Disorders of folate metabolism and transport (WP4259)
Homo sapiens
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 [https://www.wikipathways.org/index.php/Pathway:WP4288].
Authors
Jesse Vercoulen , Egon Willighagen , Andra Waagmeester , Denise Slenter , Kristina Hanspers , Irene Hemel , Josien Landman , Friederike Ehrhart , Eric Weitz , and Finterly HuActivity
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Organisms
Homo sapiensCommunities
Diseases Inherited Metabolic Disorders (IMD) Pathways Rare DiseasesAnnotations
Pathway Ontology
folate metabolic pathway methylenetetrahydrofolate reductase deficiency pathway disease pathwayDisease Ontology
vitamin B12 deficiency vitamin metabolic disorder megaloblastic anemia cerebral folate receptor alpha deficiency glutamate formiminotransferase deficiencyCell Type Ontology
central nervous system neuron| Label | Type | Compact URI | Comment |
|---|---|---|---|
| SAM | Metabolite | chebi:67040 | |
| serine | Metabolite | chebi:17822 | |
| THF | Metabolite | chebi:20506 | |
| 5-Methyl-THF | Metabolite | chebi:15641 | |
| NH4+ | Metabolite | chebi:28938 | |
| L-glutamic acid | Metabolite | chebi:16015 | |
| SAH | Metabolite | chebi:16680 | |
| CO2 | Metabolite | chebi:16526 | |
| glycine | Metabolite | chebi:15428 | |
| N-formimidoyl-L-glutamate | Metabolite | chebi:58928 | Based on Rhea, the side metabolite is not Histidine |
| Homocysteine | Metabolite | chebi:17230 | |
| DHF | Metabolite | chebi:15633 | AKA 7,8-DHF |
| Methionine | Metabolite | chebi:16643 | |
| Folic acid | Metabolite | chebi:27470 | |
| 5,10-Methylene-THF | Metabolite | chebi:1989 | |
| Vitamin B12 | Metabolite | chebi:30411 | |
| 5-formimino-THF | Metabolite | chebi:15639 | |
| 5,10-Methenyl-THF | Metabolite | chebi:15638 | |
| GAR | Metabolite | chebi:18349 | |
| Formyl-GAR | Metabolite | chebi:18272 | |
| AICAR | Metabolite | chebi:2030 | |
| FAICAR | Metabolite | chebi:18381 | |
| 10-Formyl-THF | Metabolite | chebi:15637 | |
| 5-Formyl-THF | Metabolite | chebi:15640 | |
| dTMP | Metabolite | chebi:17013 | |
| dUMP | Metabolite | chebi:17622 | |
| qDHF | Metabolite | wikidata:Q117085463 | 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 |
| 7.8-dihydropterin | Metabolite | chebi:64277 | Reference [PMID:30587505] does not provide info on stereochemistry |
| iminium ion | Metabolite | chebi:35286 | |
| formaldehyde | Metabolite | chebi:1684 | |
| MTHFD1 | Protein | uniprot:P11586 | Found based on EC code for MTHFCH, information in UniProt describes this reaction. |
| QDPR | Protein | uniprot:P09417 | |
| MTHFD1 | Protein | uniprot:P11586 | |
| SHMT1 | Protein | uniprot:P34896 | |
| GARTF | Protein | uniprot:C9JKQ7 | |
| MTHFS | Protein | ensembl:ENSG00000136371 | |
| MTHFCH | Protein | eccode:3.5.4.9 | MTHFCH: methenyl-THF cyclohydrolase |
| SLC46A1 | Protein | uniprot:Q96NT5 | AKA PCFT |
| FOLR1 | Protein | uniprot:P15328 | AKA Folate receptor alpha |
| AICART | Protein | uniprot:P31939 | AKA ATIC, PURH |
| TS | Protein | uniprot:P04818 | AKA TYMS |
| ALDH1L1 | Protein | uniprot:O75891 | AKA FTHFD, cytosolic |
| MS | Protein | uniprot:Q99707 | |
| SHMT | Protein | uniprot:P34897 | AKA SHMT2; Rhea and UniProt confirm the '2' addition, whereas the Blau book chapter only mentions SHMT. |
| FTCD | Protein | uniprot:O95954 | AKA FITHFCH |
| DHFR | Protein | uniprot:B0YJ76 | |
| MTHFR | Protein | uniprot:P42898 | |
| SLC19A1 | Protein | uniprot:P41440 | AKA Folate receptor alpha |
| ALDH1L2 | Protein | uniprot:Q3SY69 | AKA FTHFD, mitochondrial |
| MTHFD2 | Protein | uniprot:P13995 | Found based on EC code for MTHFCH, information in UniProt describes this reaction. |
| MTHFD2L | Protein | uniprot:Q9H903 | Found based on EC code for MTHFCH, information in UniProt describes this reaction. |
References
- Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
- Toward a better understanding of folate metabolism in health and disease. Zheng Y, Cantley LC. J Exp Med. 2019 Feb 4;216(2):253–66. PubMed Europe PMC Scholia