Tryptophan decarboxylase transport

FIGURE 5—34. Serotonin (5-hydroxytryptamine [5HT ) is produced from enzymes after the amino acid precursor tryptophan is transported into the serotonin neuron. The tryptophan transport pump is distinct from the serotonin transporter (see Fig. 5—35). Once transported into the serotonin neuron, tryptophan is converted into 5-hydroxytryptophan (5HTP) by the enzyme tryptophan hydroxylase (TryOH) which is then converted into 5HT by the enzyme aromatic amino acid decarboxylase (AAADC). Serotonin is then stored in synaptic vesicles, where it stays until released by a neuronal impulse. 

Serotonin or 5-hydroxytryptamine (5-HT), a monoamine, is widely distributed in many cells of the body and about 1-2% of the entire serotonin body content is found in the CNS. Serotonin is synthesized by the enzyme amino acid decarboxylase from 5-hydroxytryptophan (which is derived from tryptophan via tryptophan hydroxylase). The rate-limiting step is the production of 5-hydroxytryptophan by tryptophan hydroxylase. Serotonin is removed from the synapse by a high-affinity serotonin uptake site that is capable of transporting serotonin in either direction, depending on the concentration. 

Abnormal indole derivatives in the urine and low levels of serotonin (a product of tryptophan metabolism) in blood and brain point to a defect in tryptophan metabolism in PKU. 5-Hydroxytryptophan decarboxylase, which catalyzes the conversion of 5-hydroxytryptophan to serotonin, is inhibited in vitro by some of the metabolites of phenylalanine. Phenylalanine hydroxylase is similar to the enzyme that catalyzes the hydroxylation of tryptophan to 5-hydroxytryptophan, a precursor of serotonin. In vitro, phenylalanine is also found to inhibit the hydroxylation of tryptophan. The mental defects associated with PKU may be caused by decreased production of serotonin. High phenylalanine levels may disturb the transport of amino... 

The majority of catecholamine and serotonin biosynthesis occurs within the nerve terminals by synthetic enzymes transported from the neuronal cell bodies. In all catecholamine neurons, the rate-limiting step in synthesis is conversion of tyrosine to dihydroxyphenylalanine by tyrosine hydroxylase. Dihydroxyphenylalanine is then converted to DA, norepinephrine, and epinephrine through a sequential process involving L-aromatic amino acid decarboxylase (conversion of dihydroxyphenylalanine to DA), dopamine-P-hydroxylase (conversion of DA to norepinephrine), and phenylethanol-amine-N-methyltransferase (conversion of norepinephrine to epinephrine). Cell-specific expression of these enzymes determines the main neurotransmitter for an individual catecholamine neuron. The synthesis pathway for serotonin involves a two-step process in which tryptophan hydroxylase first converts tryptophan to 5-hydroxytryptophan, which is then converted to... 

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