Glutamate decarboxylases

Glutamate decarboxylases (GAD) are enzymes that catalyze the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and CO2. Glutamate decarboxylase uses pyridoxal phosphate as a cofactor. This is the only biochemical pathway for the synthesis of the neurotransmitter GABA. Thus, the main function of glutamate decarboxylase is the synthesis of gamma-aminobutyric acid , the major inhibitory neurotransmitter in the human organism. 2 isoforms of glutamate decarboxylase are known: GAD67 and GAD65. At least two other forms GAD25 and GAD44 without enzyme activity have been discovered in developing brains in embryos. GAD-65 is expressed mainly in pancreatic beta cells, and the GAD-67 isoform is expressed in neurons. GAD25 and GAD44, 2 other glutamate decarboxylases lacking enzyme activities, were detected in developing brains in embryos.

In humans, the glutamate decarboxylase isoforms GAD67 and GAD65 are encoded by the genes GAD1 and GAD2. Mutations in the GAD1 gene lead to spastic tetraplegic cerebral palsy type 1 (CPSQ1).

Anti-GAD antibodies(GADA) are found in type 1 diabetes and in Stiff-Man syndrome .

In diabetes mellitus, GAD-65 binds. They are detectable at the beginning of the disease in 50-70 % of type I diabetics. They are used to distinguish type 2 from type 1 diabetes at an early stage (see also LADA = latent autoimmune diabetes in adults).

Antibodies against GAD-67 are found in Stiff-Man syndrome but not in type I diabetes mellitus.