Disorders of folate metabolism and transport (Homo sapiens)

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1, 2FTHFISHMT1QDPRMTHFD121111IntestinesMTHFR deficiencyMTHFD1 deficiencyMTHFS deficiencyFolate ReceptorAlpha DeficiencyDHFR deficiencyHeriditary Folate MalabsorptionGARTFSAMserineTHF5-Methyl-THFFTCDMTHFSNH4+MTHFCHL-glutamic acidSAHCO2glycineN-formimidoyl-L-glutamateHomocysteineDHFPyrimidine metabolismDNA methylationMethionineFolic acidPurine MetabolismProtein methylation5,10-Methylene-THFSLC46A1FOLR1Vitamin B125-formimino-THF5,10-Methenyl-THFGARFormyl-GARAICARFAICAR10-Formyl-THF5-Formyl-THFdTMPdUMPAICARTTSALDH1L1MSSHMTFITHFCHDHFRMTHFRMTHFD1Folic acidLiverBrainTHF5-Methyl-THF11SHMT111qDHF1spontaneousp-amino-benzoyl-polyglutamate17.8-dihydropterin11iminium ion1formaldehyde11spontaneousDiseaseCatalysisPathwayStimulationProteinMetaboliteConversionConnection to diseaseLegendProtein1cofactorComplexReduced folate carrier deficiencySLC19A1FIGLUALDH1L2FTHFDHNEDCASBQDPRD


Description

Folates play an essential role in one-carbon methyl transfer reactions, mediating several biological processes (e.g. DNA synthesis, epigentics by methylation, embryonic central nervous system development, cata-/anabolism of amino acids, and anabolism of thymidines, purines, and neurotransmitters. The biologically active folic acid derivative is 5,6,7,8-tetrahydrofolate (THF). Dietary folate is absorbed in the intestine, and stored in the liver for few months. [rephrased from chapter 10 of Blau et al, ISBN 3642403360 (978-3642403361)]. For more detail on MTHFR deficiency, please visit [1].

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Ontology Terms

 

Bibliography

  1. Fernando Scaglia, Nenad Blau; ''Disorders of Folate Metabolism and Transport''; Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic diseases, chapter 10, 2014
  2. Yuxiang Zheng, Lewis C Cantley; ''Toward a better understanding of folate metabolism in health and disease''; J Exp Med ., 2019 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128548view22:43, 11 February 2024EweitzSoften disease color, standardize case
126062view14:05, 31 March 2023DeSl
124234view09:57, 3 October 2022DeSlOntology Term : 'megaloblastic anemia' added !
124233view09:52, 3 October 2022DeSlUpdated OMIM-ID for MTHFD1 deficiency
124232view09:50, 3 October 2022DeSlOntology Term : 'glutamate formiminotransferase deficiency' added !
124231view09:50, 3 October 2022DeSlOntology Term : 'BH4-deficient hyperphenylalaninemia C' added !
124229view09:47, 3 October 2022DeSlConnected FIGLU-Uria to another interaction
124227view09:33, 3 October 2022DeSlAdded two more disorders not mentioned in the book
124226view09:29, 3 October 2022DeSlAdded comment for FTHFDH
124225view09:27, 3 October 2022DeSlAdded mitochondria drawing for ALDH1L2
124224view09:26, 3 October 2022DeSlAdded last missing disease from chapter, added more rhea IDs and proteins
124223view09:15, 3 October 2022DeSluPDATED SEVERAL PROTEINS AND DISEASES, STARTED ADDING RHEA idS TO INTERACTIONS
124221view08:56, 3 October 2022DeSlAdded legend
124220view08:55, 3 October 2022DeSlConverted GeneProduct MTHFD1 to Protein DataNode
124219view08:53, 3 October 2022DeSlAdded additional conversions from qDHF
124208view09:39, 29 September 2022DeSlAdded new metabolite reaction (qDHF) based on InchiKey
124207view08:35, 29 September 2022DeSlConverted FTHFI to textLabel, since there is no evidence found that this protein is active in humans.
124206view08:33, 29 September 2022DeSlAdded some more enzymes to THF->5,10-M-THF conversion based on lit. ref.
124205view08:18, 29 September 2022DeSlAdded new ref for whole PWM
124204view08:15, 29 September 2022DeSlUpdated interactions from textlabels, added mim-translocation, added rhea ID for SHMT-catalyzed reaction
124203view08:04, 29 September 2022DeSlAdded some more dteails on FTHFI
119256view19:45, 22 June 2021FinterlyAdded ISBN for book citation
117700view12:21, 22 May 2021EweitzModified title
108786view15:33, 29 January 2020DeSlReplaced A0A024RB99 (unreviewed) with P34897 (reviewed) for SHMT Protein
108078view11:47, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
104641view07:16, 7 June 2019JosienlandmanConverted interaction lines to diseases into graphical lines
104021view17:37, 25 April 2019IreneHemelModified description
102719view14:00, 21 January 2019DeSlModified description
102717view13:34, 21 January 2019DeSlModified description
98280view15:56, 15 August 2018DeSlModified description
98279view15:56, 15 August 2018DeSlChanged layout of disease nodes, and layout of right side of PW for readability.
97896view08:35, 21 June 2018Jessev1993Made lay-out changes
97595view09:21, 28 May 2018DeSlModified description
97594view09:11, 28 May 2018DeSlConnected last unconnected line.
97593view09:10, 28 May 2018DeSlAdded last disease, changed layout, created better connections for RDF.
97575view13:31, 25 May 2018DeSlMore layout changes, connected side metabolites where they should have been
97574view12:53, 25 May 2018DeSlChanged layout, added disease IDs.
97295view20:47, 7 May 2018Khanspersconnected interaction
97162view13:22, 2 May 2018Jessev1993Added Pathway annotations
97161view12:18, 2 May 2018Jessev1993updated annotations, replaced unknown nodes with textlabels
97160view08:53, 2 May 2018DeSlOntology Term : 'vitamin B12 deficiency' added !
97159view08:52, 2 May 2018DeSlOntology Term : 'vitamin metabolic disorder' added !
97158view08:51, 2 May 2018DeSlOntology Term : 'central nervous system neuron' added !
97157view08:51, 2 May 2018DeSlOntology Term : 'methylenetetrahydrofolate reductase deficiency pathway' added !
97156view08:50, 2 May 2018DeSlOntology Term : 'cerebral folate receptor alpha deficiency' added !
96956view22:46, 22 April 2018AndraOntology Term : 'folate metabolic pathway' added !
96924view06:09, 20 April 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
96914view13:05, 19 April 2018Jessev1993added data nodes
96891view12:48, 18 April 2018Jessev1993New pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
10-Formyl-THFMetaboliteCHEBI:15637 (ChEBI)
5,10-Methenyl-THFMetaboliteCHEBI:15638 (ChEBI)
5,10-Methylene-THFMetaboliteCHEBI:1989 (ChEBI)
5-Formyl-THFMetaboliteCHEBI:15640 (ChEBI)
5-Methyl-THFMetaboliteCHEBI:15641 (ChEBI)
5-formimino-THFMetaboliteCHEBI:15639 (ChEBI)
7.8-dihydropterinMetaboliteCHEBI:64277 (ChEBI) Reference [PMID:30587505] does not provide info on stereochemistry
AICARMetaboliteCHEBI:2030 (ChEBI)
AICARTProteinP31939 (Uniprot-TrEMBL)
ALDH1L1ProteinO75891 (Uniprot-TrEMBL) AKA FTHFD, cytosolic
ALDH1L2ProteinQ3SY69 (Uniprot-TrEMBL) AKA FTHFD, mitochondrial
CO2MetaboliteCHEBI:16526 (ChEBI)
DHFMetaboliteCHEBI:15633 (ChEBI) AKA 7,8-DHF
DHFRProteinB0YJ76 (Uniprot-TrEMBL)
DNA methylationPathwayWP3359 (WikiPathways)
FAICARMetaboliteCHEBI:18381 (ChEBI)
FITHFCHProteinO95954 (Uniprot-TrEMBL)
FOLR1ProteinP15328 (Uniprot-TrEMBL) AKA Folate receptor alpha
FTCDProteinO95954 (Uniprot-TrEMBL)
Folic acidMetaboliteCHEBI:27470 (ChEBI)
Formyl-GARMetaboliteCHEBI:18272 (ChEBI)
GARMetaboliteCHEBI:18349 (ChEBI)
GARTFProteinC9JKQ7 (Uniprot-TrEMBL)
HomocysteineMetaboliteCHEBI:17230 (ChEBI)
L-glutamic acidMetaboliteCHEBI:16015 (ChEBI)
MSProteinQ99707 (Uniprot-TrEMBL)
MTHFCHProtein3.5.4.9 (Enzyme Nomenclature) MTHFCH: methenyl-THF cyclohydrolase
MTHFD1ProteinP11586 (Uniprot-TrEMBL)
MTHFRProteinP42898 (Uniprot-TrEMBL)
MTHFSProteinENSG00000136371 (Ensembl)
MethionineMetaboliteCHEBI:16643 (ChEBI)
N-formimidoyl-L-glutamateMetaboliteCHEBI:58928 (ChEBI) Based on Rhea, the side metabolite is not Histidine
NH4+MetaboliteCHEBI:28938 (ChEBI)
Protein methylationPathwayWP4073 (WikiPathways)
Purine MetabolismPathwayWP4224 (WikiPathways)
Pyrimidine metabolismPathwayWP4225 (WikiPathways)
QDPRProteinP09417 (Uniprot-TrEMBL)
SAHMetaboliteCHEBI:16680 (ChEBI)
SAMMetaboliteCHEBI:67040 (ChEBI)
SHMT1ProteinP34896 (Uniprot-TrEMBL)
SHMTProteinP34897 (Uniprot-TrEMBL) AKA SHMT2; Rhea and UniProt confirm the '2' addition, whereas the Blau book chapter only mentions SHMT.
SLC19A1ProteinP41440 (Uniprot-TrEMBL) AKA Folate receptor alpha
SLC46A1ProteinQ96NT5 (Uniprot-TrEMBL) AKA PCFT
THFMetaboliteCHEBI:20506 (ChEBI)
TSProteinP04818 (Uniprot-TrEMBL) AKA TYMS
Vitamin B12MetaboliteCHEBI:30411 (ChEBI)
dTMPMetaboliteCHEBI:17013 (ChEBI)
dUMPMetaboliteCHEBI:17622 (ChEBI)
formaldehydeMetaboliteCHEBI:1684 (ChEBI)
glycineMetaboliteCHEBI:15428 (ChEBI)
iminium ionMetaboliteCHEBI:35286 (ChEBI)
p-amino-benzoyl-polyglutamateMetaboliteReference [PMID:30587505] does not provide info on stereochemistry
qDHFMetaboliteAIZSNLNTIFEHJG-KIYNQFGBSA-N (InChIKey) AKA quinoid DHF; SMILES: Nc1-n=C2NCC(CNc3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N=c2C(=O)N=1
serineMetaboliteCHEBI:17822 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
10-Formyl-THFTHFmim-conversion10181 (Rhea)
5,10-Methenyl-THF5-Formyl-THFmim-conversion10490 (Rhea)
5,10-Methylene-THFmim-conversion12105 (Rhea)
5-Formyl-THF5,10-Methenyl-THFmim-conversion10489 (Rhea)
5-Methyl-THF5-Methyl-THFmim-translocation60461 (Rhea)
THF5,10-Methylene-THFmim-conversion15483 (Rhea)
THFmim-conversion15099 (Rhea)
dTMPmim-conversion12105 (Rhea)
dUMP12105 (Rhea)
glycinemim-conversion15483 (Rhea)
serine15483 (Rhea)
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