This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Metabolic Regulators Biosynthesis|
The Rapoport-Luebering glycolytic shunt, which has been documented in Dictyostelium, birds and mammals, generates and dephosphorylates 2,3-diphospho-D-glycerate (2,3-BPG) [Kauffman02, Rapoport77].
The enzyme that generates 2,3-BPG is the bifunctional bisphosphoglycerate mutase. The enzyme converts the glycolytic intermediate 1,3-bisphospho-D-glycerate (1,3-BPG) to 2,3-BPG, and also acts as a phosphatase, converting 2,3-BPG to 3-phospho-D-glycerate (3-PG), which then reenters the main glycolytic pathway.
During the standard glycolysis pathway 1,3-BPG is converted to 3-PG in a single step, generating an ATP molecule, and by directing 1,3-BPG to the Rapoport-Luebering shunt the cell gives up the production of this ATP molecule. However, the purpose of this shunt is the production of 2,3-BPG, which is a key regulator in the cell.
First, 2,3-BPG fulfills an essential role in glycolysis by priming the phosphoglycerate mutase reaction that converts 3-PG to 2-phospho-D-glycerate (2-PG) [FothergillGilmo93]. In addition, 2,3-BPG provides a molecular link between the turnover of phosphorylated inositol derivatives and glycolytic flux, being a regulator of key enzymes such as type I inositol-1,4,5-trisphosphate 5-phosphatase [Downes82] and phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 [Drayer96].
Recently a new enzyme activity in this pathway has been discovered [Cho08]. 2,3-bisphosphoglycerate 3-phosphatase catalyzes the direct production of 2-PG from 2,3-BPG, bypassing phosphoglycerate mutase. The enzyme that catalyzes this activity, which is encoded by the MINPP1 gene, has been previously known as multiple inositol polyphosphate phosphatase 1, and thus 2,3-bisphosphoglycerate 3-phosphatase is a new activity attributed to it. The enzyme from Dictyostelium discoideum has been characterized, and total activity in erythrocytes was equivalent to the level of the phosphatase activity of 2,3-BPG synthase/2-phosphatase [Cho08].
Benesch67: Benesch R, Benesch RE (1967). "The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin." Biochem Biophys Res Commun 26(2);162-7. PMID: 6030262
Cho08: Cho J, King JS, Qian X, Harwood AJ, Shears SB (2008). "Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt." Proc Natl Acad Sci U S A 105(16);5998-6003. PMID: 18413611
Drayer96: Drayer AL, Pesesse X, De Smedt F, Woscholski R, Parker P, Erneux C (1996). "Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase." Biochem Biophys Res Commun 225(1);243-9. PMID: 8769125
Kauffman02: Kauffman KJ, Pajerowski JD, Jamshidi N, Palsson BO, Edwards JS (2002). "Description and analysis of metabolic connectivity and dynamics in the human red blood cell." Biophys J 83(2);646-62. PMID: 12124254
Rapoport77: Rapoport I, Berger H, Elsner R, Rapoport S (1977). "PH-dependent changes of 2,3-bisphosphoglycerate in human red cells during transitional and steady states in vitro." Eur J Biochem 73(2);421-7. PMID: 14829
Barichard87: Barichard F, Joulin V, Henry I, Garel MC, Valentin C, Rosa R, Cohen-Solal M, Junien C (1987). "Chromosomal assignment of the human 2,3-bisphosphoglycerate mutase gene (BPGM) to region 7q34----7q22." Hum Genet 77(3);283-5. PMID: 2824335
Caffrey99: Caffrey JJ, Hidaka K, Matsuda M, Hirata M, Shears SB (1999). "The human and rat forms of multiple inositol polyphosphate phosphatase: functional homology with a histidine acid phosphatase up-regulated during endochondral ossification." FEBS Lett 442(1);99-104. PMID: 9923613
Chi99: Chi H, Tiller GE, Dasouki MJ, Romano PR, Wang J, O'keefe RJ, Puzas JE, Rosier RN, Reynolds PR (1999). "Multiple inositol polyphosphate phosphatase: evolution as a distinct group within the histidine phosphatase family and chromosomal localization of the human and mouse genes to chromosomes 10q23 and 19." Genomics 56(3);324-36. PMID: 10087200
Craxton97: Craxton A, Caffrey JJ, Burkhart W, Safrany ST, Shears SB (1997). "Molecular cloning and expression of a rat hepatic multiple inositol polyphosphate phosphatase." Biochem J 328 ( Pt 1);75-81. PMID: 9359836
Evans05: Evans MJ, Saghatelian A, Sorensen EJ, Cravatt BF (2005). "Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling." Nat Biotechnol 23(10);1303-7. PMID: 16200062
Gimm01: Gimm O, Chi H, Dahia PL, Perren A, Hinze R, Komminoth P, Dralle H, Reynolds PR, Eng C (2001). "Somatic mutation and germline variants of MINPP1, a phosphatase gene located in proximity to PTEN on 10q23.3, in follicular thyroid carcinomas." J Clin Endocrinol Metab 86(4);1801-5. PMID: 11297621
Joulin86: Joulin V, Peduzzi J, Romeo PH, Rosa R, Valentin C, Dubart A, Lapeyre B, Blouquit Y, Garel MC, Goossens M (1986). "Molecular cloning and sequencing of the human erythrocyte 2,3-bisphosphoglycerate mutase cDNA: revised amino acid sequence." EMBO J 5(9);2275-83. PMID: 3023066
Joulin88: Joulin V, Garel MC, Le Boulch P, Valentin C, Rosa R, Rosa J, Cohen-Solal M (1988). "Isolation and characterization of the human 2,3-bisphosphoglycerate mutase gene." J Biol Chem 263(30);15785-90. PMID: 2844822
Patterson10: Patterson A, Price NC, Nairn J (2010). "Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding." Acta Crystallogr Sect F Struct Biol Cryst Commun 66(Pt 11);1415-20. PMID: 21045285
Reynolds96: Reynolds SD, Johnston C, Leboy PS, O'Keefe RJ, Puzas JE, Rosier RN, Reynolds PR (1996). "Identification and characterization of a unique chondrocyte gene involved in transition to hypertrophy." Exp Cell Res 226(1);197-207. PMID: 8660956
Romano98: Romano PR, Wang J, O'Keefe RJ, Puzas JE, Rosier RN, Reynolds PR (1998). "HiPER1, a phosphatase of the endoplasmic reticulum with a role in chondrocyte maturation." J Cell Sci 111 ( Pt 6);803-13. PMID: 9472008
Sakoda88: Sakoda S, Shanske S, DiMauro S, Schon EA (1988). "Isolation of a cDNA encoding the B isozyme of human phosphoglycerate mutase (PGAM) and characterization of the PGAM gene family." J Biol Chem 263(32);16899-905. PMID: 2846553
Stafforini93: Stafforini DM, Rollins EN, Prescott SM, McIntyre TM (1993). "The platelet-activating factor acetylhydrolase from human erythrocytes. Purification and properties." J Biol Chem 268(6);3857-65. PMID: 8440681
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