5-hydroxytryptophan decarboxylase

Aromatic L-amino acid decarboxylase catalyzes the decarboxylation of l-5-hydroxytryptophan (l-5-HTP) to serotonin (5-HT). In the assay, l-5-HTP was used as the substrate and the formation of 5-HT was measured. 

The enzyme was prepared from rat and human cerebral cortex. Cortical samples were homogenized in a sucrose solution, and the homogenate was used directly as the enzyme source. 

3 Dope Decarboxylase(L-Aromatlc Amino Acid Decarboxylase) (Nagatsu et al., 1979 D Erme et al., 1980) 

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Bogdanski, D.F. Weissbach, H. and Udenfriend, S. The distribution of serotonin, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in brain. J Neurochem 1 272-278, 1957. 

Histamine is synthesized from the amino acid histidine by simple decarboxylation catalysed by histidine decarboxylase. Serotonin is synthesized primarily in platelets, the gastro-intestinal (GI) tract and the brain from the indolyl amino acid tryptophan tryptophan —> 5-hydroxytryptophan [via tryptophan hydroxylase + tetrahydrobiopterin] —> 5-hydroxy-tryptamine (serotonin) [via 5-hydroxytryptophan decarboxylase]. 

In the presence of the cofactor pyridoxyl phosphate, Dopa decarboxylase catalyzes the decarboxylation of L-dopa to dopamine. This enzyme has been shown to be the same protein as 5-hydroxytryptophan decarboxylase, and both are referred to by the name aromatic L-amino acid decarboxylase (AADC). 

Figure 8.4. Pathways of tryptophan metaholism. Tryptophan dioxygenase, EC 1.13.11.11 formylkynurenine formamidase, EC 3.5.1.9 kynurenine hydroxylase, EC 1.14.13.9 kynureninase, EC 3.7.1.3 3-hydroxyanthranilate oxidase, EC 1.10.3.5 picolinate carboxylase, EC 4.1.1.45 kynurenine oxoglutarate aminotransferase, EC 2.6.1.7 kynurenine glyoxylate aminotransferase, 2.6.1.63 tryptophan hydroxylase, EC 1.14.16.4 and 5-hydroxytryptophan decarboxylase, EC 4.1.1.26. Relative molecular masses (Mr) tryptophan, 204.2 serotonin, 176.2 kynurenine, 208.2 3-hydroxykynurenine, 223.2 kynurenic acid, 189.2 xanthurenic acid, 205.2 and quinolinic acid 167.1. CoA, coenzyme A.

Pyridoxine plays a role in (1) the control of the hypothalamo-pituitary end-organ system, (2) melatonin synthesis, and (3) convulsive seizure activity. Neurological deficits resulting from pyridoxine deficiency can largely be explained by decreased activity of glutamic acid decarboxylase, 5-hydroxytryptophan decarboxylase, and ornithine decarboxylase (Dakshinamurti et al., 1990). The products of these... 

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... 

McCaman, R. E., Rodriguez de Lores Arnaiz, G. and De Robertis, E. (1965) Species differences in subcellular distribution of choline acetylase in the CNS. A study of choline acetylase, acetylcholinesterase, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in four species. J. Neurochem., 12, 927-935. 

By increasing the activity of the kynurenine pathway, estrogens could also increase the requirements for PLP and make less available to act as the coenzyme for 5-hydroxytryptophan decarboxylase, or estrogen conjugates could displace PLP from the decarboxylase coenzyme directly. Even though in nonhuman mammals tryptophan hydroxylase, not the decarboxylase, is thought to be rate-limiting in serotonin synthesis (Jl), levels of decarboxylase are said to be so low in human brain... 

Acetylcholine is formed from choline (which is also an important constituent of phospholipids) and acetyl CoA under the catalytic influence of choline acetyl-ase. It is hydrolised by acetylcholinesterase or choline esterase. Two important steps in the formation of noradrenaline from tyr dopa decarboxylase and dopamine hydroxylase. Adrenaline is formed from noradrenaline by phenyl ethanolamine A -methyltransferase. Both noradrenaline and adrenaline are metabolised by catechol 0-methyl transferase or monoamine oxidase. Some later steps in their metabolism involve aldehyde dehydrogenase and alcohol dehydrogenase (aldehyde reductase), After hydroxylation to its 5-hydroxy derivative, tryptophan is converted by 5-hydroxytryptophan decarboxylase to 5-hydroxytryptamine (serotonin). The major routes of serotonin metabolism involve either monoamine oxidase or hydroxyindole 0-methyltransferase. Histamine is synthesised from histidine by histidine decarboxylase, and is metabolised by either diamine oxidase or histamine Af-methyltransferase. Gamma aminobutyric acid is formed by glutamate decarboxylase and metabolised by... 

Hydroxytryptophan decarboxylase Monoamine oxidase Hydroxylindole 0-methyltransferase... 

The presence of indol derivatives in the urine of phenylketonuric patients is more difficult to understand. The experiments of Tyler and Armstrong [79] suggest that there are side effects of the main metabolic block. By keeping the patient on a diet containing only sufficient amounts of phenylalanine to maintain normal growth and normal protein synthesis, these authors demonstrated that all these patients biochemical symptoms disappeared, including the excretion of indole derivatives. Furthermore, it was demonstrated that hydroxytryptophan decarboxylase (an enzyme identical to dopa decarboxylase) is inhibited by the abnormal metabolites in a way analogous to that for dopa decarboxylase. This may explain both the low levels of phenyltryptamine in patients with phenylketonuria and the accumulation of unidentified indole compounds [80, 81]. 

Both the absence of phenylalanine hydroxylase and the block of the 5-hydroxytryptophan decarboxylase could account for the low plasma and brain serotonin observed in patients with phenylketonuria. 

Dopa- and 5-hydroxytryptophane decarboxylase are probably identical. Both enzymes are similarly distributed in practically all tissues which have been examined, and the ratio of activity using dopa or 5-... 

Rosengren, E., Are dihydroxyphenylalanine decarboxylase and 5-hydroxytryptophan decarboxylase individual enzymes , Acta, physiol, scand. 49, 364 (1960). 

Yuwiller, a., Geller, E. and Eiduson, S., Studies on 5-hydroxytryptophan decarboxylase. I. In vitro inhibition and substrate interaction. Arch. Biochem. Biophys. 80, 162 (1959). 

Smith, S. E., The pharmacological actions of 3,4-dihydroxyphenyl-a-methylalanine (a-methyldopa), and inhibitor of 5-hydroxytryptophan decarboxylase, Brit. J. Pharmacol. 15, 319 (1960). 

Davison, A. N. and Sandler, M., Inhibition of 5-hydroxytryptophan decarboxylase by phenylalanine metabolites. Nature 181, 186 (1958). 

Hydroxytryptophane 3, 6 5-Hydroxytryptophane decarboxylase 3 5-Hydroxytryptophol 17,48 3-Hydroxytyramine see Dopamine Hyperserotoninuria 102 Hypertension 11, 21, 108, 109 Hyperthyroidism 20, 111 Hypothyroidism 20... 

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