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Differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation.


ABSTRACT: GCL (glutamate-cysteine ligase) is a heterodimer of a GCLC (GCL catalytic subunit) that possesses all of the enzymatic activity and a GCLM (GCL modifier subunit) that alters the K(i) of GCLC for GSH. We hypothesized that the expression of GCLM and the association of GCLM with GCLC were responsible for the apparent increase in GCL activity state observed in the liver of rats fed low-protein diets or in hepatocytes cultured in low-sulphur amino acid-containing medium. Therefore we conducted a series of studies using rats and a human hepatoma (HepG2/C3A) cell line to assess the role of GCLM and holoenzyme formation in the regulation of GCL activity in response to sulphur amino acid intake or availability. Increases in GCL activity in rat liver, as well as in HepG2 cells, were due to the addit

SUBMITTER: Lee JI 

PROVIDER: S-EPMC1383676 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature