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Pathway: folate polyglutamylation

Biochemical pathways in S. cerevisiae are manually curated and maintained in the YeastPathways database. This page summarizes the genes, enzymes, and metabolites involved in the pathway, along with the curated literature.

Pathway Name
folate polyglutamylation
Pathway ID
PWY3O-20
SGD ID
SGD:S000249740
Genes
ADE3 | DFR1 | MET12 | MET13 | MET7 | MIS1 | SHM1 | SHM2
Chemical Compounds
7,8-dihydropteroate | ADP(3-) | ATP(4-) | L-glutamate(1-) | L-serine zwitterion | NAD(1-) | NADH(2-) | NADP(3-) | NADPH(4-) | dihydrofolate(2-) | formate | glycine zwitterion | hydrogenphosphate | hydron | water

Pathway Diagram

Diagram of the pathway from YeastPathways. Click "View interactive diagram at YeastPathways" for the zoomable, clickable version.

folate polyglutamylation pathway diagram

View interactive diagram at YeastPathways

Pathway Summary

Folates are heterocyclic compounds based on a pteroic acid skeleton conjugated to one or more glutamate molecules. The biologically active form of folate is tetrahydrofolate (THF), whose metabolic derivatives serve as cofactors that carry and chemically activate one-carbon (1C) units at different levels of oxidation (methyl-THF, methylene-THF, etc.) The 1C units carried by these folate cofactors are utilized in one-carbon metabolism for the biosynthesis of various compounds including methionine, thymidylate, and purines. S. cerevisiae and many other microorganisms are able to synthesize tetrahydrofolate de novo, unlike humans who must acquire it from the environment. In the folate biosynthesis pathway, dihydrofolate synthetase (Fol3p in S. cerevisiae) adds an initial glutamate molecule to the p-aminobenzoic acid moiety of 7,8-dihydropteroate to form 7,8-dihydrofolate. This compound is then reduced by dihydrofolate reductase (Dfr1p) to tetrahydrofolate, which can subsequently be converted to a 1C unit-carrying THF derivative. The folates produced in this pathway are subject to further glutamylation by folylpolyglutamate synthetase (Met7p), which catalyzes ATP-dependent extension of the glutamate side chain to yield folate polyglutamates. Polyglutamylation is thought to increase the affinity of intracellular folates for folate-dependent enzymes and prevent their efflux out of cells and organelles. Lending to the importance of polyglutamylation for folate coenzyme function, fol3 null mutants require folinic acid supplementation for growth and met7 null mutants are respiratory-deficient and auxotrophic for methionine.

Genes Involved

Genes whose products participate in this pathway, with their systematic names, EC numbers (where the gene product is an enzyme with an assigned EC number), and the gene's SGD description.

GeneSystematic NameEC NumberDescription
ADE3 YGR204W 1.5.1.5, 3.5.4.9, 6.3.4.3 Cytoplasmic trifunctional enzyme
DFR1 YOR236W 1.5.1.3 Dihydrofolate reductase involved in tetrahydrofolate biosynthesis
MET12 YPL023C 1.5.1.20 Protein with MTHFR activity in vitro
MET13 YGL125W 1.5.1.53 Major isozyme of methylenetetrahydrofolate reductase
MET7 YOR241W 6.3.2.17 Folylpolyglutamate synthetase
MIS1 YBR084W 1.5.1.5, 3.5.4.9, 6.3.4.3 Mitochondrial C1-tetrahydrofolate synthase
SHM1 YBR263W 2.1.2.1 Mitochondrial serine hydroxymethyltransferase
SHM2 YLR058C 2.1.2.1 Cytosolic serine hydroxymethyltransferase

Functional Networks

Functional Networks show how the genes in this pathway work together: a graph linking the pathway to its genes and their shared GO biological-process terms and phenotype observables, and the GO-CAM causal activity models that involve these genes.

Shared Annotations

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GO-CAMs

GO-CAM (Gene Ontology Causal Activity Model) pathway models that involve the genes in this pathway. A gene can participate in more than one model, so use the dropdown to switch between them; the model for this pathway is shown by default.

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GO Enrichment

Gene Ontology biological-process terms enriched among the genes in this pathway, computed with GO Term Finder. Terms are shown with the number of pathway genes annotated to them and the corrected p-value.

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References

List of references used specifically to curate the information on this page.

Resources

YeastPathways