Folylpolyglutamate synthase: Difference between revisions
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== Function == | == Function == | ||
FPGS is active in intracellular folate homeostasis. Polyglutamated folates are substrates for generation of the primary metyhl group donor S-adenosylmethionine (SAM)<ref>PMID:26895662</ref>, among others. The FPGS enzyme catalyzes formation of an amide bond between the amino group of glutamate and the gamma carboxylate group of tetrahydrofolate (which contains a single glutamate unit) or of the free gamma carboxylate of the glumatamyl tail of polyglutamyl tetrahydrofolate. This reaction requires ATP, | FPGS is active in intracellular folate homeostasis. Polyglutamated folates are substrates for generation of the primary metyhl group donor S-adenosylmethionine (SAM)<ref>PMID:26895662</ref>, among others. The FPGS enzyme catalyzes formation of an amide bond between the amino group of glutamate and the gamma carboxylate group of tetrahydrofolate (which contains a single glutamate unit) or of the free gamma carboxylate of the glumatamyl tail of polyglutamyl tetrahydrofolate. This reaction requires ATP; before the amide bond forms, the carboxylate reacts with ATP to form a phosphate ester intermediate and ADP. In the second step, phosphate is the leaving group as the amide bond forms. The deconjugation reaction (i.e. removing glutamate units) is catalyzed by a hydrolase (folate gamma-glutamyl hydrolase, or GGH) and proceeds independent of ATP. Apart from reacting with various folates, FPGS also acts on anti-folates (competitive inhibitores of enzymes that act of folates). The polyglutaminylation of anti-folates makes them effective inhibitors. | ||
[[Image:Tetrahydrofolate synthase hydrolase.PNG|600px]] | [[Image:Tetrahydrofolate synthase hydrolase.PNG|600px]] | ||