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Literature summary for 6.3.2.17 extracted from

  • Yamamoto, T.; Shikano, K.; Nanki, T.; Kawai, S.
    Folylpolyglutamate synthase is a major determinant of intracellular methotrexate polyglutamates in patients with rheumatoid arthritis (2016), Sci. Rep., 6, 35615 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.3.2.17

Cloned(Commentary)

Cloned (Comment) Organism
FPGS enzyme genotyping, overview Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information enzyme genotyping, 3 genotypes for 3 SNPs of FPGS, the methotrexate polyglutamates MTXPG3-5/1-2 ratio shows significant differences among these 3 genotypes for 3 different SNPs of FPGS Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate Homo sapiens
-
 ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q05932
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
-
 Homo sapiens ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
 ?

Synonyms

Synonyms Comment Organism
Folylpolyglutamate synthase
-
 Homo sapiens
FPGS
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

General Information

General Information Comment Organism
physiological function enzyme FPGS may have a major role in regulating intracellular polyglutamation of methotrexate (MTX) in rheumatoid arthritis patients receiving low-dose weekly methotrexate therapy. MTX binds to the folate transporter, reduced folate carrier 1, gene SLC19A1, in order to enter target cells. Inside the cells, folylpolyglutamate synthetase (FPGS) converts MTX into MTX polyglutamates (MTXPGs), which show long-term persistence in target cells. Gamma-glutamyl hydrolase (GGH) is involved in removing glutamates from MTXPGs. After MTXPGs are converted back to MTX by GGH, the drug is removed from cells by adenosine triphosphate (ATP)-binding cassette transporters. Tetrahydrofolate is required for DNA synthesis and plays a vital role as an essential coenzyme in various aspects of amino acid metabolism, such as serine-glycine conversion and methionine synthesis. MTXPGs also inhibit aminoimidazole carboxamide ribonucleotide transformylase (ATIC), causing the intracellular accumulation of aminoimidazole carboxamide ribonucleotide, which in turn inhibits adenosine-metabolizing enzymes. Polymorphism of the SLC19A1, FPGS, and GGH genes play a vital role in intracellular metabolism of MTX, overview. Among the enzymes involved in intracellular conversion of MTX to MTXPGs, polymorphisms of the FPGS gene are determinants of the intracellular levels of MTXPGs Homo sapiens