Originally, two isoforms were described for GLase, the brain/kidney-type and the liver type (Aledo et al., 2; Nagase et al., 36), but GLase is expressed in most tissues in an organ-specific pattern. Tissue-associated alternative RNA splicing yields two 2.4- to 4.8-kb mRNA species and protein isoforms with molecular masses of 58 to 75 kDa (Elgadi et al., 11; Labow et al., 27; Perez-Gomez et al., 40; Turner and McGivan, 52). Liver GLase expression up-regulates in response to starvation, diabetes, or heightened amino acid catabolism following high protein load (Watford et al., 54,56; Labow et al., 27). This up-regulation appears to support gluconeogenesis and delivers precursors to the urea cycle (Nurjhan et al., 39; Stumvoll et al., 48; Watford et al., 56). Hepatic GLase expression responds to high-glucagon/low-insulin ratios and cAMP stimuli (Häussinger et al., 19; McGivan et al., 33), the latter linked to a cAMP-responsive element in its promoter (Chung-Bok et al., 7). Kidney GLase is induced by metabolic acidosis (Watford, 55); increased expression derives from selective mRNA stabilization by a pH-responsive element (Laterza et al., 28,29; Curthoys, 8; Porter et al., 41). In brain, 70 percent of glutamate is produced by GLase, the remaining 30 percent being derived from de novo synthesis (Hertz, 22). Using platelets, a strong genetic component on catalytic activity of GLase with a high correlation coefficient of up to 0.96 was demonstrated in a twin study (Sahai and Vogel, 43).
GLase is a mitochondrial enzyme with soluble and membrane-associated forms; however, intact mitochondria appear to contain active GLase externally in the inner mitochondrial membrane and an inactive pool within the mitochondrium (Kvamme et al., 26).