5HTP

HTP precursor, 5HTP (effect preventable by 5HT1A Reversed withdrawal-induced immobility in forced swim test Mannucci et al. (2006)... 

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. 

Fig. 6.12. Chromatography of 3H-labelled extracted products following incubation of homogenates of Hymenolepis diminuta in [3H]tryptophan 5HT, 5-hydroxytryptamine 5HTP, 5-hydroxytryptophan TRY, tryptophan or, origin fr, solvent front. The data were obtained by subtracting the radioactivity in boiled homogenates (blanks) from that in unboiled homogenates. Radiolabelled tryptophan was metabolised in the latter to [3H]5HTP and [3H]5HT. (After Ribeiro Webb, 1983a.)...

Indoleamine stock solutions 0.1 mg/mL in antioxidant mixture see Section 2 1, Item 8). Prepare separate stock solutions of 5HT, 5HTP, DOPAC, and 5HIAA by dissolving 5 mg of each in 50 mL of filtered antioxidant mixture Stored at 4" C in brown bottles or bottles covered with aluminum foil, the solutions are stable for 2 mo... 

In the hippocampus, a 3-mm probe is placed and dialyzed at a flow rate of 1 pL/min with Ringer s solution containing 2.2 toM Ca (see Note 3) and samples are taken every 20 min. Samples are collected into vials containing the appropriate volume of antioxidant solution (see Note 4). Typical baseline values under these conditions are for 5HT, 29.5 5.1 finol/20 min (mean SEM, n = 35) and for 5HIAA, 7.0 0.7 pmol/20 min (mean SEM, n = 36). The limits of detection for 5HT, 5HTP, DOPAC, and 5HIAA are 0.5,0.4,0.5, and 0.7 finol mjected, respectively. 

Fig. 2.1. Metabolism of serotonin and the catecholamines. 2.1 = tyrosine hydroxylase 2.2 = aromatic L-amino acid decarboxylase 2.3 = dopamine -hydroxylase 2.4 = monoamine oxidase. VLA = vanillactic acid 30MD = 3-0-methyldopa 5HTP = 5-hydroxytryp-tophan 5HIAA = 5-hydroxyindoleacetic acid DOPAC = dihydroxyphenylacetic acid HVA = homovanillic acid VMA = vanillylmandelic acid MHPG = 3-methoxy-4-hydroxy-...

MD, 3-0-methyldopa 5HTP, 5-hydroxytryptophan HVA, homovanillic acid 5HIAA, 5-hydroxyindoleacetic acid. 

MD, 3-0-methyldopa 5HTP, 5-hydroxytryptophan NE, norepinephrine E, epinephrine DA, dopamine NMN, nor-metanephrine 3MT, 3-methoxytyramine VMA, vanillylmandelic acid 5HT, serotonin HVA, homovanillic acid 5HIAA, 5-hydroxyindoleacetic acid VIA, vanillactic acid. 

Condi- 30MD L-Dopa 5HTP 5HIAA HVA MHPG DO- NE E DA NMN 3MT VMA 5HT VLA... 

The conversion of tr3rptophan to serotonin requires both decarboxylation and hydroxylation of the aromatic ring. Two routes are, therefore, conceivable (1) Hydroxylation to 3rield 5-hydroxy tryptophan (5HTP), followed by decarboxylation, or, (2) decarboxylation to yield tryptamine, followed by hydroxylation at the 5-position. 

When large amounts of tryptamine were administered to animals, the serotonin contents of tissues were not increa.sed. Administration of potent inhibitors of monoamine oxidase (MAO) along with tryptamine to prevent its destruction was also without effect. Tryptamine administration did not result in an increased excretion of the serotonin metabolite, 5HIAA. On the other hand, administration of comparable amounts of either tryptophan or 5HTP does increase tissue levels of serotonin and urinary excretion of 5HIAA... 

The following abbreviations are used 5HTP, 5-hydroxytryptophan 5HIAA, 5-hydroxyindoleacetic acid MAO, monoamine oxidase DPN, diphosphopyridine nucleotide ATP, adeno.sine triphosphate Dopa, 3,4-dihydroxyphenylalanine. 

The first evidence for 5HTP as an intermediate in serotonin formation was the demonstration of potent 5HTP decarboxylase activity in tissues. This enzyme was purified from guinea pig and hog kidney and shown to be separable from 3,4-dihydroxyphenylalanine(dopa) decarboxylase. By procedures involving differential heat inactivation, salt fractionation, and adsorption on alumina it was possible to change the ratio of dopa decarboxylase to 5HTP decarboxylase by as much as twentyfold (Clark el al., 1954). 

HTP is not (Clark et al., 1954). Other factors which argue for two separate enzymes are (1) tremendously different pH optima, 6.9 for dopa and 8.1 for 5HTP (2) tremendously different substrate enzyme affinities and (3) marked differences in their abilities to dissociate from the coenzyme, pyri-doxal phosphate. 

In addition to pyridoxal phosphate it has been reported that 5HTP decarboxylase also seems to require a metal. This metal requirement stems from the finding that chelating agents such as ethylenediamine tetraacetate inhibit activity (Beiler and Martin, 1954). Inhibition by chelating agents has been confirmed in the reviewer s laboratory. 

Inhibition of 5HTP decarboxylase has been suggested as the mechanism of action of one-hydrazinophthalazine (Perry et al., 1955 von Schuler and Meier, 1955), a potent hypotensive agent. However, no supporting evidence is given for this action in the article. Studies in the author s laboratory have corroborated this report and indicate that 1-hydrazinophthalazine can... 

HTP decarboxylase has been found in all tissues which contain serotonin. In the central nervous system the localization of 5HTP decarboxylase parallels the localization of serotonin (Gaddum and Giarman, 1956 Bogdanski et al., 1957). Tissues, such as cerebellum, which contain little serotonin contain but traces of 5HTP decarboxylase, whereas hypothalamus is rich in both. From these and other considerations it would appear that serotonin is made centrally. 

It has also been possible to show marked diminution in the serotonin depots of chicks which were raised from hatching on a vitamin Be-defi-cient diet (Weissbach et al., 1957a). As shown in Table I the amount of serotonin in all tissues was markedly diminished. When 5HTP was adminis-... 

A, adrenaline COMT, catechol-O-methyl transferase CSF, cerebrospinal fluid DA, 3,4-dihydroxyphenylethylamine (dopamine) Dopa, 3,4-dihydroxyphenylalanine 5HIAA, 5-hydroxyindoleacetic acid 5HT, 5-hydroxytryptamine (serotonin) 5HTP, 5-hydroxytryptophan HVA, 3-methoxy-4-hydroxyphenylacetic acid (homovanillic acid) MAO, monoamine oxidase MAOI, monoamine oxidase inhibitor MHPG,... 

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