Neurotransmitter synthesis

Neurotransmitter synthesis


Serotonin (5-Hydroxytryptamine, 5-HT)

Synthesis

It is made in the CNS in the raphe nuclei (in the brainstem) also in the GI tract (enterochromaffin cells). It is synthesised from the amino acid L-tryptophan which is obtained from the diet. L-tryptophan can cross the blood brain barrier, whereas serotonin cannot. 

Transformation of L-tryptophan into serotonin involves two steps:

  • Hydroxylation to 5-hydroxytryptophan catalysed by tryptophan hydroxylase

  • Followed by decarboxylation of 5-hydroxytryptophan to serotonin (5-hydroxytryptamine) by L-aromatic amino acid decarboxylase


Breakdown

It is taken up from the synapse by a monoamine transporter (SERT). Substances that block this transporter include; MDMA, amphetamine, cocaine, TCA's, and of course SSRI's. It is broken down by MAO and then oddly enough aldehyde dehydogenase to 5-Hydroxyindoleacetic acid (5-HIAA).

Norepinephrine

Synthesis

Norepinephrine is synthesised from tyrosine by the following steps. Tyrosine is firstly converted to L-DOPA by tyrosine hydroxylase. L-DOPA is then converted to dopamine by DOPA decarboxylase. Dopamine is then converted to norepinephrine by dopamine beta-hydroxylase. Norepinephrine is then converted to epinephrine by phenylethanolamine-N-methyltransferase.

Release

The main site of norepinephrine release is from the locus coeruleus (aka 'the blue spot) which is located in the pons.

Breakdown

It is broken down by both COMT (catechol-O-methyl transferase) and MAO (monoamine oxidase).

Histamine 

Histamine is produced from the amino acid histidine by a histidine decarboxylase and is metabolised by the combined actions of histamine methyltransferase and MAO.