Lactose synthesis (Homo sapiens)

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42-42-41Golgi lumencytosolGlcGlcLacUDP-GalMn2+LALBA SLC2A1 SLC2A1 tetramerB4GALT1B4GALT1 LALBAB4GALT1:LALBAUDP552, 31


Description

Synthesis of the disaccharide lactose takes place within the Golgi apparatus of epithelial cells of the lactating mammary gland. The synthesis itself is a single chemical reaction of free glucose and UDP-galactose to form lactose and UDP. For this reaction to occur, glucose is transported from the cytosol into the Golgi lumen, and B4GALT1 interacts with LALBA (alpha-lactalbumin) to modulate its substrate specificity (Brew and Hill 1975). View original pathway at:Reactome.

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Reactome version: 61

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Bibliography

  1. Findlay JB, Brew K.; ''The complete amino-acid sequence of human -lactalbumin.''; PubMed Europe PMC Scholia
  2. Brew K, Hill RL.; ''Lactose biosynthesis.''; PubMed Europe PMC Scholia
  3. Andrews P.; ''Purification of lactose synthetase a protein from human milk and demonstration of its interaction with alpha-lactalbumin.''; PubMed Europe PMC Scholia
  4. Nemeth BA, Tsang SW, Geske RS, Haney PM.; ''Golgi targeting of the GLUT1 glucose transporter in lactating mouse mammary gland.''; PubMed Europe PMC Scholia
  5. Ramakrishnan B, Qasba PK.; ''Crystal structure of lactose synthase reveals a large conformational change in its catalytic component, the beta1,4-galactosyltransferase-I.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114750view16:23, 25 January 2021ReactomeTeamReactome version 75
113194view11:26, 2 November 2020ReactomeTeamReactome version 74
112420view15:36, 9 October 2020ReactomeTeamReactome version 73
101324view11:21, 1 November 2018ReactomeTeamreactome version 66
100861view20:53, 31 October 2018ReactomeTeamreactome version 65
100402view19:27, 31 October 2018ReactomeTeamreactome version 64
99950view16:12, 31 October 2018ReactomeTeamreactome version 63
99506view14:44, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99151view12:41, 31 October 2018ReactomeTeamreactome version 62
93609view11:28, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
B4GALT1 ProteinP15291 (Uniprot-TrEMBL)
B4GALT1:LALBAComplexR-HSA-5653885 (Reactome)
B4GALT1ProteinP15291 (Uniprot-TrEMBL)
GlcMetaboliteCHEBI:17925 (ChEBI)
LALBA ProteinP00709 (Uniprot-TrEMBL)
LALBAProteinP00709 (Uniprot-TrEMBL)
LacMetaboliteCHEBI:36219 (ChEBI)
Mn2+MetaboliteCHEBI:29035 (ChEBI)
SLC2A1 ProteinP11166 (Uniprot-TrEMBL)
SLC2A1 tetramerComplexR-HSA-5653881 (Reactome)
UDP-GalMetaboliteCHEBI:18307 (ChEBI)
UDPMetaboliteCHEBI:17659 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
B4GALT1:LALBAArrowR-HSA-5653886 (Reactome)
B4GALT1:LALBAmim-catalysisR-HSA-5653878 (Reactome)
B4GALT1R-HSA-5653886 (Reactome)
GlcArrowR-HSA-5653873 (Reactome)
GlcR-HSA-5653873 (Reactome)
GlcR-HSA-5653878 (Reactome)
LALBAR-HSA-5653886 (Reactome)
LacArrowR-HSA-5653878 (Reactome)
Mn2+ArrowR-HSA-5653886 (Reactome)
R-HSA-5653873 (Reactome) SLC2A1 (aka GLUT1) tetramer in the Golgi membrane mediates the facilitated diffusion of glucose from the cytosol into the Golgi lumen. SLC2A1, normally confined to the plasma membrane, is also abundant in the Golgi membranes of epithelial cells of the lactating mammary gland, as demonstrated experimentally in mice (Nemeth et al. 2000). It is not known how this physiological state-specific relocalization is regulated.
R-HSA-5653878 (Reactome) In the Golgi membrane, the B4GALT1 subunit of the B4GALT1:LALBA (beta-1,4-galactosyltransferase 1 : alpha-lactalbumin) complex catalyzes the transfer of galactose from UDP-galactose to free glucose to form galactose and UDP (Andrews 1970; Ramakrishnan & Qasba 2001). The representation here of a stable protein complex catalyzing the transformation of small molecule substrates provides a simplified view of the true reaction mechanism (Brew and Hill 1975), but is sufficient to identify the key participating molecules and their roles.
R-HSA-5653886 (Reactome) B4GALT1 (beta-1,4-galactosyltransferase 1) in the Golgi membrane associates with LALBA (alpha-lactalbumin) to form a heterodimer. This binding reaction is positively regulated by Mn2+ ions and UDP-galactose. This heterodimer has been observed both in solution in vitro and in crystalline form (Andrews 1970; Ramakrishnan & Qasba 2001). The galactosyltransferase enzyme is found in the Golgi membrane of many cell types. LALBA is expressed specifically in the lactating mammary gland. Binding LALBA modulates the specificity of the galactosyltransferase enzyme. Alone, B4GALT1 transfers galactose moieties to glycolipids and N-linked oligosaccharides of glycoproteins. Complexed with LALBA, it transfers galactose to free glucose to form lactose (Brew and Hill 1975).
SLC2A1 tetramermim-catalysisR-HSA-5653873 (Reactome)
UDP-GalArrowR-HSA-5653886 (Reactome)
UDP-GalR-HSA-5653878 (Reactome)
UDPArrowR-HSA-5653878 (Reactome)
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