Aromatic amino acid decarboxylase serotonin synthesis

There is a great deal of evidence that deficiency of serotonin (5-hydroxytryptamine) is a factor in depressive illness, and many antidepressant drugs act to decrease its catabolism or enhance its interaction with receptors. A key enzyme involved in the synthesis of serotonin (and the catecholamines) is aromatic amino acid decarboxylase, which is pyridoxal phosphate-dependent. Therefore, it has been suggested that vitamin Be deficiency may result in reduced formation of the neurotransmitters and thus be a factor in the etiology of depression. Conversely, it has been suggested that supplements of vitamin Be may increase aromatic amino acid decarboxylase activity, and increase amine synthesis and have a mood-elevating or antidepressant effect. There is little evidence that vitamin Be deficiency affects the activity of aromatic amino acid decarboxylase. In patients with kidney failure, undergoing renal dialysis, the brain concentration of pyridoxal phosphate falls to about 50% of normal, with no effect on serotonin, catecholamines, or their metabolites (Perry etal., 1985). 

Central effects on blood pressure regulation as a result of decreased synthesis of brain GABA and serotonin (5-hydroxytryptamine). Glutamate decarboxylase activity in the nervous system is especially sensitive to vitamin Bg depletion, possibly as a result of mechanism-dependent inactivation by transamination. Although there is no evidence that aromatic amino acid decarboxylase activity is reduced in vitamin Bg deficiency, there is reduced formation of serotonin in the central nervous system. 

The synthesis of 5-HT from tryptophan in serotonergic neurons occurs in two steps. First, the enzyme tryptophan hydroxylase catalyzes the conversion of tryptophan to 5-hydroxytryptophan (5-HTP). Then, the enzyme aromatic amino acid decarboxylase catalyzes the conversion of 5-FlTP to serotonin. 

Figure 12-3. Synthesis and metabolism of serotonin. TH = tryptophane hydroxylase AAD = l-aromatic amino acid decarboxylase MAO = monoamine oxidase ADH = aldehyde dehydrogenase. (Broken arrow indicates possible aberrant pathway.)...

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... 

The synthesis of serotonin from tryptophan is carried out in two steps controlled by two enzymes tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC). The second enzyme, A ADC, is also known as DOPA carboxylase or 5-hydroxytryptophan carboxylase when it acts specifically in 5-HT synthesis. In the first step, the TPH adds a hydroxyl chemical group (OH) to tryptophan to make 5-hydroxytryptophan, Fig (1). In the second step, AADC removes the carboxyl group (-COOH) from 5-hydroxy tryptophan to make serotonin. Fig (2). 

Fig (2). Aromatic L-amino acid decarboxylase also known as tryptophan decarboxylase, catalyses the synthesis of 5-bydnoxyiriplaminc (serotonin) from 5-hydroxytryptophan. lire reaction consists of a decarboxylation activity that is found in many human tissue cells... 

SYNTHESIS, STORAGE, AND RELEASE OF CATECHOLAMINES Synthesis—The steps in the synthesis of DA, NE (known outside the U.S. as noradrenaline), and Epi (known as adrenahne) are shown in Eigure 6-A. Tyrosine is sequentially 3-hydroxylated and decarboxylated to form DA. DA is 3-hydroxylated to yield NE (the transmitter in postganglionic nerves of the sympathetic branch of the ANS), which is N-methylated in chromaffin tissue to give Epi. The enzymes involved are not completely specific consequently, other endogenous substances and some drugs are also substrates. 5-hydroxytryptamine (5-HT, serotonin) can be produced from 5-hydroxy-L-tryptophan by aromatic L-amino acid decarboxylase (AAD or dopa decarboxylase). AAD also converts dopa into DA, and methyldopa to a-methyl-DA, which is converted to a-methyl-NE by dopamine /3-hydroxylase (Dj3H Table 6-4). 

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