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 Hu

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Diseases Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Pathway Ontology

folate metabolic pathway methylenetetrahydrofolate reductase deficiency pathway disease pathway

Disease Ontology

vitamin B12 deficiency vitamin metabolic disorder megaloblastic anemia cerebral folate receptor alpha deficiency glutamate formiminotransferase deficiency

Cell Type Ontology

central nervous system neuron

Participants

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
Folic acid Metabolite chebi:27470
THF Metabolite chebi:20506
5-Methyl-THF Metabolite chebi:15641
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
MTHFD1 Protein uniprot:P11586
SHMT1 Protein uniprot:P34896
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

  1. 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
  2. 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