Formation of xylulose-5-phosphate (Homo sapiens)

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91267112, 3, 8, 10, 131, 4, 5, 14cytosolSORD tetramerKGPDCNADHH+CRYL1 dimerNADPHCRYL1 SORD XYLBNADP+NADP+Zn2+ DCXR tetramerAKR1A1H+NADHH+NAD+CO2D-xylulose3-dehydro-L-gulonateDCXR XY5PL-gulonateNADPHNAD+xylitolL-xyluloseD-glucuronateATPADPH+2, 1312104, 571


Description

The conversion of D-glucuronate to D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway, proceeds via L-gulonate, 3-dehydro-L-gulonate, L-xylulose, xylitol, and D-xylulose (Wamelink et al. 2008). D-glucuronate can be generated via the degradation of glucuronidated proteins. This pathway would have the effect of returning it to the pentose phosphate pathway or glycolysis. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 5661270
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: D'Eustachio, Peter

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Bibliography

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  1. Maret W, Auld DS.; ''Purification and characterization of human liver sorbitol dehydrogenase.''; PubMed Europe PMC Scholia
  2. Bunker RD, Bulloch EM, Dickson JM, Loomes KM, Baker EN.; ''Structure and function of human xylulokinase, an enzyme with important roles in carbohydrate metabolism.''; PubMed Europe PMC Scholia
  3. Alvarez A, Martínez A, Ibarra B, Medina C, Bracamontes M, Perea J, Vaca G.; ''Membrane-bound sorbitol dehydrogenase in human red blood cells. Studies in normal subjects and in enzyme-deficient subjects with congenital cataracts.''; PubMed Europe PMC Scholia
  4. Barski OA, Gabbay KH, Grimshaw CE, Bohren KM.; ''Mechanism of human aldehyde reductase: characterization of the active site pocket.''; PubMed Europe PMC Scholia
  5. Nakagawa J, Ishikura S, Asami J, Isaji T, Usami N, Hara A, Sakurai T, Tsuritani K, Oda K, Takahashi M, Yoshimoto M, Otsuka N, Kitamura K.; ''Molecular characterization of mammalian dicarbonyl/L-xylulose reductase and its localization in kidney.''; PubMed Europe PMC Scholia
  6. Wamelink MM, Struys EA, Jakobs C.; ''The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review.''; PubMed Europe PMC Scholia
  7. WINKELMAN J, ASHWELL G.; ''Enzymic formation of L-xylulose from beeta-keto-L-gulonic acid.''; PubMed Europe PMC Scholia
  8. Karlsson C, Maret W, Auld DS, Höög JO, Jörnvall H.; ''Variability within mammalian sorbitol dehydrogenases. The primary structure of the human liver enzyme.''; PubMed Europe PMC Scholia
  9. Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL.; ''X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.''; PubMed Europe PMC Scholia
  10. El-Kabbani O, Ishikura S, Darmanin C, Carbone V, Chung RP, Usami N, Hara A.; ''Crystal structure of human L-xylulose reductase holoenzyme: probing the role of Asn107 with site-directed mutagenesis.''; PubMed Europe PMC Scholia
  11. Ishikura S, Usami N, Araki M, Hara A.; ''Structural and functional characterization of rabbit and human L-gulonate 3-dehydrogenase.''; PubMed Europe PMC Scholia
  12. Boué F, Blais J, Sullivan R.; ''Surface localization of P34H an epididymal protein, during maturation, capacitation, and acrosome reaction of human spermatozoa.''; PubMed Europe PMC Scholia
  13. Wang YM, Van Eys J.; ''The enzymatic defect in essential pentosuria.''; PubMed Europe PMC Scholia
  14. Pierce SB, Spurrell CH, Mandell JB, Lee MK, Zeligson S, Bereman MS, Stray SM, Fokstuen S, MacCoss MJ, Levy-Lahad E, King MC, Motulsky AG.; ''Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114757view16:24, 25 January 2021ReactomeTeamReactome version 75
113201view11:26, 2 November 2020ReactomeTeamReactome version 74
112426view15:37, 9 October 2020ReactomeTeamReactome version 73
101330view11:21, 1 November 2018ReactomeTeamreactome version 66
100868view20:54, 31 October 2018ReactomeTeamreactome version 65
100409view19:28, 31 October 2018ReactomeTeamreactome version 64
99957view16:12, 31 October 2018ReactomeTeamreactome version 63
99513view14:45, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99155view12:41, 31 October 2018ReactomeTeamreactome version 62
93383view11:22, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
3-dehydro-L-gulonateMetaboliteCHEBI:57655 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
AKR1A1ProteinP14550 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
CO2MetaboliteCHEBI:16526 (ChEBI)
CRYL1 ProteinQ9Y2S2 (Uniprot-TrEMBL)
CRYL1 dimerComplexR-HSA-5661289 (Reactome)
D-glucuronateMetaboliteCHEBI:15748 (ChEBI)
D-xyluloseMetaboliteCHEBI:17140 (ChEBI)
DCXR ProteinQ7Z4W1 (Uniprot-TrEMBL)
DCXR tetramerComplexR-HSA-5660027 (Reactome)
H+MetaboliteCHEBI:15378 (ChEBI)
KGPDCR-HSA-5661266 (Reactome)
L-gulonateMetaboliteCHEBI:13115 (ChEBI)
L-xyluloseMetaboliteCHEBI:17399 (ChEBI)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
SORD ProteinQ00796 (Uniprot-TrEMBL)
SORD tetramerComplexR-HSA-5652211 (Reactome)
XY5PMetaboliteCHEBI:57737 (ChEBI)
XYLBProteinO75191 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
xylitolMetaboliteCHEBI:17151 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
3-dehydro-L-gulonateArrowR-HSA-5661290 (Reactome)
3-dehydro-L-gulonateR-HSA-5662473 (Reactome)
ADPArrowR-HSA-5662466 (Reactome)
AKR1A1mim-catalysisR-HSA-5661256 (Reactome)
ATPR-HSA-5662466 (Reactome)
CO2ArrowR-HSA-5662473 (Reactome)
CRYL1 dimermim-catalysisR-HSA-5661290 (Reactome)
D-glucuronateR-HSA-5661256 (Reactome)
D-xyluloseArrowR-HSA-5662471 (Reactome)
D-xyluloseR-HSA-5662466 (Reactome)
DCXR tetramermim-catalysisR-HSA-5661240 (Reactome)
H+ArrowR-HSA-5661290 (Reactome)
H+ArrowR-HSA-5662471 (Reactome)
H+R-HSA-5661240 (Reactome)
H+R-HSA-5661256 (Reactome)
KGPDCmim-catalysisR-HSA-5662473 (Reactome)
L-gulonateArrowR-HSA-5661256 (Reactome)
L-gulonateR-HSA-5661290 (Reactome)
L-xyluloseArrowR-HSA-5662473 (Reactome)
L-xyluloseR-HSA-5661240 (Reactome)
NAD+R-HSA-5661290 (Reactome)
NAD+R-HSA-5662471 (Reactome)
NADHArrowR-HSA-5661290 (Reactome)
NADHArrowR-HSA-5662471 (Reactome)
NADP+ArrowR-HSA-5661240 (Reactome)
NADP+ArrowR-HSA-5661256 (Reactome)
NADPHR-HSA-5661240 (Reactome)
NADPHR-HSA-5661256 (Reactome)
R-HSA-5661240 (Reactome) L-xylulose reductase (DCXR, also known as dicarbonyl/L-xylulose reductase) catalyzes the reversible NADPH dependent reduction of cytosolic L-xylulose to xylitol (Nakagawa et al. 2002). The enzyme is a tetramer (El Kabbani et al.2004) and may be associated with the plasma membrane (Boue et al. 1996). Mutations that inactivate DCXR are associated with essential pentosuria (Pierce et al. 2011; Wang & van Eys 1970).
R-HSA-5661256 (Reactome) Cytosolic AKR1A1 (Aldo-keto reductase family 1 member A1) catalyzes the reduction by NADPH of D-glucuronate to L-gulonate (Barski et al. 1995).
R-HSA-5661290 (Reactome) Cytosolic CRYL1 (lambda-crystallin homolog, also known as L-gulonate 3-dehydrogenase) dimer catalyzes the NAD-dependent dehydrogenation of L-gulonate to form 3-dehydro-L-gulonate. The CRYL1 protein also functions as a lens crystallin, hence its name (Ishikura et al. 2005).
R-HSA-5662466 (Reactome) Cytosolic xylulose kinase (XYLB) catalyzes the phosphorylation of D-xylulose to form D-xylulose-5-phosphate (XY5P) (Bunker et al. 2013).
R-HSA-5662471 (Reactome) Tetrameric sorbitol dehydrogenase (SORD tetramer) catalyzes the NAD-dependent oxidation of xylitol to form D-xylulose (Alvarez et al. 1993; Karlsson et al. 1989; Maret & Auld 1988; Pauly et al. 2003).
R-HSA-5662473 (Reactome) Cytosolic dehydro-L-gulonate decarboxylase (KGPDC) catalyzes the conversion of 3-dehydro-L-gulonate to L-xylulose and CO2. Studies in vivo provide indirect but strong evidence that this reaction occurs in humans and guinea pigs and dehydro-L-gulonate decarboxylase enzyme has been partially purified from guinea pigs (Winkelman & Ashwell 1961). Its amino acid sequence is unknown, however.
SORD tetramermim-catalysisR-HSA-5662471 (Reactome)
XY5PArrowR-HSA-5662466 (Reactome)
XYLBmim-catalysisR-HSA-5662466 (Reactome)
xylitolArrowR-HSA-5661240 (Reactome)
xylitolR-HSA-5662471 (Reactome)
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