD1 to decarboxylate OAA provides the basis of its requirement for maintaining healthy mitochondria in certain cells and tissues (Taferner et al. 2015, Petit et al. 2017). However, further studies of this topic are warranted. 21878618 Pubmed 2011 Identification of human fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) as a novel mitochondrial acylpyruvase Pircher, Haymo Straganz, Grit D Ehehalt, Daniela Morrow, Geneviève Tanguay, Robert M Jansen-Dürr, Pidder 生物. Chem. 286:36500-8 25575590 Pubmed 2015 Identification of FAH domain-containing protein 1 (FAHD1) as oxaloacetate decarboxylase Pircher, Haymo von Grafenstein, Susanne Diener, Thomas Metzger, Christina Albertini, Eva Taferner, Andrea Unterluggauer, Hermann Kramer, Christian Liedl, Klaus R Jansen-Dürr, Pidder 生物. Chem. 290:6755-62 28286170 Pubmed 2017 Depletion of oxaloacetate decarboxylase FAHD1 inhibits mitochondrial electron transport and induces cellular senescence in human endothelial cells Petit, Michele Koziel, Rafal Etemad, Solmaz Pircher, Haymo Jansen-Dürr, Pidder Exp. Gerontol. 92:7-12 15551868 Pubmed 2004 X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880 Manjasetty, Babu A Niesen, Frank H Delbrück, Heinrich Götz, Frank Sievert, Volker Büssow, Konrad Behlke, Joachim Heinemann, Udo Biol. Chem. 385:935-42 LEFT-TO-RIGHT 1.1.1.38 1.1.1.39 ME2:Mg2+ tetramer oxidatively decarboxylates MAL to PYR This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ACTIVATION ME2:Mg2+ tetramer Reactome DB_ID: 10316612 ME2:Mg2+ dimer Reactome DB_ID: 10316610 ME2:Mg2+ Reactome DB_ID: 10316608 me2 ME2 A5PN55 Reactome DB_ID: 10316606 UniProt:A5PN55 me2 UniProt A5PN55 19 EQUAL 584 EQUAL Reactome Database ID Release 77 10316606 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316606 Reactome R-DRE-9012080 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012080.1 1 1 Reactome Database ID Release 77 10316608 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316608 Reactome R-DRE-9012271 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012271.1 2 Reactome Database ID Release 77 10316610 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316610 Reactome R-DRE-9012259 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012259.1 2 Reactome Database ID Release 77 10316612 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316612 Reactome R-DRE-9012264 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012264.1 GENE ONTOLOGY GO:0004471 Reactome Database ID Release 77 10316613 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316613 Reactome Database ID Release 77 10316615 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316615 Reactome R-DRE-9012268 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012268.1 One hallmark of cancer is altered cellular metabolism. Malic enzymes (MEs) are a family of homotetrameric enzymes that catalyse the reversible oxidative decarboxylation of L-malate to pyruvate, with a simultaneous reduction of NAD(P)+ to NAD(P)H. As MEs generate NADPH and NADH, they may play dual roles in energy production and reductive biosynthesis. Humans possess three ME isoforms; ME1 is cytosolic and utilises NADP+, ME3 is mitochondrial and can utilise NADP+ and ME2 is mitochondrial and can utililse either NAD+ or NADP+ (Chang & Tong 2003).

Mitochondrial NAD-dependent malic enzyme (ME2, aka m-NAD(P)-ME) oxidatively decarboxylates (s)-malate (MAL) to pyruvate (PYR) and CO2 using NAD+ (or NADP+) as cofactor (Loeber et al. 1991, Tao et al. 2003). ME2 exists as a dimer of dimers and requires a divalent metal such as Mg2+ for catalysis (Chang & Tong 2003, Murugan & Hung 2012). Unlike the other MEs, ME2's enzymatic activity can be allosterically activated by fumarate (FUMA) and inhibited by ATP (Yang et al. 2002). ME2 could play a critical role in cutaneous melanoma progression, the most life-threatening neoplasm of the skin. Targeting ME2 could be a novel approach to inhibiting melanoma cell proliferation and growth (Chang et al. 2015). ME2 has also been demonstrated to be involved in glioblastoma multiforme (GBM) growth, invasion and migration. Inhibition of ME2 could potentially be therapeutic in the treatment of GBM (Cheng et al. 2016). 14596586 Pubmed 2003 Structure and function of malic enzymes, a new class of oxidative decarboxylases Chang, Gu-Gang Tong, L Biochemistry 42:12721-33 23284632 Pubmed 2012 Biophysical characterization of the dimer and tetramer interface interactions of the human cytosolic malic enzyme Murugan, Sujithkumar Hung, Hui-Chih PLoS ONE 7:e50143 27166188 Pubmed 2016 The mechanisms of malic enzyme 2 in the tumorigenesis of human gliomas Cheng, Chiao-Pei Huang, Li-Chun Chang, Yung-Lung Hsieh, Ching-Hsuan Huang, Shih-Ming Hueng, Dueng-Yuan Oncotarget 7:41460-41472 25202825 Pubmed 2015 Human mitochondrial NAD(P)(+)-dependent malic enzyme participates in cutaneous melanoma progression and invasion Chang, Yung-Lung Gao, Hong-Wei Chiang, Chien-Ping Wang, Wei-Ming Huang, Shih-Ming Ku, Chien-Fen Liu, Guang-Yaw Hung, Hui-Chih J. Invest. Dermatol. 135:807-15 1993674 Pubmed 1991 Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli Loeber, G Infante, A A Maurer-Fogy, I Krystek, E Dworkin, M B 生物. Chem. 266:3016-21 12121650 Pubmed 2002 Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate Yang, Zhiru Lanks, Charles W Tong, L Structure 10:951-60 12962632 Pubmed 2003 Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism Tao, Xiao Yang, Zhiru Tong, L Structure 11:1141-50 ACTIVATION Reactome Database ID Release 77 9012256 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9012256 Reactome R-HSA-9012256 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9012256.1 INHIBITION Reactome Database ID Release 77 9012284 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9012284 Reactome R-HSA-9012284 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9012284.1 LEFT-TO-RIGHT 1.1.1.40 ME3:Mg2+ tetramer oxidatively decarboxylates MAL to PYR This event has been computationally inferred from an event that has been demonstrated in another species.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp ACTIVATION ME3:Mg2+ tetramer Reactome DB_ID: 10316642 ME3:Mg2+ dimer Reactome DB_ID: 10316640 ME3:Mg2+ Reactome DB_ID: 10316638 me3 ME3 A4QPA0 Reactome DB_ID: 10316636 UniProt:A4QPA0 me3 UniProt A4QPA0 1 EQUAL 604 EQUAL Reactome Database ID Release 77 10316636 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316636 Reactome R-DRE-9012082 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012082.1 1 1 Reactome Database ID Release 77 10316638 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316638 Reactome R-DRE-9012355 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012355.1 2 Reactome Database ID Release 77 10316640 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316640 Reactome R-DRE-9012350 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012350.1 2 Reactome Database ID Release 77 10316642 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316642 Reactome R-DRE-9012356 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012356.1 GENE ONTOLOGY GO:0004473 Reactome Database ID Release 77 10316643 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316643 Reactome Database ID Release 77 10316645 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10316645 Reactome R-DRE-9012349 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-9012349.1 One hallmark of cancer is altered cellular metabolism. Malic enzymes (MEs) are a family of homotetrameric enzymes that catalyse the reversible oxidative decarboxylation of L-malate to pyruvate, with a simultaneous reduction of NAD(P)+ to NAD(P)H. As MEs generate NADPH and NADH, they may play roles in energy production and reductive biosynthesis. Humans possess three ME isoforms; ME1 is cytosolic and utilises NADP+, ME3 is mitochondrial and can utilise NADP+ and ME2 is mitochondrial and can utililse either NAD+ or NADP+ (Chang & Tong 2003, Murugan & Hung 2012).

NADP-dependent malic enzyme (ME3, aka m-NADP-ME) is a mitochondrial enzyme that oxidatively decarboxylates (s)-malate (MAL) to pyruvate (PYR) and CO2 using NADP+ as cofactor (Loeber et al. 1994). ME1 exists as a dimer of dimers (Murugan & Hung 2012) and a divalent metal such as Mg2+ is essential for catalysis (Chang & Tong 2003). ME3 may play a role in insulin secretion (Hasan et al. 2015) but how it does this in panceratic beta cells has not been established yet. 25594249 Pubmed 2015 Mitochondrial malic enzyme 3 is important for insulin secretion in pancreatic β-cells Hasan, Noaman M Longacre, Melissa J Stoker, Scott W Kendrick, Mindy A MacDonald, Michael J Mol. Endocrinol. 29:396-410 7818469 Pubmed 1994 Purification, cDNA cloning and heterologous expression of the human mitochondrial NADP(+)-dependent malic enzyme Loeber, G Maurer-Fogy, I Schwendenwein, R Biochem. J. 304:687-92 Reactome Database ID Release 77 10321272 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=10321272 Reactome R-DRE-71403 1 Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-71403.1 GENE ONTOLOGY GO:0006099 基因本体术语细胞过程 MI MI:0359 在柠檬酸或三羧酸(TCA)本体le, the acetyl group of acetyl CoA (derived primarily from oxidative decarboxylation of pyruvate, beta-oxidation of long-chain fatty acids, and catabolism of ketone bodies and several amino acids) can be completely oxidized to CO2 in reactions that also yield one high-energy phosphate bond (as GTP or ATP) and four reducing equivalents (three NADH + H+, and one FADH2). The NADH and FADH2 are then oxidized by the electron transport chain to yield nine more high-energy phosphate bonds (as ATP). All reactions of the citric acid cycle take place in the mitochondrion.

Eight canonical reactions mediate the synthesis of citrate from acetyl-CoA and oxaloacetate and the metabolism of citrate to re-form oxaloacetate. Six additional reactions are included here. Three reversible reactions, the interconversions of citrate and isocitrate, of fumarate and malate, and of malate and oxaloacetate are annotated in both their canonical (forward) and reverse directions. The synthesis of succinate from succinyl-CoA can be coupled to the phosphorylation of either GDP (the canonical reaction) or ADP; both reactions are annotated. Two mitochondrial isocitrate dehydrogenase isozymes catalyze the oxidative decarboxylation of isocitrate to form alpha-ketoglutarate (2-oxoglutarate): IDH3 catalyzes the canonical reaction coupled to the reduction of NAD+, while IDH2 catalyzes the same reaction coupled to reduction of NADP+, a reaction whose normal physiological function is unclear. Both reactions are annotated. Finally, a reaction is annotated in which reducing equivalents are transferred from NADPH to NAD+ coupled to proton import across the inner mitochondrial membrane.

The cyclical nature of the reactions responsible for the oxidation of acetate was first suggested by Hans Krebs, from biochemical studies of pigeon breast muscle (Krebs et al. 1938; Krebs and Eggleston 1940). Many of the molecular details of individual reactions were worked out by Ochoa and colleagues, largely through studies of enzymes purified from pig heart (Ochoa 1980). While the human homologues of these enzymes have all been identified, their biochemical characterization has in general been limited and many molecular details of the human reactions are inferred from those worked out in studies of the model systems. 16747180 Pubmed 1940 The oxidation of pyruvate in pigeon breast muscle Krebs, HA Eggleston, LV Biochem J 34:442-459 6773467 Pubmed 1980 The pursuit of a hobby Ochoa, S Annu Rev Biochem 49:1-30 16746585 Pubmed 1938 The formation of citric and alpha-ketoglutaric acids in the mammalian body Krebs, HA Salvin, E Johnson, WA Biochem J 32:113-117