Tryptophan decarboxylase hydroxylase

Fig. 3. Biosynthesis of TIAs in C. roseus. Solid arrows indicate single enzymatic conversions, whereas dashed arrows indicate multiple enzymatic conversions. AS Anthranilate synthase, DXS D-l-deoxyxylulose 5-phosphate synthase G10H geraniol 10-hydroxylase CPR cytochrome P450 reductase TDC tryptophan decarboxylase STR strictosidine synthase SGD strictosidine /1-D-glucosidase D4H desacetoxyvindoline 4-hydroxylase DAT acetyl-CoA 4-O-deacetylvindoline 4-O-acetyl transferase. Genes regulated by ORCA3 are underlined. Reprinted with permission from [91]. Copyright (2000) American Association for the Advancement of Science...

Fig. 8.1 Sequence of reactions and pathways involved in the biosynthesis of indole alkaloids in Catharanthus roseus. The dotted lines indicate multiple and/or uncharacterized enzyme steps. Tryptophan decarboxylase (TDC), Geraniol Hydroxylase (GH), Deoxyloganin synthase (DS), Secologanin Synthase (SLS) Strictosidine synthase (STR1), Strictosidine glucosidase (SG), Tabersonine-16-hydroxylase (T16H), Tabersonine 6,7-eposidase (T6,7E), Desacetoxyvindoline-4-hydroxylase (D4H), Deacetyl-vindoline-4-O-acetyltransferase (DAT) and Minovincinine-19-O-acetyltransferase (MAT) represent some of the enzyme steps that have been characterized.

Tryptophan hydroxylase uses 02 and the electron donor BH4 to hydroxylate C-5 of tryptophan. The product, called 5-hyroxy-tryptophan, then undergoes a decarboxylation catalyzed by 5-hydroxy tryptophan decarboxylase, a pyridoxal phosphate-requiring enzyme. Serotonin, often referred to as 5-hydroxytryptamine, is the product of this reacdon. 

I Tryptophan 5-hydroxylase 5-Hydroxy tryptophan I Aromatic L-amino acid decarboxylase 5-Hydroxytryptamine (serotonin)... 

Fig. (3). Compartmentalization of the biosynthetic pathway of terpenoid indole alkaloids in plant cells. G10H geraniol 16-hydroxylase SLS secologanin synthase TDC tryptophan decarboxylase STR strictosidine synthase SGD strictosidine P-D-glucosidade T16H tabersonine 16-hydroxylase OMT S-adenosyl - L-methionine 16-hydroxytabereonine - 16-O-methyltransferase NMT S-adenosyl - /.-methionine 16-methoxy - 2,3-dihydro-3-hydroxytabersonine - A -methyltransferase D4H desacetoxy vindoline 4-hydroxylase DAT acetylcoenzyme A 4-O-deacetylvindoline 4-O-aeetyltransferase PRX peroxidase.

Fig. (4). Early steps of the biosynthesis of terpenoid indole alkaloids in Catharanthus roseus. Triple arrowheads indicate multiple steps. G10H geraniol 16-hydroxylase TDC tryptophan decarboxylase STR strictosidine synthase.

The most importaiit enzymes on this model are TDC (tryptophan decarboxylase), GlOH (geraniol 10-hydroxylase) and SS (strictoside symthase). NADPH, PO (peroxidase), O (oxidase), and NADlf are all active in different Catharantus alkaloid formations. The biochemical models are subject to both qualitative and quantitative alkaloid analysis. Not all enzymes par-tieipating in alkaloid symthesis and degradation are yet known. Alkaloid enzymatology is, therefore, a growing research area. 

Park S, Kang K, Lee SW, Ahn MJ, Bae JM, Back K (2011) Production of serotonin by dual expression of tryptophan decarboxylase and tryptamine 5-hydroxylase in Escherichia coli. Appl Microbiol Biotechnol 89 1387-1394... 

Fig. 8.5 Compartmentation of alkaloid biosynthesis in Cathamnthus roseus. AS anthianilate synthase, CR NADPH cathenamine reductase, DAT deacetylvindoline 17-O-acetyltransferase, ER endoplasmic reticulum, GlOH geraniol 10-hydroxylase, GAP glyceraldehyde-3-phosphate, NMT S-adenosyl-L-methionine methoxy-2, 16-dihydro-16-hydioxylagersonine-lV-methyltransferase, OHT desacetoxyvindoline-4-hydroxylase, SGD strictosidine -glucosidase, STR strictosidine synthase TDC tryptophan decarboxylase, THAS NADPH tetrahydroalstonine reductase (Adopted from Ref. [10])... 

Fig. 8.7 Biosynthetic pathway for monoteipenoid indole alkaloid (MIA) biosynthesis in plants. TDC tryptophan decarboxylase, STR strictosidine synthase, SGD strictosidine -o-glucosidase, T16H tabersonine 16-hydroxylase, D4H desacetoxyvindolme 4-hydroxylase, DAT deacetylvindoline 4-O-acetyltransferase (Adopted from Ref. [3])...

L-aromatic amino add decarboxylase (EC 4.1.1.26) is a stereospedfic enzyme for several l-aromatic amino acids (phenylalanine, tyrosine, DOPA. S-HTP). It is widely distributed and is characterized by its pyridoxal-S -phosphate requirement as coenzyme. The general r61e of this enzyme in the biogenesis of many amines is well documented but its regulatory action seems doubtful in view of its large excess compared with the low levels of tryptophan-S-hydroxylase and tyrosine hydroxylase. Numerous substances belonging to various chemical classes inhibit this enzyme in vivo and have been reviewed in Section B. Chapter 5.2 and elsewhere... 

Figure 4.9 Biosynthesis of monoterpenoid indole alkaloids. Enzyme abbreviations TDC, tryptophan decarboxylase STR, strictosidine synthase SGD, strictosidine f-d-glucosidase T16H, tabersonine 16-hydroxylase D4H, desacetoxyvindoline 4-hydroxylase DAT, deacetylvindoline 4-O-acetyltransferase.

TH = Tyrosine hydroxylase TPH = Tryptophan 5 - hydroxylase DC = Dopa decarboxylase DH = Dopamine 3-hydroxyIase... 

In the case of hyperphenylalaninaemia, which occurs ia phenylketonuria because of a congenital absence of phenylalanine hydroxylase, the observed phenylalanine inhibition of proteia synthesis may result from competition between T.-phenylalanine and L-methionine for methionyl-/RNA. Patients sufferiag from maple symp urine disease, an inborn lack of branched chain oxo acid decarboxylase, are mentally retarded unless the condition is treated early enough. It is possible that the high level of branched-chain amino acids inhibits uptake of L-tryptophan and L-tyrosiae iato the brain. Brain iajury of mice within ten days after thek bkth was reported as a result of hypodermic kijections of monosodium glutamate (MSG) (0.5—4 g/kg). However, the FDA concluded that MSG is a safe kigredient, because mice are bom with underdeveloped brains regardless of MSG kijections (106). 

Figure 13.7 Synthesis and structure of the trace amines phenylethylamine, /)-tyramine and tryptamine. These are all formed by decarboxylation rather than hydroxylation of the precursors of the established monoamine neurotransmitters, dopamine and 5-HT. (1) Decarboxylation by aromatic L-amino acid decarboxylase (2) phenylaline hydroxylase (3) tyrosine hydroxylase (4) tryptophan hydroxylase...

Hotchkiss, A.J. Morgan, M.E. and Gibb, J.W. The long-term effects of multiple doses of methamphetamine on neostriatal tryptophan hydroxylase, tyrosine hydroxylase, choline acetyltransferase and glutamate decarboxylase activities. Life Sci 25 1373-1378. 1979. 

Figure 1. Biosynthetic pathways for biogenic amines. In Drosophila and vertebrates decarboxylation of DOPA and 5-hydroxy-tryptophan is catalyzed by the same enzyme, DDC. In vertebrates this enzyme is called amino acid decarboxylase (AADC). Only vertebrates further metabolize dopamine to norepinephrine and epinephrine. TH, tryosine hydroxylase DDC, DOPA decarboxylase DBH, dopamine b-hydroxylase PNMT, phenylethanolamine N-methyltransferase. Tryp-OH tryptophan hydroxylase.

Serotonin is an indolamine neurotransmitter, derived from the amino acid L-tryptophan. Tryptophan is converted to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase. 5-HTP is converted to 5-hydroxytryptamine (serotonin, 5-HT) by aromatic amino acid decarboxylase. In the pineal gland, 5-HT may be further converted to /V-acetyl serotonin by 5-HT /V-acetyltransferase and then to melatonin by 5-hyroxyindole-O-methyltransferase. 5-HT is catabolized by monoamine oxidase, and the primary end metabolite is 5-hydroxyindoleacetic acid (5-HIAA). 

Following the synthesis of 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase, the enzyme aromatic amino acid decarboxylase (also known as 5-HTP or dopa decarboxylase) then decarboxylates the amino acid to 5-HT. L-Aromatic amino acid decarboxylase is approximately 60% bound in the nerve terminal and requires pyridoxal phosphate as an essential enzyme. 

It is an indole ethylamine formed in biological systems from the amino acid L-tryptophan by hydroxylation with tryptophan hydroxylase enzyme, followed by the decarboxylation by the nonspecific aromatic L-amino acid decarboxylase. 5-HT is then taken up into secretory granules and stored. 

Whilst the term biogenic amine strictly encompasses all amines of biological origin, for the purpose of this article it will be employed to refer to the catecholamine (dopamine, noradrenaline) and serotonin group of neurotransmitters. These neurotransmitters are generated from the amino acid precursors tyrosine and tryptophan, respectively, via the action of the tetrahydrobiopterin (BH4)-dependent tyrosine and tryptophan hydroxylases. Hydroxylation of the amino acid substrates leads to formation of 3,4-dihydroxy-l-phenylalanine ( -dopa) and 5-hydroxytryptophan, which are then decarboxylated via the pyridoxalphosphate-dependent aromatic amino acid decarboxylase (AADC) to yield dopamine and serotonin [4]. In noradrenergic neurones, dopamine is further metabolised to noradrenaline through the action of dopamine-jS-hydroxylase [1]. 

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. 

One of the best characterized physiological functions of (6R)-tetrahydrobio-pterin (BH4, 43) is the action as a cofactor for aromatic amino acid hydroxylases (Scheme 28). There are three types of aromatic amino acid hydroxylases phenylalanine hydroxylase [PAH phenylalanine monooxygenase (EC 1.14.16.1)], tyrosine hydroxylase [TH tyrosine monooxygenase (EC 1.14.16.2)] and tryptophan hydroxylase [TPH tryptophan monooxygenase (EC 1.14.16.4)]. PAH converts L-phenylalanine (125) to L-tyrosine (126), a reaction important for the catabolism of excess phenylalanine taken from the diet. TH and TPH catalyze the first step in the biosyntheses of catecholamines and serotonin, respectively. Catecholamines, i.e., dopamine, noradrenaline and adrenaline, and serotonin, are important neurotransmitters and hormones. TH hydroxylates L-tyrosine (126) to form l-DOPA (3,4-dihydroxyphenylalanine, 127), and TPH catalyzes the hydroxylation of L-tryptophan (128) to 5-hydroxytryptophan (129). The hydroxylated products, 127 and 129, are decarboxylated by the action of aromatic amino acid decarboxylase to dopamine (130) and serotonin (131), respectively. 

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