Relationship between folypolyglutamate synthetase and methotrexate drug sensitivity

VernacularTitle:叶酰多聚谷氨酸合成酶与甲氨蝶呤敏感性的关系
Author: Chunyan HU
Publication Type:Journal Article
Keywords: Folypolyglutamate synthetase; Methotrexate; Drug sensitivity
From: International Journal of Pediatrics 2012;39(2):183-186
CountryChina
Language:Chinese
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.