Phosphate-activated glutaminase, also known as Glutaminase 2 (GLS2), was initially isolated from rat liver, although it has been shown to be expressed in other tissues. Like the functionally similar, larger kidney glutaminase, GLS2 catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Expression of GLS2 is increased by p53 under both stressed and nonstressed conditions, resulting in increased levels of glutamate and alpha-ketoglutarate, which in turn results in enhanced mitochondrial respiration and ATP generation. GLS2 also regulates antioxidant defense function in cells by increasing reduced glutathione levels and decreasing ROS-levels, suggesting that GLS2 acts as a mediator of p53’s role in antioxidant defense in addition to its role in energy metabolism.
