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 Biosynthesis of Neurotransmitters

Neurotransmitters are compounds that relay, amplify or modulate electric signals across neural and neuromuscular synapses, between neurons or neurons and muscle cells, respectively. Neurotransmitters are synthesized within pre-synaptic neurons. Upon stimulation of the pre-synaptic neuron, neurotransmitters cross the synaptic space, bind to post-synaptic cell receptors, induce an effect in the post-synaptic cell and become inactivated. The net effect is cell to cell specific conveyance of an electric impulse to induce an effect.

Amino acids are especially important compounds in the evolution of neurotransmitters. Some amino acids including the alpha amino acids; L-aspartate (ASP), L-glutamate (GLU) and glycine (GLY); and the gamma amino acid, γ-aminobutyric acid (GABA), are neurotransmitters. Glutamate is decarboxylated to GABA by Glutamate Decarboxylase (EC 4.1.1.15). Amino acids are also precursors of several monoamine neurotransmitters including Histamine, Serotonin and the catecholamines; Dopamine (DA), Norepinephrine (NE) and Epinephrine (Epi) (Adrenaline).

L-Histidine is decarboxylated to Histamine by Histidine Decarboxylase (EC 4.1.1.22). Serotonin is derived from L-Tryptophan by a two step enzymatic process. L-Tryptophan is first converted to 5-Hydroxytryptophan by L-Tryptophan Hydroxylase (tryptophan 5-monooxygenase, EC 1.14.16.4) and then to Serotonin by Aromatic L-Amino Acid Decarboxylase (EC 4.1.1.28). This enzyme also decarboxylates L-DOPA, the catechol amino acid formed from L-Tyrosine, to Dopamine in the first step of monoamine catechol neurotransmitters biosynthesis. Catechol neurotransmitter biosynthesis is initiated by L-Tyrosine Hydroxylase (EC 1.14.16.2) which hydroxylates L-Tyrosine to form L-DOPA. Norepinephrine and Epinephrine are synthesized from Dopamine by sequential hydroxylation and methylation reactions. Dopamine β-Hydroxylase (dopamine β-monooxygenase, EC 1.14.17.1) converts Dopamine into Norepinephrine which is then methylated by Phenylethanolamine N-Methyltransferase (noradrenaline N-methyltransferase, EC 2.1.1.28) to form Epinephrine.