Abstract
Folypolyglutamate synthetase(FPGS) catalyzes the addition of multiple glutamate molecules to compounds with the basic pteroylglutamate structure,such as polyglutamylation-dependent novel antifolates.As the antifolates like methotrexate require polyglutamation by FPGS for activation,FPGS has an established position in the cytotoxic action of methotrexate and has become a essential part in methotrexate resistance.Recent studies have indicated that decreased mRNA expression and activity of FPGS can cause reduction of methotrexate-polyglutamates accumulation,which have been observed as a dominant mechanism leading to methotrexate resistance.Furthermore,single nucleotide polymorphism in FPGS has been displayed significant associations with methotrexate sensitivity and susceptibility of deseases,though the detail mechanism is unknown.This paper is to review the relationship among FPGS enzyme activity,gene polymorphism and methotrexate drug sensitivity. Key words: Folypolyglutamate synthetase; Methotrexate; Drug sensitivity
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