Gamma-Aminobutyric acid

• 4-aminobutyric acid
• 4- aminobutyric acid
• Piperidinsäure
• γ - aminobutyric acid
• γ - aminobutyrate
• GABA

Colorless solid

Fixed

203 ° C ( decomposition)

4.05

Very well in water (1300 g · l-1 at 25 ° C)

Attention

12,680 mg · kg -1 ( LD50, mouse, oral)

Template: Infobox chemical / molecular formula search available

The γ -aminobutyric acid (GABA, from the English gamma -aminobutyric acid) is the biogenic amine of the glutamic acid, an amine, the acid and the major inhibitory ( inhibiting) a neurotransmitter in the central nervous system. Chemically it is a non-protein amino acid structurally. Of the proteinogenic (ie occurring in proteins ) α -amino acids distinguishes itself in the position of the amino group relative to the carboxyl group: GABA is a γ - amino acid, as the amino group is in at the carboxyl carbon atom at the third carbon atom. At the α -amino acids found in proteins, the amino group, however, is on the adjacent carbon atom to the carboxyl carbon.

Receptors

GABA binds to specific receptors. There are ionotropic and metabotropic GABA receptors:

• The GABAA receptor is a ligand-gated chloride ion channel ( ionotropic ), which opens and an inhibitory signal triggers when GABA binds to it.
• The GABAA receptor ρ, once called GABAC receptor, is a ionotropic receptor. It differs from the GABAA receptor in that it is composed of ρ subunits and many pharmacological substances such as benzodiazepines and barbiturates at this receptor are ineffective.
• The GABAB receptor belongs to the G protein- coupled receptors ( metabotropic ). He confers an increased open probability of potassium channels. This leads to hyperpolarization of the cell membrane. Furthermore, the open probability of calcium channels is reduced. This effect is mainly presynaptic noticeable here the transmitter secretion is inhibited.

Biosynthesis and metabolism

GABA is produced by the glutamate decarboxylase ( GAD) from glutamate. In a step is therefore produced from the major excitatory neurotransmitter of the major inhibitory.

CO2

GABA is transported partly in neighboring glial cells. There, it is converted to succinate semialdehyde by GABA transaminase and thus can be introduced and degraded in the citric acid cycle.

GABA receptors are commonly found in the pre-synaptic cell, which leads to a presynaptic inhibition. The GABA can be taken up in either the pre-synaptic cell and stored in vesicles metabolized by the GABA - transaminase, or further processed in the Glutaminzyklus in glial cells after their use.

GABA receptors play an important role in brain development. Interestingly, GABA acts in the fetus excitatory and is essential for the establishment of neural connections.

Role of GABA in the pancreas

GABA is known as an inhibitory neurotransmitter. In various endocrine cells GABA inhibits hormone secretion by hyperpolarizing the cell membrane. Significant effect in the pancreas, inhibition of glucagon secretion of the alpha cells of the islets of Langerhans.

Synthesis and secretion of

In the insulin- forming beta cell islets of Langerhans of the pancreas arises from GABA glutamate by the enzyme GAD65 ( glutamate decarboxylase ) and the isoform GAD67. The beta cell secretes GABA on three systems: over SLMV ( synaptic -like microvesicles, synaptic vesicles are similar ), over a small part of the LDCV (large dense core vesicles that contain the insulin -zinc complex ), and probably also on ( non-specific? ) transport systems of the plasma membrane for organic acids and amino acids.

The respective vesicles have a GABA transporter ( VIAAT / VGAT ) and a vacuolar H -ATPase, which builds an electrochemical gradient by proton transport in the granule into ( acidification ) and thus forms the drive for loading the granule.

Regulation

The GABA secretion is initially constitutively ( every four hours is the total stock secreted ). In addition, the vesicular secretion, which is similar to that of insulin regulated by calcium influx occurs (10% of LDCV Insulingranulen contain GABA, the SLMV are also secreted in a calcium influx through ). The amount of GABA is secretable including through cAMP / PKA regulated ( stimulation of the system eg by glucagon-like peptide 1 ( GLP1 ) ) by GAD67 is induced, and all physiological concepts contrary tends to reduce glucose because GABA is metabolized via the GABA shunt in the mitochondria. The limiting enzyme GABA transaminase is the GABA -T.

Effect

The secreted GABA is located in the cell gap and by diffusion or via the regular capillary flow to the island coat. There, she reached the glucagonproduzierenden alpha cells. These feature a ionotropic GABAA receptor. The activation of which causes a chloride influx and the hyperpolarization of the plasma membrane, and thus the inhibition of glucagon secretion.

Physiology

An old concept states that glucose inhibits glucagon secretion. A case relevant principle is that the number of GABAA receptor is increased in the alpha cells by glucose. GABA is in high concentration ( constitutionally ) available. About 30 % of the glucose effect thus can be explained by GABA. GABA has on the beta cell does not receptor-mediated effect; somatostatin delta cell is also inhibited.

Clinical Perspective

You try to explain the increased Glucagonbildung of the diabetic by a deficiency of GABA ( by lack of synthesis in the absence or exhausted beta cells). There is the idea of ​​a mediated by the GABAA receptor suppression of the activity of T lymphocytes.