Folylpolyglutamate synthase, mitochondrial (FPGS)

Folylpolyglutamate synthase, mitochondrial is an enzyme encoded by the FPGS gene. It catalyzes the ATP-dependent addition of glutamate residues to folate and its derivatives, converting them into polyglutamated forms. This modification allows for efficient cellular retention of folates and supports their function as essential cofactors for one-carbon transfer reactions required in nucleotide biosynthesis and amino acid metabolism. The enzyme plays a central role in maintaining both cytosolic and mitochondrial pools of folylpolyglutamates, which is critical for cell proliferation and survival. It also metabolizes antifolate drugs like methotrexate into active polyglutamated forms that inhibit key enzymes involved in DNA synthesis.

Other names

Folylpolyglutamate synthetaseFPGS proteinTetrahydrofolylpolyglutamate synthaseFOLC protein

Drugs such as methotrexate act as antifolates; their efficacy depends on polyglutamation by folylpolyglutamate synthase for intracellular retention and activity against folate-dependent enzymes involved in DNA synthesis.