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Monoamine Sythesis, Storage and Degradation

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  1. Introduction
  2. Serotonin
  3. Catecholamines
  4. Histamine
  5. Acetylcholine
  6. Plasma membrane transporters
  7. Vesicular monoamine transporter
  8. References

In addition to similarities in neuronal organization, monoaminergic systems are similar with regard to their synthesis, storage, and degradation. Monoamines are synthesized within neurons from common amino acid precursors and taken up into synaptic vesicles via a vesicular monoamine transporter. Upon stimulation, vesicles within nerve terminals release neurotransmitter into the synaptic cleft. Once released, the monoamines interact with postsynaptic receptors to alter the excitability of postsynaptic cells. Monoamines may also interact with presynaptic autoreceptors located on the nerve terminal to suppress further release. In addition, released monoamines may be taken back up from the synaptic cleft into the nerve terminal by plasma membrane transporter proteins. Reuptake plays an important role in limiting the magnitude and duration of action of synaptically released monoamines. Once monoamines are taken up, they may be subject to enzymatic degradation or they may be protected from degradation by uptake into vesicles. The processing of acetylcholine differs from this scheme, and is described below.

[...] Two enzymes that play major roles in the degradation of catecholamines are monoamine oxidase and catechol O-methyltransferase (COMT). Monoamine oxidase is located on the outer membrane of mitochondria and oxidatively deaminates catecholamines to their corresponding aldehydes. Two MAO isozymes with differing substrate specificities have been identified: MAOA, which preferentially deaminates serotonin and norepinephrine, and MAO type B (MAOB), which deaminates dopamine, histamine, and a broad spectrum of phenylethylamines. The blockade of monoamine catabolism by MAOIs produces elevations in brain monoamine levels. [...]

[...] The first step in the degradation of serotonin is mediated by monoamine oxidase (MAO) type A. A (MAOA), which oxidizes the amino group to form an aldehyde. MAOA is located in mitochondrial membranes and is nonspecific in its substrate specificity; in addition to serotonin, it oxidizes norepinephrine. The elevation of serotonin levels by MAO inhibitors (MAOIs) is believed to underlie the antidepressant efficacy of these drugs. Following oxidation by MAOA, the resulting aldehyde is further oxidized to 5-hydroxyindoleacetic acid (5-HIAA). [...]

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