Galactose catabolism (Homo sapiens)

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62, 5, 81, 743, 9cytosolUDP-GalPGM2L1 G6PADPGalMg2+ PGM1 GALTPGM:Mg2+GALE GALE:NAD+ dimerPGM2 G1PUDP-GlcATPGALK1ATPNAD+ Gal1P67


Description

The main sources of galactose in the human diet are milk and milk products. The disaccharide lactose from these sources is hydrolyzed in the intestine to its constituent monosaccharides, glucose and galactose. Galactose is metabolized primarily in the liver in a sequence of three reactions that yield one molecule of glucose 1-phosphate per molecule of galactose. First, it is phosphorylated to yield galactose 1-phosphate. Then, galactose 1-phosphate and UDP-glucose react to form UDP-galactose and glucose 1-phosphate, and UDP-galactose undergoes epimerization to form UDP-glucose. In a reaction shared with other pathways, glucose 1-phosphate can be converted into glucose 6-phosphate (Holton et al. 2001; Elsas and Lai 2001). View original pathway at:Reactome.

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Pathway is converted from Reactome ID: 70370
Reactome-version 
Reactome version: 64

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Bibliography

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  1. Ai Y, Basu M, Bergsma DJ, Stambolian D.; ''Comparison of the enzymatic activities of human galactokinase GALK1 and a related human galactokinase protein GK2.''; PubMed Europe PMC Scholia
  2. Reichardt JK, Packman S, Woo SL.; ''Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase.''; PubMed Europe PMC Scholia
  3. March RE, Putt W, Hollyoake M, Ives JH, Lovegrove JU, Hopkinson DA, Edwards YH, Whitehouse DB.; ''The classical human phosphoglucomutase (PGM1) isozyme polymorphism is generated by intragenic recombination.''; PubMed Europe PMC Scholia
  4. Maliekal P, Sokolova T, Vertommen D, Veiga-da-Cunha M, Van Schaftingen E.; ''Molecular identification of mammalian phosphopentomutase and glucose-1,6-bisphosphate synthase, two members of the alpha-D-phosphohexomutase family.''; PubMed Europe PMC Scholia
  5. Reichardt JK, Woo SL.; ''Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase.''; PubMed Europe PMC Scholia
  6. Schulz JM, Watson AL, Sanders R, Ross KL, Thoden JB, Holden HM, Fridovich-Keil JL.; ''Determinants of function and substrate specificity in human UDP-galactose 4'-epimerase.''; PubMed Europe PMC Scholia
  7. Veiga-da-Cunha M, Vleugels W, Maliekal P, Matthijs G, Van Schaftingen E.; ''Mammalian phosphomannomutase PMM1 is the brain IMP-sensitive glucose-1,6-bisphosphatase.''; PubMed Europe PMC Scholia
  8. Elsas LJ, Lai K.; ''The molecular biology of galactosemia.''; PubMed Europe PMC Scholia
  9. Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM.; ''Crystallographic evidence for Tyr 157 functioning as the active site base in human UDP-galactose 4-epimerase.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115079view17:02, 25 January 2021ReactomeTeamReactome version 75
113521view11:59, 2 November 2020ReactomeTeamReactome version 74
112720view16:12, 9 October 2020ReactomeTeamReactome version 73
101636view11:49, 1 November 2018ReactomeTeamreactome version 66
101172view21:36, 31 October 2018ReactomeTeamreactome version 65
100698view20:09, 31 October 2018ReactomeTeamreactome version 64
100248view16:54, 31 October 2018ReactomeTeamreactome version 63
99800view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99350view12:48, 31 October 2018ReactomeTeamreactome version 62
93647view11:29, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
G1PMetaboliteCHEBI:16077 (ChEBI)
G6PMetaboliteCHEBI:17665 (ChEBI)
GALE ProteinQ14376 (Uniprot-TrEMBL)
GALE:NAD+ dimerComplexR-HSA-70363 (Reactome)
GALK1ProteinP51570 (Uniprot-TrEMBL)
GALTProteinP07902 (Uniprot-TrEMBL)
Gal1PMetaboliteCHEBI:17973 (ChEBI)
GalMetaboliteCHEBI:17118 (ChEBI)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NAD+ MetaboliteCHEBI:15846 (ChEBI)
PGM1 ProteinP36871 (Uniprot-TrEMBL)
PGM2 ProteinQ96G03 (Uniprot-TrEMBL)
PGM2L1 ProteinQ6PCE3 (Uniprot-TrEMBL)
PGM:Mg2+ComplexR-HSA-453132 (Reactome)
UDP-GalMetaboliteCHEBI:18307 (ChEBI)
UDP-GlcMetaboliteCHEBI:18066 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-70355 (Reactome)
ATPR-HSA-70355 (Reactome)
G1PArrowR-HSA-70361 (Reactome)
G1PR-HSA-70427 (Reactome)
G6PArrowR-HSA-70427 (Reactome)
GALE:NAD+ dimermim-catalysisR-HSA-70369 (Reactome)
GALK1mim-catalysisR-HSA-70355 (Reactome)
GALTmim-catalysisR-HSA-70361 (Reactome)
Gal1PArrowR-HSA-70355 (Reactome)
Gal1PR-HSA-70361 (Reactome)
GalR-HSA-70355 (Reactome)
PGM:Mg2+mim-catalysisR-HSA-70427 (Reactome)
R-HSA-70355 (Reactome) Cytosolic galactokinase (GALK1) catalyses the reaction of ATP and D-galactose to form ADP and D-galactose 1-phosphate (Ai at al. 1995).
R-HSA-70361 (Reactome) Cytosolic galactose-1-phosphate uridylyltransferase (GALT) catalyzes the reaction of alpha-D-galactose 1-phosphate and UDP glucose to form D-glucose 1-phosphate and UDP galactose (Reichardt & Woo 1991).
R-HSA-70369 (Reactome) Cytosolic UDP-galactose 4-epimerase catalyzes the interconversion of UDP-D-galactose and UDP-D-glucose (Schulz et al. 2004). The active form of the enzyme is a homodimer with one molecule of bound NAD+ per monomer (Thoden et al. 2000).
R-HSA-70427 (Reactome) Cytosolic phosphoglucomutase (PGM) catalyzes the reversible conversion of glucose 1-phosphate to glucose 6-phosphate. Two PGM isoenzymes, both monomers, have been identified. PGM1 is the major form found in most tissues except erythrocytes, where PGM2 is abundant (March et al. 1993; Parrington et al. 1968; Putt et al. 1993). PGM2 also has substantial phosphopentomutase activity and its primary physiological in normal tissues in vivo is not clear. Cytosolic glucose 1,6-bisphosphate synthase (PGM2L1) also possesses phosphoglucomutase activity (Maliekal et al. 2007, Veiga-da-Cunha et al. 2008).
UDP-GalArrowR-HSA-70361 (Reactome)
UDP-GalR-HSA-70369 (Reactome)
UDP-GlcArrowR-HSA-70369 (Reactome)
UDP-GlcR-HSA-70361 (Reactome)
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