Folylpolyglutamate synthase, mitochondrial

Definition:

Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstituted reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.

References:

[1]. C B Osborne, et al. Regulation of folate and one-carbon metabolism in mammalian cells. I. Folate metabolism in Chinese hamster ovary cells expressing Escherichia coli or human folylpoly-gamma-glutamate synthetase activity. J Biol Chem. 1993 Oct 15;268(29):21657-64. [Content Brief]

[2]. K E Lowe, et al. Regulation of folate and one-carbon metabolism in mammalian cells. II. Effect of folylpoly-gamma-glutamate synthetase substrate specificity and level on folate metabolism and folylpoly-gamma-glutamate specificity of metabolic cycles of one-carbon metabolism. J Biol Chem. 1993 Oct 15;268(29):21665-73. [Content Brief]

[3]. L Chen, et al. Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene. J Biol Chem. 1996 May 31;271(22):13077-87. [Content Brief]

[4]. J S Kim, et al. Regulation of folate and one-carbon metabolism in mammalian cells. IV. Role of folylpoly-gamma-glutamate synthetase in methotrexate metabolism and cytotoxicity. J Biol Chem. 1993 Oct 15;268(29):21680-5. [Content Brief]

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