BioPAX pathway converted from "D-glyceraldehyde 3-phosphate + orthophosphate + NAD+ <=> 1,3-bisphospho-D-glycerate + NADH + H+" in the Reactome database.LEFT-TO-RIGHT1.2.1.12D-glyceraldehyde 3-phosphate + orthophosphate + NAD+ <=> 1,3-bisphospho-D-glycerate + NADH + H+Glyceraldehyde 3 phosphate, NAD+, and orthophosphate react to form 1,3 bisphosphoglycerate and NADH + H+Cytosolic glyceraldehyde 3-phosphate dehydrogenase catalyzes the reversible reaction of glyceraldehyde 3-phosphate, orthophosphate, and NAD+ to form NADH + H+ and 1,3-bisphosphoglycerate, the first energy rich intermediate of glycolysis. The biochemical details of this reaction were worked out by C and G Cori and their colleagues (Taylor et al. 1948; Cori et al. 1948).<p>While there are multiple human glyceraldehyde 3-phosphate dehydrogenase-like pseudogenes, there is only one glyceraldehyde 3-phosphate dehydrogenase gene expressed in somatic tissue (Benham and Povey 1989; Heinz and Freimuller 1982; Ercolani et al. 1988), and studies of aged human erythrocytes suggest that variant forms of the enzyme arise as a result of post-translational modifications (Edwards et al. 1976). There is, however, an authentic second isoform of glyceraldehyde 3-phosphate dehydrogenase whose expression is confined to spermatogenic cells of the testis (Welch et al. 2000).GA3P(2R)-2-Hydroxy-3-(phosphonooxy)-propanalD-glyceraldehyde 3-phosphateD-glyceraldehyde 3-phosphate(2-)Reactome DB_ID: 29578cytosolGENE ONTOLOGYGO:0005829D-glyceraldehyde 3-phosphate(2-) [ChEBI:59776]D-glyceraldehyde 3-phosphate(2-)D-glyceraldehyde 3-phosphate(2R)-2-hydroxy-3-oxopropyl phosphateD-glyceraldehyde 3-phosphate dianionChEBICHEBI:59776Reactome Database ID Release 7529578Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29578ReactomeR-ALL-295784Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29578.4Reactomehttp://www.reactome.orgCOMPOUNDC00118additional informationMIMI:0361NADNAD+NAD(+)Nicotinamide adenine dinucleotideDPNDiphosphopyridine nucleotideReactome DB_ID: 29360NAD(1-) [ChEBI:57540]NAD(1-)adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate}NAD(+)NAD anionChEBICHEBI:57540Reactome Database ID Release 7529360Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29360ReactomeR-ALL-293605Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29360.5COMPOUNDC00003PiOrthophosphatehydrogenphosphatePhosphateInorganic PhosphateReactome DB_ID: 29372hydrogenphosphate [ChEBI:43474]hydrogenphosphatehydrogen phosphatephosphate[PO3(OH)](2-)INORGANIC PHOSPHATE GROUPHYDROGENPHOSPHATE IONHPO4(2-)[P(OH)O3](2-)ChEBICHEBI:43474Reactome Database ID Release 7529372Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29372ReactomeR-ALL-293724Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29372.4COMPOUNDC000091,3BPG3-phosphonato-D-glyceroyl phosphate(4-)1,3-Bisphospho-D-glycerate3-phospho-D-glyceroyl dihydrogen phosphate3-Phospho-D-glyceroyl phosphate(R)-2-Hydroxy-3-(phosphonooxy)-1-monoanhydridewith phosphoric propanoic acidReactome DB_ID: 298003-phosphonato-D-glyceroyl phosphate(4-) [ChEBI:57604]3-phosphonato-D-glyceroyl phosphate(4-)3-phosphonato-D-glyceroyl phosphate tetraanion(2R)-2-hydroxy-1-oxopropane-1,3-diyl bis(phosphate)(2R)-3-phospho-glyceroyl phosphateChEBICHEBI:57604Reactome Database ID Release 7529800Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29800ReactomeR-ALL-298005Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29800.5NADHReactome DB_ID: 73473NADH(2-) [ChEBI:57945]NADH(2-)NADH dianionadenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate}NADHChEBICHEBI:57945Reactome Database ID Release 7573473Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=73473ReactomeR-ALL-734734Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-73473.4COMPOUNDC00004H+protonhydronReactome DB_ID: 70106hydron [ChEBI:15378]hydronChEBICHEBI:15378Reactome Database ID Release 7570106Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70106ReactomeR-ALL-701064Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70106.4COMPOUNDC00080ACTIVATIONConverted from EntitySet in ReactomeGAPDH tetramersglyceraldehyde-3-phosphate dehydrogenase tetramerReactome DB_ID: 372871glyceraldehyde-3-phosphate dehydrogenase tetramerReactome DB_ID: 70447GAPDHglyceraldehyde-3-phosphate dehydrogenase monomerglyceraldehyde 3-phosphate dehydrogenase, liverglyceraldehyde 3-phosphate dehydrogenase, muscleG3P2_HUMANG3P1_HUMANGlyceraldehyde 3-phosphate dehydrogenase, liver Reactome DB_ID: 70428UniProt:P04406 GAPDHGAPDHGAPDCDABP0047OK/SW-cl.12FUNCTION Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.ACTIVITY REGULATION Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues.PATHWAY Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.SUBUNIT Homotetramer. Interacts with TPPP; the interaction is direct. Interacts (when S-nitrosylated) with SIAH1; leading to nuclear translocation. Interacts with RILPL1/GOSPEL, leading to prevent the interaction between GAPDH and SIAH1 and prevent nuclear translocation. Interacts with CHP1; the interaction increases the binding of CHP1 with microtubules. Associates with microtubules (By similarity). Interacts with EIF1AD, USP25, PRKCI and WARS1. Interacts with phosphorylated RPL13A; inhibited by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity.DOMAIN The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.PTM S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus (By similarity). S-nitrosylation of Cys-247 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity.PTM ISGylated.PTM Sulfhydration at Cys-152 increases catalytic activity.PTM Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation. Such aggregates can be observed in vivo in the affected tissues of patients with Alzheimer disease or alcoholic liver cirrhosis, or in cell cultures during necrosis. Oxidation at Met-46 may play a pivotal role in the formation of these insoluble structures. This modification has been detected in vitro following treatment with free radical donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide. It has been proposed to destabilize nearby residues, increasing the likelihood of secondary oxidative damages, including oxidation of Tyr-45 and Met-105. This cascade of oxidations may augment GAPDH misfolding, leading to intermolecular disulfide cross-linking and aggregation.PTM Succination of Cys-152 and Cys-247 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits glyceraldehyde-3-phosphate dehydrogenase activity. Fumarate concentration as well as succination of cysteine residues in GAPDH is significantly increased in muscle of diabetic mammals. It was proposed that the S-(2-succinyl)cysteine chemical modification may be a useful biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications.SIMILARITY Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.Homo sapiensNCBI Taxonomy9606UniProtP044062EQUAL335EQUALReactome Database ID Release 7570428Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70428ReactomeR-HSA-704281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70428.14Reactome Database ID Release 7570447Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70447ReactomeR-HSA-704471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70447.1glyceraldehyde-3-phosphate dehydrogenase, testis-specific, tetramerReactome DB_ID: 372869GAPDHSglyceraldehyde-3-phosphate dehydrogenase, testis-specific, monomerReactome DB_ID: 372873UniProt:O14556 GAPDHSGAPDHSGAPD2GAPDH2GAPDSHSD-35HSD35FUNCTION May play an important role in regulating the switch between different pathways for energy production during spermiogenesis and in the spermatozoon. Required for sperm motility and male fertility (By similarity).PATHWAY Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.SUBUNIT Homotetramer. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation.TISSUE SPECIFICITY Testis specific.DOMAIN The testis-specific N-terminal extension mediates tight association with the cytoskeletal fibrous sheath of the spermatozoa flagellum, possibly via interchain disulfide-bonding of Cys-21 with sheath components.SIMILARITY Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.UniProtO145561EQUAL408EQUALReactome Database ID Release 75372873Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=372873ReactomeR-HSA-3728731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-372873.14Reactome Database ID Release 75372869Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=372869ReactomeR-HSA-3728691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-372869.1Reactome Database ID Release 75372871Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=372871ReactomeR-HSA-3728712Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-372871.2GENE ONTOLOGYGO:0004365gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7570448Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70448Reactome Database ID Release 7570449Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70449ReactomeR-HSA-704493Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70449.310714828Pubmed2000Human glyceraldehyde 3-phosphate dehydrogenase-2 gene is expressed specifically in spermatogenic cells.Welch, JEBrown, PLO'Brien, DAMagyar, PLBunch, DOMori, CEddy, EMJ Androl 21:328-3818910716Pubmed1948Crystalline D-glyceraldehyde-3-phosphate dehydrogenase from rabbit muscleCori, GTSlein, MWCori, Carl FJ Biol Chem 173:605-6183170585Pubmed1988Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase geneErcolani, LFlorence, BDenaro, MAlexander, MJ Biol Chem 263:15335-417144574Pubmed1983Glyceraldehyde-3-phosphate dehydrogenase from human tissues.Heinz, FFreimüller, BMethods Enzymol 89:301-52793178Pubmed1989Members of the human glyceraldehyde-3-phosphate dehydrogenase-related gene family map to dispersed chromosomal locations.Benham, FJPovey, SGenomics 5:209-14183598Pubmed1976Isozymes of glyceraldehyde-3-phosphate dehydrogenase in man and other mammals.Edwards, YHClark, PHarris, HAnn Hum Genet 40:67-7718910717Pubmed1948The prosthetic group of crystalline d-glyceraldehyde-3-phosphate dehydrogenaseTAYLOR, J FVELICK, S FJ. Biol. Chem. 173:619-26