Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels

Y Chen, HG Shertzer, SN Schneider, DW Nebert… - Journal of Biological …, 2005 - jbc.org
Glutamate cysteine ligase (GCL), which synthesizes γ-glutamyl-cysteine (γ-GC), is the rate-
limiting enzyme in GSH biosynthesis. γ-GC may be produced by the catalytic subunit GCLC
or by the holoenzyme (GCLholo), which comprises GCLC and the modifier subunit GCLM.
The Gclm (–/–) knock-out mouse shows tissue levels of GSH that are between 9 and 40% of
the Gclm (+/+) wild-type mouse. In the present study, we used recombinant GCLC and
GCLM and Gclm (–/–) mice to examine the role of GCLM on γ-GC synthesis by GCLholo …