Glutamate decarboxylase

Glutamate decarboxylase
	GAD67 according to PDB 2okj
	Existing structural data : 2okj , 2okk
Mass / length primary structure	594/585 amino acids
Secondary to quaternary structure	Homodimer
Cofactor	Pyridoxal phosphate
Isoforms	GAD25, GAD65, GAD67
Identifier
Gene name (s)	GAD1 , GAD2
External IDs	OMIM : 605363 ; UniProt : Q99259 ;
Enzyme classification
EC, category	4.1.1.15 , lyase
Response type	Decarboxylation
Substrate	L -glutamate
Products	γ-aminobutyrate + CO 2
Occurrence
Parent taxon	Eukaryotes

Glutamate decarboxylase (GAD) is an enzyme in eukaryotes , comprising the decarboxylation of glutamate to γ-aminobutyric acid (GABA) and CO ₂ catalyzed . This is the only way to biosynthesize the neurotransmitter GABA. As a co-factor glutamate decarboxylase used pyridoxal phosphate . Two genes are known in humans that code for enzymes with this activity: GAD1 and GAD2 . Mutations in the GAD1 gene can lead to enzyme deficiency in the brain, which leads to spastic tetraplegic cerebral palsy type 1 (CPSQ1).

In mammals , glutamate decarboxylase exists in two isoforms, GAD67 and GAD65, which are encoded by the two genes GAD1 and GAD2 . Both genes are in cells in the brain expressed . In addition, GAD2 is also expressed in the pancreas . At least two other forms GAD25 and GAD44 without enzyme activity have been discovered in developing brains in embryos.

Catalyzed reaction

${\ displaystyle \ longrightarrow}$ CO ₂ +

Glutamate is decarboxylated to GABA. Further substrates of the isoform in the brain: L - cysteate , 3-sulfino- L- alanine and L - aspartic acid .

Antibodies against GAD

Glutamate decarboxylase antibodies against isoform 65 are detectable in 50–70% of type I diabetics at the onset of the disease . Especially in adults with newly developed diabetes , they are used to differentiate between type 2 and type 1 diabetes at an early stage. (see also LADA = latent autoimmune diabetes in adults.)