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MetaCyc Pathway: Rapoport-Luebering glycolytic shunt
Inferred from experiment

Enzyme View:

Pathway diagram: Rapoport-Luebering glycolytic shunt

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: BiosynthesisMetabolic Regulators Biosynthesis

Some taxa known to possess this pathway include : Dictyostelium discoideum, Homo sapiens

Expected Taxonomic Range: Aves, Dictyosteliida, Mammalia

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].

Finally, 2,3-BPG is a key regulator of oxygen release from erythrocytes, by preferentially binding to deoxyhemoglobin [Benesch67, Benesch68].

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].

Created 17-Dec-2009 by Caspi R, SRI International


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

Benesch68: Benesch R, Benesch RE, Yu CI (1968). "Reciprocal binding of oxygen and diphosphoglycerate by human hemoglobin." Proc Natl Acad Sci U S A 59(2);526-32. PMID: 5238982

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

Downes82: Downes CP, Mussat MC, Michell RH (1982). "The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane." Biochem J 203(1);169-77. PMID: 6285891

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

FothergillGilmo93: Fothergill-Gilmore LA, Michels PA (1993). "Evolution of glycolysis." Prog Biophys Mol Biol 59(2);105-235. PMID: 8426905

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

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

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

Bresolin83: Bresolin N, Ro YI, Reyes M, Miranda AF, DiMauro S (1983). "Muscle phosphoglycerate mutase (PGAM) deficiency: a second case." Neurology 33(8);1049-53. PMID: 6308514

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

DiMauro81: DiMauro S, Miranda AF, Khan S, Gitlin K, Friedman R (1981). "Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy." Science 212(4500);1277-9. PMID: 6262916

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

FothergillGilmo89: Fothergill-Gilmore LA, Watson HC (1989). "The phosphoglycerate mutases." Adv Enzymol Relat Areas Mol Biol 62;227-313. PMID: 2543188

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

Hallows12: Hallows WC, Yu W, Denu JM (2012). "Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation." J Biol Chem 287(6);3850-8. PMID: 22157007

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

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

Pritlove06: Pritlove DC, Gu M, Boyd CA, Randeva HS, Vatish M (2006). "Novel placental expression of 2,3-bisphosphoglycerate mutase." Placenta 27(8);924-7. PMID: 16246416

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

Tsujino93: Tsujino S, Shanske S, Sakoda S, Fenichel G, DiMauro S (1993). "The molecular genetic basis of muscle phosphoglycerate mutase (PGAM) deficiency." Am J Hum Genet 52(3);472-7. PMID: 8447317

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sat Apr 30, 2016, biocyc14.