Brain Glutamate Decarboxylase

Glutamate decarboxylase (glutamate 1-carboxylyase, EC 4.1.1.15, GAD)* IS the major, rate-limiting enzyme in brain for synthesizing gamma-aminobutyric acid (GABA). Total GAD activity in brain is 10-20 times greater than the observed rate of GABA synthesis (Collins, 1972; Matsui and Deguchi, 1977; Casu and Gale, 1981), indicating that GAD operates at only a fraction of its capacity. Although other routes of synthesis have been suggested, they appear to be minor (Baxter, 1976). GAD has a distinct regional distribution in brain that parallels the regional distribution of GABA (Collins, 1972; Fahn, 1976), as would be expected of a rate-Limiting biosynthetic enzyme. Because GAD appears to be the major biosynthetic enzyme for GABA, it is used as one of the principal markers for GABA neurons and presynaptic terminals; it does not appear to be present in appreciable amounts in glial cells (Schousboe et al., 1977; Wu et al., 1979). GAD is concentratedin the presynaptic endings of GABA neurons, but is also present in the cell bodies, as shown by subcellular fractionation (Salganicoff and DeRobertis, 1965; Van Kempen et al., 1965; Fonnum, 1968) and by immunocytochemistry (Saito et al., 1974; Wood et al., 1976; Ribak et al., 1978; Oertel et al., 1981c). Lesioning and immunocytochemical studies using GAD as a marker have provided evidence of long-axon, GABA neurons that project between brain regions. For example, GAD-containing Purkinje cells project from cerebellar cortex to deep cerebellar nuclei