Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that catalyzes the decarboxylation of glutamate to GABA

Gabâ

Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...

 and CO₂. GAD uses PLP

Pyridoxal-phosphate

Pyridoxal-phosphate is a prosthetic group of some enzymes. It is the active form of vitamin B6, which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine.-Role as a coenzyme:...

 as a cofactor

Cofactor (biochemistry)

A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

. The reaction proceeds as follows:

HOOC-CH₂-CH₂-CH(NH₂)-COOH → CO₂ + HOOC-CH₂-CH₂-CH₂NH₂

In mammals, GAD exists in two isoforms encoded by two different gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s - GAD1

GAD1

Glutamate decarboxylase 1 , also known as GAD1, is a human gene.This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from...

 and GAD2

GAD2

Glutamate decarboxylase 2 is an enzyme that in humans is encoded by the GAD2 gene.This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of...

. These isoforms are GAD₆₇ and GAD₆₅ with molecular weights of 67 and 65 kDa

KDA

KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...

, respectively. GAD1 and GAD2 are expressed in the brain where GABA is used as a neurotransmitter

Neurotransmitter

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

, GAD2 is also expressed in the pancreas.

At least two more forms, GAD25 and GAD44 (embryonic; EGAD) are described in the developing brain. They are coded by the alternative transcripts of GAD1, I-80 and I-86: GAD25 is coded by both, GAD44 - only by I-80.

Diabetes

Both GAD₆₇ and GAD₆₅ are targets of autoantibodies

Autoantibody

An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...

 in people who later develop type 1 diabetes mellitus

Diabetes mellitus

Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

 or latent autoimmune diabetes

Latent autoimmune diabetes

Latent Autoimmune Diabetes of Adults , also known as, Diabetes Type 1.5, is a term coined by Tuomi et al. in 1993 to describe slow-onset Type 1 autoimmune diabetes in adults...

. Injections with GAD₆₅ has been shown to preserve some insulin production for 30 months in humans with type 1 diabetes.

Schizophrenia and bipolar disorder

Substantial dysregulation of GAD mRNA expression, coupled with downregulation of reelin

Reelin

Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...

, is observed in schizophrenia

Schizophrenia

Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

 and bipolar disorder

Bipolar disorder

Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

. The most pronounced downregulation of GAD67 was found in hippocampal stratum oriens layer in both disorders and in other layers and structures of hippocampus with varying degrees.

Parkinson disease

The bilateral delivery of glutamic acid decarboxylase (GAD) by an adeno-associated viral vector into the subthalamic nucleus of patients between 30 and 75 years of age with advanced, progressive, levodopa-responsive Parkinson disease resulted in significant improvement over baseline during the course of a six-month study.

Cerebellar disorders

Intracerebellar administration of GAD autoantibodies to animals increase the excitability of motoneurons and impairs the production of nitric oxide (NO), a molecule involved in learning. Epitope recognition contributes to cerebellar involvement.

Alteration by drugs

Pregabalin

Pregabalin

Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in the European Union. It was designed...

, an antiepileptic drug, increases neuronal GABA levels by producing a dose-dependent increase in glutamic acid decarboxylase activity.http://www.tapi.com/tapiteva/productPages/Pregabalin
Extracts from Centella asiatica

Centella asiatica

Centella asiatica is a small herbaceous annual plant of the family Mackinlayaceae or subfamily Mackinlayoideae of family Apiaceae, and is native to India, Sri Lanka, northern Australia, Indonesia, Iran, Malaysia, Melanesia, Papua New Guinea, and other parts of Asia...

 (gotu kola) and Valeriana officinalis (valerian) stimulated GAD activity.

External links

• Genetics, Expression Profiling Support GABA Deficits in Schizophrenia - Schizophrenia Research Forum, 25 June 2007.