Serine biosynthesis (Homo sapiens)

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271, 93, 8103, 854, 6cytosolATPSERINC4 PSPH:Mg2+ dimerPXLP-K200-PSAT1 SERINC1 NH3PXLP-K200-PSAT1dimerH2OATP3POPAPSPH PYRMg2+2OGSERINC2 PXLP-K56-SRR PiH+PXLP-K56-SRR dimerO-P-SerD-SerH2OMg2+ L-SerPHGDH SERINC3,5,(1,2,4)NAD+NADHSERINC5 SERINC3 L-Glu3PGPHGHD tetramerL-Ser


Description

L-Serine is needed in human brain in large amounts as precursor to important biomolecules such as nucleotides, phospholipids and the neurotransmitters glycine and D-serine. The pathway for its synthesis starts with 3-phosphoglycerate and it later needs glutamate as an amination agent. Deficiencies in the participating enzymes lead to severe neurological symptoms that are treatable with serine if treatment starts early (de Koning & Klomp 2004). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 977347
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Stephan, Ralf

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Bibliography

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  1. Xia M, Liu Y, Figueroa DJ, Chiu CS, Wei N, Lawlor AM, Lu P, Sur C, Koblan KS, Connolly TM.; ''Characterization and localization of a human serine racemase.''; PubMed Europe PMC Scholia
  2. de Koning TJ, Klomp LW.; ''Serine-deficiency syndromes.''; PubMed Europe PMC Scholia
  3. Foltyn VN, Bendikov I, De Miranda J, Panizzutti R, Dumin E, Shleper M, Li P, Toney MD, Kartvelishvily E, Wolosker H.; ''Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity.''; PubMed Europe PMC Scholia
  4. Usami Y, Wu Y, Göttlinger HG.; ''SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef.''; PubMed Europe PMC Scholia
  5. Tabatabaie L, de Koning TJ, Geboers AJ, van den Berg IE, Berger R, Klomp LW.; ''Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.''; PubMed Europe PMC Scholia
  6. Fackler OT.; ''Spotlight on HIV-1 Nef: SERINC3 and SERINC5 Identified as Restriction Factors Antagonized by the Pathogenesis Factor.''; PubMed Europe PMC Scholia
  7. Collet JF, Gerin I, Rider MH, Veiga-da-Cunha M, Van Schaftingen E.; ''Human L-3-phosphoserine phosphatase: sequence, expression and evidence for a phosphoenzyme intermediate.''; PubMed Europe PMC Scholia
  8. De Miranda J, Panizzutti R, Foltyn VN, Wolosker H.; ''Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine.''; PubMed Europe PMC Scholia
  9. De Miranda J, Santoro A, Engelender S, Wolosker H.; ''Human serine racemase: moleular cloning, genomic organization and functional analysis.''; PubMed Europe PMC Scholia
  10. Baek JY, Jun DY, Taub D, Kim YH.; ''Characterization of human phosphoserine aminotransferase involved in the phosphorylated pathway of L-serine biosynthesis.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114868view16:37, 25 January 2021ReactomeTeamReactome version 75
113314view11:38, 2 November 2020ReactomeTeamReactome version 74
112525view15:48, 9 October 2020ReactomeTeamReactome version 73
101700view14:38, 1 November 2018DeSlOntology Term : 'serine metabolic pathway' added !
101437view11:31, 1 November 2018ReactomeTeamreactome version 66
100976view21:09, 31 October 2018ReactomeTeamreactome version 65
100723view20:11, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2OGMetaboliteCHEBI:16810 (ChEBI)
3PGMetaboliteCHEBI:58272 (ChEBI)
3POPAMetaboliteCHEBI:30933 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
D-SerMetaboliteCHEBI:16523 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
L-GluMetaboliteCHEBI:29985 (ChEBI)
L-SerMetaboliteCHEBI:33384 (ChEBI)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
Mg2+MetaboliteCHEBI:18420 (ChEBI)
NAD+MetaboliteCHEBI:57540 (ChEBI)
NADHMetaboliteCHEBI:57945 (ChEBI)
NH3MetaboliteCHEBI:16134 (ChEBI)
O-P-SerMetaboliteCHEBI:15811 (ChEBI)
PHGDH ProteinO43175 (Uniprot-TrEMBL)
PHGHD tetramerComplexR-HSA-977346 (Reactome)
PSPH ProteinP78330 (Uniprot-TrEMBL)
PSPH:Mg2+ dimerComplexR-HSA-977344 (Reactome)
PXLP-K200-PSAT1 dimerComplexR-HSA-977345 (Reactome)
PXLP-K200-PSAT1 ProteinQ9Y617 (Uniprot-TrEMBL)
PXLP-K56-SRR ProteinQ9GZT4 (Uniprot-TrEMBL)
PXLP-K56-SRR dimerComplexR-HSA-9017153 (Reactome)
PYRMetaboliteCHEBI:15361 (ChEBI)
PiMetaboliteCHEBI:43474 (ChEBI)
SERINC1 ProteinQ9NRX5 (Uniprot-TrEMBL)
SERINC2 ProteinQ96SA4 (Uniprot-TrEMBL)
SERINC3 ProteinQ13530 (Uniprot-TrEMBL)
SERINC3,5,(1,2,4)ComplexR-HSA-8932973 (Reactome)
SERINC4 ProteinA6NH21 (Uniprot-TrEMBL)
SERINC5 ProteinQ86VE9 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2OGArrowR-HSA-977333 (Reactome)
3PGR-HSA-977348 (Reactome)
3POPAArrowR-HSA-977348 (Reactome)
3POPAR-HSA-977333 (Reactome)
ATPArrowR-HSA-9014741 (Reactome)
ATPArrowR-HSA-9014766 (Reactome)
D-SerArrowR-HSA-9014766 (Reactome)
D-SerR-HSA-9014741 (Reactome)
H+ArrowR-HSA-977348 (Reactome)
H2OArrowR-HSA-9014741 (Reactome)
H2OArrowR-HSA-9034539 (Reactome)
H2OR-HSA-977324 (Reactome)
L-GluR-HSA-977333 (Reactome)
L-SerArrowR-HSA-8932980 (Reactome)
L-SerArrowR-HSA-977324 (Reactome)
L-SerR-HSA-8932980 (Reactome)
L-SerR-HSA-9014766 (Reactome)
L-SerR-HSA-9034539 (Reactome)
Mg2+ArrowR-HSA-9014741 (Reactome)
Mg2+ArrowR-HSA-9014766 (Reactome)
NAD+R-HSA-977348 (Reactome)
NADHArrowR-HSA-977348 (Reactome)
NH3ArrowR-HSA-9014741 (Reactome)
NH3ArrowR-HSA-9034539 (Reactome)
O-P-SerArrowR-HSA-977333 (Reactome)
O-P-SerR-HSA-977324 (Reactome)
PHGHD tetramermim-catalysisR-HSA-977348 (Reactome)
PSPH:Mg2+ dimermim-catalysisR-HSA-977324 (Reactome)
PXLP-K200-PSAT1 dimermim-catalysisR-HSA-977333 (Reactome)
PXLP-K56-SRR dimermim-catalysisR-HSA-9014741 (Reactome)
PXLP-K56-SRR dimermim-catalysisR-HSA-9014766 (Reactome)
PXLP-K56-SRR dimermim-catalysisR-HSA-9034539 (Reactome)
PYRArrowR-HSA-9014741 (Reactome)
PYRArrowR-HSA-9034539 (Reactome)
PiArrowR-HSA-977324 (Reactome)
R-HSA-8932980 (Reactome) Serine incorporators 1-5 (SERINC1-5) are membrane-associated proteins that incorporate the polar amino acid serine (L-Ser) into membranes and facilitate the synthesis of the serine-derived lipids phosphatidylserine and sphingolipids. SERINC3 and 5 have recently been identified to be restrictors to HIV replication in human cells (Fackler 2015, Usami et al. 2015).
R-HSA-9014741 (Reactome) N-methyl D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission, learning, memory and synaptic plasticity. Their activity is modulated by the agonist glutamate and by the co-agonists D-Serine (D-Ser) and glycine (gly). In human brain, dimeric serine racemase (SRR), a pyridoxal 5'-phosphate-dependent enzyme (Smith et al. 2010), is a bifunctional enzyme mediating deamination and isomerisation of L-Serine. It can also catabolise D-Serine by alpha,beta-elimination of water to form pyruvate but at a rate 10-fold lower than for L-Serine (De Miranda et al. 2000, 2002, Foltyn et al. 2005). Thus, D-Ser homeostasis in neurons is modulated by SRR, and therefore indirectly, modulates NMDA receptors. Targeting SRR could find potential in neurodegenerative diseases (Canu et al. 2014). Mg2+ and ATP stimulate SRR (De Miranda et al. 2002).
R-HSA-9014766 (Reactome) N-methyl D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission, learning, memory and synaptic plasticity. Their activity is modulated by the agonist glutamate and by the co-agonists D-Serine (D-Ser) and glycine (gly). In human brain, dimeric serine racemase (SRR), a pyridoxal 5'-phosphate-dependent enzyme (Smith et al. 2010), is a bifunctional enzyme mediating mainly the catabolism of L-Serine by alpha,beta-elimination of water to form pyruvate (Foltyn et al. 2005). A small part of L-Serine does not undergo deamination so SRR can also mediate the minor reversible isomerisation of L-Ser to D-Ser (De Miranda et al. 2000, Xia et al. 2004). Thus, D-Ser homeostasis in neurons is modulated by SRR, and therefore indirectly, modulates NMDA receptors. Targeting SRR could find potential in neurodegenerative diseases (Canu et al. 2014). Mg2+ and ATP stimulate SRR (De Miranda et al. 2002).
R-HSA-9034539 (Reactome) N-methyl D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission, learning, memory and synaptic plasticity. Their activity is modulated by the agonist glutamate and by the co-agonists D-Serine (D-Ser) and glycine (gly). In human brain, dimeric serine racemase (SRR), a pyridoxal 5'-phosphate-dependent enzyme (Smith et al. 2010), is a bifunctional enzyme mediating mainly L-Serine catabolism by alpha,beta-elimination of water to form pyruvate (De Miranda et al. 2002, Foltyn et al. 2005). Part of L-Serine is not deaminated then SRR can also catalyse the isomerisation of L-Ser to D-Ser although this is very much a minor reaction. Thus, D-Ser homeostasis in neurons is modulated by SRR, and therefore indirectly, modulates NMDA receptors. Targeting SRR could find potential in neurodegenerative diseases (Canu et al. 2014). Mg2+ and ATP stimulate SRR (De Miranda et al. 2002).
R-HSA-977324 (Reactome) Dephosphorylation of O-phospho-L-serine to L-serine proceeds through a phospho-enzyme intermediate of the catalysing phosphatase PSP (Collet et al. 1997).
R-HSA-977333 (Reactome) The amino group needed for serine biosynthesis comes from glutamate (L-Glu). Its transfer onto 3-phosphonooxpyruvate (3POPA) is catalysed by PSAT1 dimer which needs pyridoxal phosphate (PXLP) as cofactor. (Baek et al. 2003)
R-HSA-977348 (Reactome) Serine biosynthesis starts from 3-phosphoglycerate, a glycolysis intermediate. Its dehydrogenation is catalysed by tetrameric phosphoglycerate dehydrogenase (PHGDH). (Tabatabaie et al. 2009).
SERINC3,5,(1,2,4)mim-catalysisR-HSA-8932980 (Reactome)
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