The oxidative branch of the pentose phosphate pathway, reactions 1-3, generates NADPH and pentose 5-phosphate. The non-oxidative branch of the pathway, reactions 4-8, converts pentose 5-phosphate to other sugars.

The overall pathway can operate to generate only NADPH (glucose 6-phosphate is converted to pentose 5-phosphates, which are directed to the synthesis of fructose 6-phosphate and glyceraldehyde 3-phosphate, which in turn are converted back to glucose 6-phosphate). The reactions of the non-oxidative branch can operate to generate net amounts of ribose 5-phosphate with no production of NADPH. Net flux through this network of reactions appears to depend on the metabolic state of the cell and the nature of the biosynthetic reactions underway (Casazza and Veech 1987).

G6PD, the enzyme that catalyzes the first reaction of the pathway, is more extensively mutated in human populations than any other enzyme, pehaps because these mutant alleles confer malaria resistance (Luzzatto and Afolayan 1968). Mutations affecting other parts of the pathway are rare, though several have been described and studies of their effects have contributed to our understanding of the normal flux of metabolites through this network of reactions (Wamelink et al. 2008). Authored: 2003-02-15 00:00:00 1.1.1.49 alpha-D-glucose 6-phosphate + NADP+ => D-glucono-1,5-lactone 6-phosphate + NADPH + H+ alpha-D-glucose 6-phosphate + NADP+ => D-glucono-1,5-lactone 6-phosphate + NADPH + H+ Cytosolic glucose-6-phosphate dehydrogenase (G6PD) catalyzes the reaction of glucose 6-phosphate and NADP+ to form D-glucono-1,5-lactone 6-phosphate and NADPH + H+. This constitutes the first committed step of the pentose phosphate pathway and it is critical to the maintenance of NAPDH pool and redox homeostasis. For this reason, anti-cancer therapies are making this step as a prominent target in cancer therapy (Zhang et al. 2014). The reaction is inhibited by high ADP/AMP concentration, and by high NAPDH concentration. Biochemical studies indicate that both G6PD dimers and tetramers are catalytically active and present under physiological conditions in vivo (Au et al. 2000). Mutations that reduce the catalytic efficiency of G6PD are remarkably common in human populations; these appear to have a protective effect against malaria (e.g., Luzzatto and Afolayan 1968). Authored: D'Eustachio, P, 2003-06-25 00:00:00 Reviewed: Inga, Alberto, 2016-02-04 Reviewed: Zaccara, Sara, 2016-02-04 Edited: D'Eustachio, P, 2010-01-24 Reactome DB_ID: 29366 1 cytosol GO 0005829 NADP(+) [ChEBI:18009] NADP(+) Reactome //www.joaskin.com ChEBI 18009 Reactome DB_ID: 30537 1 alpha-D-glucose 6-phosphate(2-) [ChEBI:58225] alpha-D-glucose 6-phosphate(2-) alpha-D-glucose 6-phosphate dianion alpha-D-glucopyranose 6-phosphate 6-O-phosphonato-alpha-D-glucopyranose alpha-D-glucose 6-phosphate ChEBI 58225 Reactome DB_ID: 29364 1 NADPH [ChEBI:16474] NADPH TPNH ChEBI 16474 Reactome DB_ID: 31467 1 6-O-phosphono-D-glucono-1,5-lactone [ChEBI:16938] 6-O-phosphono-D-glucono-1,5-lactone ChEBI 16938 Reactome DB_ID: 70106 1 hydron [ChEBI:15378] hydron ChEBI 15378 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 464971 G6PD dimer and tetramer [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0004345 GO molecular function Reactome Database ID Release 77 70374 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70374 Reactome Database ID Release 77 70377 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70377 Reactome R-HSA-70377 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70377.3 5666113 Pubmed 1968 Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variants Luzzatto, L Afolayan, A J Clin Invest 47:1833-42 24066844 Pubmed 2014 Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancer Zhang, Chunhua Zhang, Zheng Zhu, Yuechun Qin, Suofu Anticancer Agents Med Chem 14:280-9 10745013 Pubmed 2000 Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiency Au, SW Gover, S Lam, VM Adams, MJ Structure 8:293-303 3.1.1.31 D-glucono-1,5-lactone 6-phosphate + H2O => 6-phospho-D-gluconate D-glucono-1,5-lactone 6-phosphate + H2O => 6-phospho-D-gluconate Cytosolic 6-phosphogluconolactonase (PGLS) catalyzes the hydrolysis of D-glucono-1,5-lactone 6-phosphate to form 6-phospho-D-gluconate (Beutler and Kuhl 1985; Collard et al. 1999). Reactome DB_ID: 31467 1 Reactome DB_ID: 29356 1 water [ChEBI:15377] water ChEBI 15377 Reactome DB_ID: 29996 1 6-phospho-D-gluconate [ChEBI:16863] 6-phospho-D-gluconate ChEBI 16863 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71294 UniProt:O95336 PGLS PGLS PGLS 函数6-phosphogluconolactone的水解6-phosphogluconate.PATHWAY Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 2/3.SIMILARITY Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily. Homo sapiens NCBI Taxonomy 9606 UniProt O95336 Chain Coordinates 2 EQUAL 258 EQUAL GO 0017057 GO molecular function Reactome Database ID Release 77 71295 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71295 Reactome Database ID Release 77 71296 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71296 Reactome R-HSA-71296 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71296.3 3932573 Pubmed 1985 Limiting role of 6-phosphogluconolactonase in erythrocyte hexose monophosphate pathway metabolism Beutler, Ernest Kuhl, W J Lab Clin Med 106:573-7 10518023 Pubmed 1999 Identification of the cDNA encoding human 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway(1) Collard, F Collet, JF Gerin, I Veiga-da-Cunha, M Van Schaftingen, Emile FEBS Lett 459:223-6 1.1.1.44 6-phospho-D-gluconate + NADP+ => D-ribulose 5-phosphate + CO2 + NADPH + H+ 6-phospho-D-gluconate + NADP+ => D-ribulose 5-phosphate + CO2 + NADPH + H+ Cytosolic phosphogluconate dehydrogenase (PGD) catalyzes the reaction of 6-phospho-D-gluconate and NADP+ to form D-ribulose 5-phosphate, CO2, and NADPH + H+ (Beutler and Kuhl 1985; Rippa et al. 1998). The PGD enzyme is dimeric (Dallocchio et al. 1985). Reactome DB_ID: 29366 1 Reactome DB_ID: 29996 1 Reactome DB_ID: 29364 1 Reactome DB_ID: 113528 1 carbon dioxide [ChEBI:16526] carbon dioxide ChEBI 16526 Reactome DB_ID: 29732 1 D-ribulose 5-phosphate [ChEBI:17363] D-ribulose 5-phosphate ChEBI 17363 Reactome DB_ID: 70106 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 467365 PGD dimer [cytosol] PGD dimer Reactome DB_ID: 71297 2 UniProt:P52209 PGD PGD PGD PGDH FUNCTION Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.PATHWAY Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 3/3.SUBUNIT Homodimer.SIMILARITY Belongs to the 6-phosphogluconate dehydrogenase family. UniProt P52209 2 EQUAL 483 EQUAL Reactome Database ID Release 77 467365 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=467365 Reactome R-HSA-467365 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-467365.1 GO 0004616 GO molecular function Reactome Database ID Release 77 71298 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71298 Reactome Database ID Release 77 71299 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71299 Reactome R-HSA-71299 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71299.3 9920387 Pubmed 1998 6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species Rippa, M Giovannini, PP Barrett, MP Dallocchio, F Hanau, S Biochim Biophys Acta 1429:83-92 3994686 Pubmed 1985 Half-site reactivity in 6-phosphogluconate dehydrogenase from human erythrocytes Dallocchio, F Matteuzzi, M Bellini, T Biochem J 227:305-10 2.7.1.15 RBKS phosphorylates ribose to R5P RBKS phosphorylates ribose to R5P In order for D-ribose to be incorporated into ATP or other high energy phosphorylated derivatives, ribose must first be converted into ribose-5-phosphate (R5P), which can then be used either for sythesis of nucleotides, histidine, and tryptophan, or as a component of the pentose phosphate pathway. Cytosolic ribokinase (RBKS) catalyses this reaction in the presence of ATP (Park et al. 2007). Other pentoses and simple sugars were either not or poorly phosphorylated by RBKS. RBKS belongs to the PfkB family of carbohydrate kinases which includes adenosine kinase (AK) and fructokinase. RBKS shares high structural similarity to AK and its catalytic mechanism is very similar to AK (Park & Gupta 2008). Authored: Jassal, Bijay, 2017-01-13 Reviewed: D'Eustachio, Peter, 2017-01-30 Edited: Jassal, Bijay, 2017-01-13 Reactome DB_ID: 113592 1 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 8955853 1 D-ribofuranose [ChEBI:47013] D-ribofuranose ChEBI 47013 Reactome DB_ID: 73578 1 D-ribose 5-phosphate [ChEBI:78679] D-ribose 5-phosphate ChEBI 78679 Reactome DB_ID: 29370 1 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 8955847 UniProt:Q9H477 RBKS RBKS RBKS RBSK FUNCTION Catalyzes the phosphorylation of ribose at O-5 in a reaction requiring ATP and magnesium. The resulting D-ribose-5-phosphate can then be used either for sythesis of nucleotides, histidine, and tryptophan, or as a component of the pentose phosphate pathway.ACTIVITY REGULATION Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity (By similarity). Competitively inhibited by phosphonoacetic acid, etidronate, 2-carboxethylphosphonic acid, N-(phosphonomethyl)glycine, N-(phosphonomethyl)iminodiacetic acid and clodronate (PubMed:17585908).PATHWAY Carbohydrate metabolism; D-ribose degradation; D-ribose 5-phosphate from beta-D-ribopyranose: step 2/2.SUBUNIT Homodimer.SIMILARITY Belongs to the carbohydrate kinase PfkB family. Ribokinase subfamily. UniProt Q9H477 1 EQUAL 322 EQUAL GO 0004747 GO molecular function Reactome Database ID Release 77 8955849 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8955849 Reactome Database ID Release 77 8955844 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8955844 Reactome R-HSA-8955844 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8955844.1 17585908 Pubmed 2007 Identification and characterization of human ribokinase and comparison of its properties with E. coli ribokinase and human adenosine kinase Park, Jae van Koeverden, Paul Singh, Bhag Gupta, Radhey S FEBS Lett. 581:3211-6 18560757 Pubmed 2008 Adenosine kinase and ribokinase--the RK family of proteins Park, J Gupta, R S Cell. Mol. Life Sci. 65:2875-96 5.3.1.6 ribose 5-phosphate <=> D-ribulose 5-phosphate ribose 5-phosphate <=> D-ribulose 5-phosphate RPIA异构化核糖5-phosphate D-ribulose 5-phosphate The reversible interconversion of ribose 5-phosphate and ribulose 5-phosphate is catalyzed by cytosolic ribose 5-phosphate isomerase (Huck et al. 2004). Edited: D'Eustachio, P, 2006-04-05 13:59:09 Reactome DB_ID: 73578 1 Reactome DB_ID: 29732 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71304 UniProt:P49247 RPIA RPIA RPIA RPI PATHWAY Carbohydrate degradation; pentose phosphate pathway; D-ribose 5-phosphate from D-ribulose 5-phosphate (non-oxidative stage): step 1/1.SIMILARITY Belongs to the ribose 5-phosphate isomerase family. UniProt P49247 1 EQUAL 311 EQUAL GO 0004751 GO molecular function Reactome Database ID Release 77 71305 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71305 Reactome Database ID Release 77 177784 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=177784 Reactome R-HSA-177784 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-177784.3 14988808 Pubmed 2004 Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy Huck, Jojanneke H J Verhoeven, Nanda M Struys, Eduard A Salomons, Gajja S Jakobs, Cornelis van der Knaap, Marjo S Am J Hum Genet 74:745-51 5.3.1.6 D-ribulose 5-phosphate <=> ribose 5-phosphate D-ribulose 5-phosphate <=> ribose 5-phosphate RPIA isomerizes D-ribulose 5-phosphate to ribose 5-phosphate The reversible interconversion of ribulose 5-phosphate and ribose 5-phosphate is catalyzed by cytosolic ribose 5-phosphate isomerase (Huck et al. 2004). Edited: D'Eustachio, P, 2006-04-05 13:59:09 Reactome DB_ID: 29732 1 Reactome DB_ID: 73578 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71304 1 EQUAL 311 EQUAL Reactome Database ID Release 77 71306 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71306 Reactome R-HSA-71306 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71306.3 5.1.3.1 RPE dimers isomerise RU5P to XY5P RPE dimers isomerise RU5P to XY5P D-ribulose 5-phosphate <=> xylulose 5-phosphate Cytosolic ribulose-5-phosphate-3-epimerase (RPE), using Fe2+ as cofactor, catalyzes the reversible interconversion of D-ribulose 5-phosphate (RU5P) and D-xylulose 5-phosphate (XY5P) (Bose & Pilz 1985, Liang et al. 2011). The electrophoretic properties of RPE activity detected in extracts of mouse-human somatic cell hybrids suggest that the active form of the enzyme is a homodimer (Spencer & Hopkinson 1980). Ribulose-phosphate 3-epimerase-like protein 1 (RPEL1), based on sequence similarity, is suggested to function as RPE. Edited: Jassal, Bijay, 2017-01-25 Reactome DB_ID: 29732 1 Reactome DB_ID: 29790 1 D-xylulose 5-phosphate(2-) [ChEBI:57737] D-xylulose 5-phosphate(2-) D-xylulose 5-phosphate D-xylulose 5-phosphate dianion 5-O-phosphonato-D-xylulose 5-O-phosphonato-D-threo-pentos-2-ulose ChEBI 57737 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 8957329 RPE:Fe2+ dimers [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0004750 GO molecular function Reactome Database ID Release 77 71302 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71302 Reactome Database ID Release 77 71303 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71303 Reactome R-HSA-71303 4 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71303.4 7396409 Pubmed 1980 Biochemical genetics of the pentose phosphate cycle: human ribose 5-phosphate isomerase (RPI) and ribulose 5-phosphate 3-epimerase (RPE) Spencer, N Hopkinson, DA Ann Hum Genet 43:335-42 20923965 Pubmed 2011 Conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate: new insights from structural and biochemical studies on human RPE Liang, Wenguang Ouyang, Songying Shaw, Neil Joachimiak, Andrzej Zhang, Rongguang Liu, Zhi-Jie FASEB J. 25:497-504 2581946 Pubmed 1985 Phosphoribosylpyrophosphate synthesis from glucose decreases during amino acid starvation of human lymphoblasts Boss, GR Pilz, RB J Biol Chem 260:6054-9 5.1.3.1 xylulose 5-phosphate <=> D-ribulose 5-phosphate xylulose 5-phosphate <=> D-ribulose 5-phosphate Cytosolic ribulose-5-phosphate-3-epimerase (RPE) catalyzes the reversible interconversion of D-xylulose 5-phosphate and D-ribulose 5-phosphate (Bose and 1985). The electrophoretic properties of RPE activity detected in extracts of mouse-human somatic cell hybrids suggest that the active form of the enzyme is a homodimer (Spencer and Hopkinson 1980). Reactome DB_ID: 29790 1 Reactome DB_ID: 29732 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 8957329 Reactome Database ID Release 77 199803 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=199803 Reactome R-HSA-199803 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-199803.3 2.2.1.1 ribose 5-phosphate + xylulose 5-phosphate <=> sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate ribose 5-phosphate + xylulose 5-phosphate <=> sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate Cytosolic transketolase (TKT) catalyzes the reversible reaction of D-xylulose 5-phosphate and D-ribose 5-phosphate to form D-glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate. The active transketolase enzyme is a homodimer with one molecule of thiamine pyrophosphate and magnesium bound to each monomer (Wang et al. 1997). Reactome DB_ID: 29790 1 Reactome DB_ID: 73578 1 Reactome DB_ID: 29578 1 D-glyceraldehyde 3-phosphate(2-) [ChEBI:59776] D-glyceraldehyde 3-phosphate(2-) D-glyceraldehyde 3-phosphate (2R)-2-hydroxy-3-oxopropyl phosphate D-glyceraldehyde 3-phosphate dianion ChEBI 59776 Reactome DB_ID: 29882 1 sedoheptulose 7-phosphate [ChEBI:15721] sedoheptulose 7-phosphate ChEBI 15721 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71322 TKT dimer [cytosol] TKT dimer transketolase dimer Reactome DB_ID: 71321 2 UniProt:P29401 TKT TKT TKT FUNCTION Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.SUBUNIT Homodimer.SIMILARITY Belongs to the transketolase family. UniProt P29401 1 EQUAL 623 EQUAL Reactome DB_ID: 29480 2 thiamine(1+) diphosphate(3-) [ChEBI:58937] thiamine(1+) diphosphate(3-) thiamine diphosphate thiamine diphosphate dianion thiamine diphosphate(2-) ChEBI 58937 Reactome DB_ID: 29926 2 magnesium(2+) [ChEBI:18420] magnesium(2+) ChEBI 18420 Reactome Database ID Release 77 71322 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71322 Reactome R-HSA-71322 2 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71322.2 GO 0004802 GO molecular function Reactome Database ID Release 77 71323 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71323 Reactome Database ID Release 77 71324 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71324 Reactome R-HSA-71324 4 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71324.4 9357955 Pubmed 1997 Aspartate 155 of human transketolase is essential for thiamine diphosphate-magnesium binding, and cofactor binding is required for dimer formation Wang, JJ Martin, PR Singleton, CK Biochim Biophys Acta 1341:165-72 2.2.1.1 D-glyceraldehyde 3-phosphate + sedoheptulose 7-phosphate<=> xylulose 5-phosphate+ribose 5-phosphate D-glyceraldehyde 3-phosphate + sedoheptulose 7-phosphate<=> xylulose 5-phosphate+ribose 5-phosphate Cytosolic transketolase (TKT) catalyzes the reversible reaction of D-glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate to form D-xylulose 5-phosphate and D-ribose 5-phosphate. The active transketolase enzyme is a homodimer with one molecule of thiamine pyrophosphate and magnesium bound to each monomer (Wang et al. 1997). Reactome DB_ID: 29578 1 Reactome DB_ID: 29882 1 Reactome DB_ID: 29790 1 Reactome DB_ID: 73578 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71322 Reactome Database ID Release 77 163741 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=163741 Reactome R-HSA-163741 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-163741.3 2.2.1.2 sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate <=> D-erythrose 4-phosphate + D-fructose 6-phosphate sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate <=> D-erythrose 4-phosphate + D-fructose 6-phosphate TALDO1 transforms sedoheptulose 7-phosphate and GA3P to Fru(6)P and E4P Dimeric cytosolic transaldolase (TALDO1) catalyzes the reversible reaction of D-glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate to form D-erythrose 4-phosphate and D-fructose 6-phosphate. Protein expressed from the cloned gene has been characterized biochemically and crystallographically (Banki et al. 1994; Thorell et al. 2000) and transaldolase deficiency in a patient has been correlated with a mutation in the TALDO1 gene (Verhoeven et al. 2001). Reactome DB_ID: 29578 1 Reactome DB_ID: 29882 1 Reactome DB_ID: 29878 1 D-erythrose 4-phosphate(2-) [ChEBI:16897] D-erythrose 4-phosphate(2-) ChEBI 16897 Reactome DB_ID: 29512 1 beta-D-fructofuranose 6-phosphate(2-) [ChEBI:57634] beta-D-fructofuranose 6-phosphate(2-) 6-O-phosphonato-beta-D-fructofuranose beta-D-fructofuranose 6-phosphate dianion ChEBI 57634 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 5659970 TALDO1 dimer [cytosol] TALDO1 dimer Reactome DB_ID: 71325 2 UniProt:P37837 TALDO1 TALDO1 TALDO TALDOR TALDO1 TAL FUNCTION Transaldolase is important for the balance of metabolites in the pentose-phosphate pathway.PATHWAY Carbohydrate degradation; pentose phosphate pathway; D-glyceraldehyde 3-phosphate and beta-D-fructose 6-phosphate from D-ribose 5-phosphate and D-xylulose 5-phosphate (non-oxidative stage): step 2/3.SUBUNIT Homodimer.SIMILARITY Belongs to the transaldolase family. Type 1 subfamily. UniProt P37837 1 EQUAL 337 EQUAL Reactome Database ID Release 77 5659970 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=5659970 Reactome R-HSA-5659970 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5659970.1 GO 0004801 GO molecular function Reactome Database ID Release 77 71333 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71333 Reactome Database ID Release 77 71334 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71334 Reactome R-HSA-71334 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71334.3 8300619 Pubmed 1994 Cloning and expression of the human gene for transaldolase. A novel highly repetitive element constitutes an integral part of the coding sequence Banki, Katalin Halladay, D Perl, Andras J Biol Chem 269:2847-51 10869557 Pubmed 2000 The three-dimensional structure of human transaldolase Thorell, Stina Gergely, Peter Banki, Katalin Perl, Andras Schneider, Gunter FEBS Lett. 475:205-8 11283793 Pubmed 2001 Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway. Verhoeven, Nanda M Huck, Jojanneke H J Roos, Birthe Struys, Eduard A Salomons, Gajja S Douwes, Adriaan C van der Knaap, Marjo S Jakobs, Cornelis Am J Hum Genet 68:1086-92 2.2.1.2 D-fructose 6-phosphate + D-erythrose 4-phosphate <=> sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate D-fructose 6-phosphate + D-erythrose 4-phosphate <=> sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate TALDO1 transforms Fru(6)P and E4P to sedoheptulose 7-phosphate and GA3P Dimeric cytosolic transaldolase (TALDO1) catalyzes the reversible reaction of D-erythrose 4-phosphate and D-fructose 6-phosphate to form D-glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate. Protein expressed from the cloned gene has been characterized biochemically and crystallographically (Banki et al. 1994; Thorell et al. 2000) and transaldolase deficiency in a patient has been correlated with a mutation in the TALDO1 gene (Verhoeven et al. 2001). Reactome DB_ID: 29878 1 Reactome DB_ID: 29512 1 Reactome DB_ID: 29578 1 Reactome DB_ID: 29882 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 5659970 Reactome Database ID Release 77 163764 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=163764 Reactome R-HSA-163764 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-163764.3 2.2.1.1 xylulose 5-phosphate + D-erythrose 4-phosphate <=> D-glyceraldehyde 3-phosphate + D-fructose 6-phosphate xylulose 5-phosphate + D-erythrose 4-phosphate <=> D-glyceraldehyde 3-phosphate + D-fructose 6-phosphate Cytosolic transketolase (TKT) catalyzes the reaction of D-erythrose 4-phosphate and D-xylulose 5-phosphate to form D-glyceraldehyde 3-phosphate and D-fructose 6-phosphate. The active transketolase enzyme is a homodimer with one molecule of thiamine pyrophosphate and magnesium bound to each monomer (Wang et al. 1997). Reactome DB_ID: 29878 1 Reactome DB_ID: 29790 1 Reactome DB_ID: 29578 1 Reactome DB_ID: 29512 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71322 Reactome Database ID Release 77 71335 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71335 Reactome R-HSA-71335 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71335.3 2.2.1.1 D-glyceraldehyde 3-phosphate + D-fructose 6-phosphate <=> xylulose 5-phosphate + D-erythrose 4-phosphate D-glyceraldehyde 3-phosphate + D-fructose 6-phosphate <=> xylulose 5-phosphate + D-erythrose 4-phosphate Cytosolic transketolase (TKT) catalyzes the reaction of D-glyceraldehyde 3-phosphate and D-fructose 6-phosphate to form D-erythrose 4-phosphate and D-xylulose 5-phosphate. The active transketolase enzyme is a homodimer with one molecule of thiamine pyrophosphate and magnesium bound to each monomer (Wang et al. 1997). Reactome DB_ID: 29578 1 Reactome DB_ID: 29512 1 Reactome DB_ID: 29878 1 Reactome DB_ID: 29790 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 71322 Reactome Database ID Release 77 163751 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=163751 Reactome R-HSA-163751 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-163751.3 5.4.2.7 PGM2:Mg2+ isomerises R1P to R5P PGM2:Mg2+ isomerises R1P to R5P 核苷分解产品ribose-1-phosphate (R1P) can be used to produce energy during oxidative or mitochondrial stress to minimize or delay stress-induced damage. Two steps connect this nucleoside breakdown product to central carbon metabolism in mammals. In the first step, R1P is isomerised to the corresponding 5-phosphopentose, R5P, mediated by phosphoglucomutase-2 (PGM2). PGM2 is a cytosolic, M2+-dependent enzyme that acts ten times better as a phosphopentomutase (both on R1P and dR1P) than as a phosphoglucomutase (on glucose-1-phosphate) (Maliekal et al. 2007). Authored: Jassal, Bijay, 2015-07-13 Reviewed: D'Eustachio, Peter, 2015-09-14 Edited: Jassal, Bijay, 2015-07-13 Reactome DB_ID: 112016 1 D-ribose 1-phosphate [ChEBI:35425] D-ribose 1-phosphate ChEBI 35425 Reactome DB_ID: 73578 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 453137 PGM2:Mg2+ [cytosol] PGM2:Mg2+ Reactome DB_ID: 29926 1 Reactome DB_ID: 453136 1 UniProt:Q96G03 PGM2 PGM2 MSTP006 PGM2 催化nucleosid的转换函数e breakdown products ribose-1-phosphate and deoxyribose-1-phosphate to the corresponding 5-phosphopentoses. May also catalyze the interconversion of glucose-1-phosphate and glucose-6-phosphate. Has low glucose 1,6-bisphosphate synthase activity.PATHWAY Carbohydrate degradation; 2-deoxy-D-ribose 1-phosphate degradation; D-glyceraldehyde 3-phosphate and acetaldehyde from 2-deoxy-alpha-D-ribose 1-phosphate: step 1/2.SIMILARITY Belongs to the phosphohexose mutase family. UniProt Q96G03 2 EQUAL 612 EQUAL Reactome Database ID Release 77 453137 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=453137 Reactome R-HSA-453137 2 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-453137.2 GO 0008973 GO molecular function Reactome Database ID Release 77 6787332 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=6787332 Reactome Database ID Release 77 6787329 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=6787329 Reactome R-HSA-6787329 2 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6787329.2 17804405 Pubmed 2007 Molecular identification of mammalian phosphopentomutase and glucose-1,6-bisphosphate synthase, two members of the alpha-D-phosphohexomutase family Maliekal, P Sokolova, T Vertommen, Dieter Veiga-da-Cunha, M Van Schaftingen, Emile J Biol Chem 282:31844-51 5.4.2.7 PGM2:Mg2+ isomerises dR1P to dR5P PGM2:Mg2+ isomerises dR1P to dR5P 核苷分解产品deoxyribose-1-phosphate (dR1P) can be used to produce energy during oxidative or mitochondrial stress to minimize or delay stress-induced damage. Two steps connect this nucleoside breakdown product to central carbon metabolism in mammals. In the first step, dR1P is isomerised to the corresponding 5-phosphopentose, dR5P, mediated by phosphoglucomutase-2 (PGM2). PGM2 is a cytosolic, M2+-dependent enzyme that acts ten times better as a phosphopentomutase (both on R1P and dR1P) than as a phosphoglucomutase (on glucose-1-phosphate) (Maliekal et al. 2007). Authored: Jassal, Bijay, 2015-07-13 Reviewed: D'Eustachio, Peter, 2015-09-14 Edited: Jassal, Bijay, 2015-07-13 Reactome DB_ID: 6787326 1 2-deoxy-alpha-D-ribose 1-phosphate [ChEBI:11563] 2-deoxy-alpha-D-ribose 1-phosphate 2-deoxy-1-O-phosphono-alpha-D-erythro-pentofuranose ChEBI 11563 Reactome DB_ID: 6787328 1 2-deoxy-D-ribose 5-phosphate [ChEBI:16132] 2-deoxy-D-ribose 5-phosphate ChEBI 16132 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 453137 Reactome Database ID Release 77 8982667 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8982667 Reactome R-HSA-8982667 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8982667.1 4.1.2.4 DERA cleaves dR5P to GA3P and CH3CHO DERA cleaves dR5P to GA3P and CH3CHO The nucleoside breakdown products ribose-1-phosphate (R1P) and deoxyribose-1-phosphate (dR1P) can be used to produce energy during oxidative or mitochondrial stress to minimize or delay stress-induced damage. Two steps connect these nucleoside breakdown products to central carbon metabolism in mammals. In the second step, deoxy-ribose5-phosphate (dR5P) is cleaved to glyceraldehyde-3-phosphate (GA3P, an intermediate in glycolysis) and acetaldehyde (CH3CHO) by deoxyribose-phosphate aldolase (DERA) (Salleron et al. 2014). Authored: Jassal, Bijay, 2015-07-13 Reviewed: D'Eustachio, Peter, 2015-09-14 Edited: Jassal, Bijay, 2015-07-13 Reactome DB_ID: 6787328 1 Reactome DB_ID: 29578 1 Reactome DB_ID: 29510 1 acetaldehyde [ChEBI:15343] acetaldehyde ChEBI 15343 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 6787324 UniProt:Q9Y315 DERA DERA CGI-26 DERA FUNCTION Catalyzes a reversible aldol reaction between acetaldehyde and D-glyceraldehyde 3-phosphate to generate 2-deoxy-D-ribose 5-phosphate. Participates in stress granule (SG) assembly. May allow ATP production from extracellular deoxyinosine in conditions of energy deprivation.PATHWAY Carbohydrate degradation; 2-deoxy-D-ribose 1-phosphate degradation; D-glyceraldehyde 3-phosphate and acetaldehyde from 2-deoxy-alpha-D-ribose 1-phosphate: step 2/2.SUBUNIT Interacts with YBX1.TISSUE SPECIFICITY Mainly expressed in liver, lung and colon.SIMILARITY Belongs to the DeoC/FbaB aldolase family. DeoC type 2 subfamily. UniProt Q9Y315 1 EQUAL 318 EQUAL GO 0004139 GO molecular function Reactome Database ID Release 77 6787320 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=6787320 Reactome Database ID Release 77 6787321 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=6787321 Reactome R-HSA-6787321 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6787321.1 25229427 Pubmed 2014 DERA is the human deoxyribose phosphate aldolase and is involved in stress response Salleron, Lisa Magistrelli, G Mary, Camille Fischer, Nicolas Bairoch, Amos Lane, Lydie Biochim. Biophys. Acta 1843:2913-25 2.7.1.14 SHPK phosphorylates Sedo to Sedo7P SHPK phosphorylates Sedo to Sedo7P Cytosolic sedoheptulokinase (SHPK aka CARKL) catalyses an orphan reaction in the pentose phosphate pathway and is a novel regulator of glycolytic energy flux which is critical for macrophage activation (Haschemi et al. 2012). The most common mutation in the nephropathic cystinosis (CTNS) gene is a homozygous 57-kb deletion that also includes the adjacent gene SHPK. In nephropathic cystinosis patients, defects in SHPK can cause urinary accumulation of sedoheptulose and erythritol (Wamelink et al. 2008, Kardon et al. 2008). Authored: Jassal, Bijay, 2017-01-30 Reviewed: D'Eustachio, Peter, 2017-02-06 Edited: Jassal, Bijay, 2017-01-30 Reactome DB_ID: 8959707 1 sedoheptulose [ChEBI:16802] sedoheptulose ChEBI 16802 Reactome DB_ID: 113592 1 Reactome DB_ID: 29882 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 70106 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 8959710 UniProt:Q9UHJ6 SHPK SHPK SHPK CARKL FUNCTION Acts as a modulator of macrophage activation through control of glucose metabolism.TISSUE SPECIFICITY Strongly expressed in liver, kidney and pancreas. Expressed at lower levels in placenta and heart. Very weakly expressed in lung and brain.INDUCTION Down-regulated by LPS.SIMILARITY Belongs to the FGGY kinase family. UniProt Q9UHJ6 1 EQUAL 478 EQUAL GO 0050277 GO molecular function Reactome Database ID Release 77 8959703 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8959703 Reactome Database ID Release 77 8959719 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8959719 Reactome R-HSA-8959719 2 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8959719.2 22682222 Pubmed 2012 The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism Haschemi, Arvand Kosma, Paul Gille, Lars Evans, Charles R Burant, CF Starkl, Philipp Knapp, Bernhard Haas, Robert Schmid, Johannes A Jandl, Christoph Amir, Shahzada Lubec, Gert Park, Jaehong Esterbauer, Harald Bilban, Martin Brizuela,莱昂纳多 Pospisilik, J Andrew Otterbein, Leo E Wagner, Oswald Cell Metab. 15:813-26 18186520 Pubmed 2008 Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene Wamelink, Mirjam M C Struys, Eduard A Jansen, Erwin E W Levtchenko, Elena N Zijlstra, Fokje S M Engelke, Udo Blom, Henk J Jakobs, Cornelis Wevers, RA Hum. Mutat. 29:532-6 18775706 Pubmed 2008 Characterization of mammalian sedoheptulokinase and mechanism of formation of erythritol in sedoheptulokinase deficiency Kardon, Tamas Stroobant, Vincent Veiga-da-Cunha, M Schaftingen, Emile Van FEBS Lett. 582:3330-4 5-Phosphoribose 1-diphosphate biosynthesis 5-Phosphoribose 1-diphosphate biosynthesis PRPP biosynthesis Synthesis of cytosolic 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) from D-ribose 5-phosphate 5-Phospho-alpha-D-ribose 1-diphosphate (PRPP)key intermediate in both the de novo and salvage pathways of purine and pyrimidine synthesis. PRPP and the enzymatic activity responsible for its synthesis were first described by Kornberg et al. (1955). The enzyme, phosphoribosyl pyrophosphate synthetase 1, has been purified from human erythrocytes and characterized biochemically. The purified enzyme readily forms multimers; its smallest active form appears to be a dimer and for simplicity it is annotated as a dimer here. It specifically catalyzes the transfer of pyrophosphate from ATP or dATP to D-ribose 5-phosphate, and has an absolute requirement for Mg++ and orthophosphate (Fox and Kelley 1971; Roth et al. 1974). The significance of the reaction with dATP in vivo is unclear, as the concentration of cytosolic dATP is normally much lower than that of ATP. The importance of this enzyme for purine synthesis in vivo has been established by demonstrating excess phosphoribosyl pyrophosphate synthetase activity, correlated with elevated enzyme levels or altered enzyme properties, in individuals whose rates of uric acid production are constitutively abnormally high (Becker and Kim 1987; Roessler et al. 1993).

Molecular cloning studies have revealed the existence of two additional genes that encode phosphoribosyl pyrophosphate synthetase-like proteins, one widely expressed (phosphoribosyl pyrophosphate synthetase 2) and one whose expression appears to be confined to the testis (phosphoribosyl pyrophosphate synthetase 1-like 1) (Taira et al. 1989; 1991). Neither of these proteins has been purified and characterized enzymatically, nor have variations in the abundance or sequence of either protein been associated with alterations in human nucleotide metabolism (Roessler et al. 1993; Becker et al. 1996), so their dimerization and ability to catalyze the synthesis of PRPP from D-ribose 5-phosphate are inferred here on the basis of their predicted amino acid sequence similarity to phosphoribosyl pyrophosphate synthetase 1. Authored: D'Eustachio, P, 2004-02-09 03:00:00 Edited: D'Eustachio, P, 0000-00-00 00:00:00 2.7.6.1 D-ribose 5-phosphate + 2'-deoxyadenosine 5'-triphosphate (dATP) => 5-Phospho-alpha-D-ribose 1-diphosphate (PRPP) + 2'-deoxyadenosine 5'-monophosphate D-ribose 5-phosphate + 2'-deoxyadenosine 5'-triphosphate (dATP) => 5-Phospho-alpha-D-ribose 1-diphosphate (PRPP) + 2'-deoxyadenosine 5'-monophosphate Cytosolic phosphoribosyl pyrophosphate synthetase 1 catalyzes the reaction of D-ribose 5-phosphate and dATP to form 5-phospho-alpha-D-ribose 1-diphosphate and 2'-deoxyadenosine 5'-monophosphate. While phosphoribosyl pyrophosphate synthetase 1 works well with either ATP or dATP as a substrate in vitro, the extent of the dATP reaction in vivo is unclear, as cellular dATP concentrations are normally very low (Fox and Kelley 1971). Reactome DB_ID: 110644 1 dATP [ChEBI:16284] dATP 2'-deoxyadenosine 5'-triphosphate Deoxyadenosine triphosphate Deoxyadenosine 5'-triphosphate ChEBI 16284 Reactome DB_ID: 73578 1 Reactome DB_ID: 109386 1 2'-deoxyadenosine 5'-monophosphate [ChEBI:17713] 2'-deoxyadenosine 5'-monophosphate ChEBI 17713 Reactome DB_ID: 73566 1 5-O-phosphono-alpha-D-ribofuranosyl二磷酸[ChEBI:17111] 5-O-phosphono-alpha-D-ribofuranosyl二磷酸 ChEBI 17111 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 73485 PRPS1 dimer [cytosol] PRPS1 dimer phosphoribosyl pyrophosphate synthetase 1 holoenzyme Reactome DB_ID: 73483 2 UniProt:P60891 PRPS1 PRPS1 PRPS1 FUNCTION Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.ACTIVITY REGULATION Activated by magnesium and inorganic phosphate.PATHWAY Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate from D-ribose 5-phosphate (route I): step 1/1.SUBUNIT Homodimer. The active form is probably a hexamer composed of 3 homodimers.DISEASE Phosphoribosyl pyrophosphate synthetase I deficiency is a rare condition caused by mutations in PRPS1 that lead to variable disease phenotypes including optic atrophy, retinitis pigmentosa, ataxia, peripheral neuropathy and hearing loss.DISEASE A mutation in PRPS1 has been found in a patient with a phenotype that bridges that of PRSPS1 superactivity and ARTS syndrome with uric acid overproduction without gout but with recurrent infections, sensorineural hearing loss and motor neuropathy. The intermediate phenotype may be because Leu-142 variant affects both allosteric sites that are involved in inhibition of PRPS1 and the ATP-binding site, which suggests that this substitution can result both in a gain-of-function and loss-of-function of PRPP synthetase.SIMILARITY Belongs to the ribose-phosphate pyrophosphokinase family. UniProt P60891 2 EQUAL 318 EQUAL Reactome Database ID Release 77 73485 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=73485 Reactome R-HSA-73485 2 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-73485.2 GO 0004749 GO molecular function Reactome Database ID Release 77 73486 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=73486 Reactome Database ID Release 77 111215 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=111215 Reactome R-HSA-111215 4 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-111215.4 4328836 Pubmed 1971 Human phosphoribosylpyrophosphate synthetase Fox, IH Kelley, WN J Biol Chem 246:5739-5748 ACTIVATION Reactome Database ID Release 77 9034462 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9034462 Reactome R-HSA-9034462 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9034462.1 Reactome DB_ID: 29372 hydrogenphosphate [ChEBI:43474] hydrogenphosphate [PO3(OH)](2-) HYDROGENPHOSPHATE离子 hydrogen phosphate [P(OH)O3](2-) HPO4(2-) phosphate INORGANIC PHOSPHATE GROUP ChEBI 43474 ACTIVATION Reactome Database ID Release 77 9034457 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=9034457 Reactome R-HSA-9034457 1 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9034457.1 Reactome DB_ID: 29926 2.7.6.1 D-ribose 5-phosphate + ATP => 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) + adenosine 5'-monophosphate D-ribose 5-phosphate + ATP => 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) + adenosine 5'-monophosphate addition of diphosphate (PP) to ribose 5-phosphate to form 5'-Phospho-alpha-D-ribose 1-diphosphate (PRPP) Cytosolic phophoribosyl pyrophosphate synthetase catalyzes the reaction of D-ribose 5-phosphate and ATP to form 5-phospho-alpha-D-ribose and AMP. Three isoforms of the enzyme have been described. The first has been purified and characterized biochemically (Fox and Kelley 1971). The others are known only as inferred protein products of cloned genes; their catalytic properties have not been determined. Reactome DB_ID: 73578 1 Reactome DB_ID: 113592 1 Reactome DB_ID: 73566 1 Reactome DB_ID: 76577 1 adenosine 5'-monophosphate [ChEBI:16027] adenosine 5'-monophosphate ChEBI 16027 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 189812 PRPS2 dimer, PRPS1L dimer [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 77 111174 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=111174 Reactome Database ID Release 77 73580 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=73580 Reactome R-HSA-73580 3 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-73580.3 Reactome Database ID Release 77 73843 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=73843 Reactome R-HSA-73843 2 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-73843.2 14392173 Pubmed 1955 Enzymatic synthesis and properties of 5-phosphoribosylpyrophosphate Kornberg, A Lieberman, I Simms, ES J Biol Chem 215:389-402 4358634 Pubmed 1974 Purification and properties of phosphoribosyl pyrophosphate synthetase from rat liver Roth, DG Shelton, E Deuel, TF J Biol Chem 249:291-296 8702702 Pubmed 1996 Overexpression of the normal phosphoribosylpyrophosphate synthetase 1 isoform undelies catalytic superactivity of human phosphoribosylpyrophosphate synthetase Becker, MA Taylor, W Smith, PR Ahmed, M J Biol Chem 271:19894-19899 8253776 Pubmed 1993 Human X-linked phosphoribosylpyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene Roessler, BJ Nosal, JM Smith, PR Heidler, SA Palella, TD Switzer, RL Becker, MA J Biol Chem 268:26476-26481 2168892 Pubmed 1990 A human testis-specific mRNA for phosphoribosylpyrophosphate synthetase that initiates from a non-AUG codon Taira, M Iizasa, T Shimada, H Kudoh, J Shimizu, N Tatibana, M J Biol Chem 265:16491-16497 2537655 Pubmed 1989 Tissue-differential expression of two distinct genes for phosphoribosyl pyrophosphate synthetase and existence of the testic-specific transcript Taira, M Iizasa, T Yamada, K Shimada, H Tatibana, M Biochim Biophys Acta 1007:203-208 2444588 Pubmed 1987 Regulation of purine synthesis de novo in human fibroblasts by purine nucleotides and phosphoribosylpyrophosphate Becker, MA Kim, M J Biol Chem 262:14531-14537 GO 0006015 GO biological process Reactome Database ID Release 77 71336 Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71336 Reactome R-HSA-71336 6 Reactome稳定的标识符。使用这个URL connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71336.6 3790084 Pubmed 1987 pentose-cycle中间体在生活的内容r in starved, fed ad libitum and meal-fed rats. Casazza, JP Veech, RL Biochem J 236:635-41 18987987 Pubmed 2008 The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review Wamelink, Mirjam M C Struys, Eduard A Jakobs, Cornelis J Inherit Metab Dis 31:703-17 GO 0006098 GO biological process