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½Å°æÀü´Þ ¹°Áú : ¥ã-Aminobutyric acid (GABA)

½Å°æÀü´Þ¹°Áú : ½Å°æÀü´Þ¹°Áú Á¾·ù
- ±Û·çŽ»êÀÇ ¿ªÇÒ Glu : ÈïºÐ
- ¿îµ¿ : ¾Æ¼¼Æ¿Äݸ°, ´ÏÄÚƾ »ý¸®ÀÛ¿ë
- ÈïºÐ : Glu, Aspartate, ±Û¸®½Å
- ¾ïÁ¦ : GABA
- °¨Á¤ : Æ®¸³ÅäÆÇ - ¼¼·ÎÅä´Ñ, ¸á¶óÅä´Ñ
- °¨Á¤ : Ƽ·Î½Å - µµÆĹÎ, ³ë¸£¾Æµå³×³¯¸°, ¾Æµå³×³¯¸°



 



ºê·¹ÀÌÅ© Àû¿ë : chief inhibitory neurotransmitter in the mammalian central nervous system.
   ´º·ÐÀÇ 1¸¸°³ ½Ã³À½ºÁß 8000°³ Á¤µµ°¡ glutamic acid ¼ö¿ëü, 2000°³ gaba ¼ö¿ëü

GABAÀÇ ½Å°æ Àü´Þ ¹°Áú°ú ¼ö¿ëü´Â ´Ù¾çÇÑ ³ú ±â´É¿¡ °ü¿©ÇÏ°í ÀÖ½À´Ï´Ù. GABAÀÇ ºÒ±ÕÇüÀº ¶ÇÇÑ ¾ç±Ø¼º Àå¾Ö, Á¤½Å ºÐ¿­Áõ, ±×¸®°í ºÒ¾È Àå¾Ö¿Í °ü·ÃÀÌ ÀÖ´Ù. GABAÀÇ ÁÖ¿ä ±â´ÉÀº ½Å°æ¼¼Æ÷ÀÇ ¹ßÈ­ ¾ïÁ¦À̱⠶§¹®¿¡ GABA´Â ½Åü¸¦ ¡®¾ÈÁ¤½ÃÅ°´Â¡¯ Áö½Ã¿¡¼­ Áß¿äÇÑ ¿ªÇÒÀ» ´ã´çÇÑ´Ù.µû¶ó¼­ GABA½Ã½ºÅÛÀº °úµµÇÑ ÀÚ±ØÀ¸·ÎºÎÅÍ ³ú¸¦ º¸È£ÇÏ´Â ÀÏÁ¾ÀÇ Á¤º¸ ÇÊÅÍ ¿ªÇÒÀ» ÇÑ´Ù.

In vertebrates, GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neuronal processes. This binding causes the opening of ion channels to allow the flow of either negatively charged chloride ions into the cell or positively charged potassium ions out of the cell. Depending on which ion channels open, the membrane potential is either hyperpolarized or depolarized. This action results in a negative change in the transmembrane potential, usually causing hyperpolarization. Two general classes of GABA receptor are known: GABAA in which the receptor is part of a ligand-gated ion channel complex, and GABAB metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via intermediaries (G proteins).

The production, release, action and degradation of GABA at a stereotyped GABAergic synapseNeurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. Medium Spiny Cells are a typical example of inhibitory CNS GABAergic cells. In contrast, GABA exhibits excitatory actions in insects, mediating muscle activation at synapses between nerves and muscle cells, and also the stimulation of certain glands. In mammals, some GABAergic neurons, such as chandelier cells, are also able to excite their glutamatergic counterparts.[2]

GABA receptors are chloride channels; that is, when activated by GABA, they allow the flow of chloride ions across the membrane of the cell. Whether this chloride flow is excitatory/depolarizing (makes the voltage across the cell's membrane less negative), shunting (has no effect on the cell's membrane) or inhibitory/hyperpolarizing (makes the cell's membrane more negative) depends on the direction of the flow of chloride. When net chloride flows out of the cell, GABA is excitatory or depolarizing; when the net chloride flows into the cell, GABA is inhibitory or hyperpolarizing. When the net flow of chloride is close to zero, the action of GABA is shunting. Shunting inhibition has no direct effect on the membrane potential of the cell, however it minimises the effect of any coincident synaptic input essentially by reducing the electrical resistance of the cell's membrane (essentially equivalent to Ohm's law). A developmental switch in the molecular machinery controlling concentration of chloride inside the cell and hence the direction of this ion flow, is responsible for the changes in the functional role of GABA between the neonatal and adult stages. That is to say, GABA's role changes from excitatory to inhibitory as the brain develops into adulthood.[3]

Structure and conformation
GABA is found mostly as a zwitterion, that is, with the carboxy group deprotonated and the amino group protonated. Its conformation depends on its environment. In the gas phase, a highly folded conformation is strongly favored because of the electrostatic attraction between the two functional groups. The stabilization is about 50 kcal/mol, according to quantum chemistry calculations. In the solid state, a more extended conformation is found, with a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is due to the packing interactions with the neighboring molecules. In solution, five different conformations, some folded and some extended are found as a result of solvation effects. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better.

Synthesis
Since GABA does not penetrate the blood brain barrier, GABA is therefore synthesized in vivo. It is synthesized from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate (which is the active form of vitamin B6) as a cofactor via a metabolic pathway called the GABA shunt. This process converts glutamate, the principal excitatory neurotransmitter, into the principal inhibitory neurotransmitter (GABA)



 


 




 


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