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The first step is catalyzed by glutamate-cysteine ligase (GCL), which is composed of catalytic and modifier subunits (GCLC and GCLM)

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Because the hinge and latch hypothesis predicts that the wild-type-mutant heterodimer does not support Nrf2 ubiquitination, a heterozygous missense mutation would result in the 75% reduction of Keap1 activity