Glutamate--cysteine ligase or gamma-glutamylcysteine synthetase (gamma-GCS) catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine to form L-gamma-glutamyl-L-cysteine, the first and rate-limiting step in glutathione (GSH) biosynthesis []. The enzyme is a heterodimer composed of a catalytic subunit and a regulatory subunit. The catalytic subunit exhibits all of the catalytic activity, but its association with the regulator subunit alters its kinetic properties to enhance activity []. In addition to some conditions which specifically upregulate the catalytic subunit gene, expression of both genes is increased in response to oxidants, heavy metals, phenolic antioxidants, GSH-conjugating agents []and lack of amino acids [].
