Tryptophan oxidase

Two genes appear to be essential for indolocarbazole production in actinomycetes. One of the genes encodes a tryptophan oxidase (rebO, staO), while the second one codes for a heme-containing oxidase (rebD, staD). In their absence, no bisindole intermediates can be formed [23,33]. 

Two enzyme systems have been discovered that initiate the catabolism of tryptophan and lead to the products shown in Fig. 13. These are tryptophan oxidase-peroxidase and kynureninase. Their roles in the catabolic process will be discussed below. 

The dioxygenases, which incorporate two atoms of oxygen into one molecule of the substrate, are enzymes which are frequently involved in the cleavage of bonds in an aromatic ring. Typical of these are homogentisate oxidase and L-tryptophan oxidase (L-tryptophan pyrrolase) and two bacterial oxygenases pyrocatechase and metapyrocatechase. ... 

Formation of kynurenine from tryptophan was discovered in liver extracts by Kotake and Masayama 289). These authors proposed the name tryptophan pyrrolase for the enzyme. Knox and Mehler 290) subsequently showed that the formation of kynurenine consisted of two enzyme reactions, an initial oxidation to formylkynurenine followed by hydrolysis to kynurenine. Because the reaction was stimulated by HsO produced in situ it was assumed that there was an intermediate formation and utilization of peroxide in the oxidation. For this reason the enzyme was renamed tryptophan oxidase-peroxidase by Knox. Experiments with O showed that molecular O2 was incorporated into the reaction products 291). One mole of O2 per mole of tryptophan was contained in the formylkynurenine. When H20 was tested, very little 0 was utilized. This observation led Tanaka and Knox 292) to return to the use of the original name, tryptophan pyrrolase. 

In addition to activities ordinarily ascribed to them, peroxidase and catalase possess properties as oxygen transferases and mixed function oxidases. They may exist in functionally active ferrous forms which have, like hemc lobin and myoglobin, the property of combining with molecular oxygen. This oxygen may be transferred to substrate, or be reduced in steps. For purposes of the present review, mechanisms that have been proposed for peroxidatic and catalatic oxidations will be summarized and followed by discussion of dihydroxyfumaric acid oxidase, tryptophan oxidase, and indolyl-acetic oxidase and related oxidases, and indole oxidase. All of these have properties in common with peroxidase and catalase. 

There a number of cases other than those of dihydroxyfumaric acid oxidase and tryptophan oxidase in which peroxidases appear to play the part of oxidases. These include indolylacetic acid oxidase and the related indolylpropionic and indolylbutyric acid oxidases (285, 415,416,618,733,777), the oxidase of oxalic, oxalacetic, ketomalonic, and dihydroxytartaric acids (414), of phenylacetaldehyde (413) and saturated fatty acid oxidase (711). 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

Examples include the liver enzymes, homogentisate dioxygenase (oxidase) and 3-hydroxyantliranilate dioxygenase (oxidase), that contain iron and L-trypto-phan dioxygenase (tryptophan pyrrolase) (Chapter 30), that utilizes heme. 

Figure 9.4 The synthesis and metabolism of 5-HT. The primary substrate for the pathway is the essential amino acid, tryptophan and its hydroxylation to 5-hydrox5dryptophan is the rate-limiting step in the synthesis of 5-HT. The cytoplasmic enzyme, monoamine oxidase (MAOa), is ultimately responsible for the catabolism of 5-HT to 5-hydroxyindoleacetic acid...

The product of the hydroxylation of tryptophan, 5-hydroxytryptophan, is rapidly decarboxylated to 5-HT by a specific decarboxylase enzyme. This is generally thought to be a soluble enzyme which suggests that 5-HT is synthesised in the cytoplasm, before it is taken up into the storage vesicles. If this is the case, then considerable losses might be incurred from its metabolism by monoamine oxidase before it reaches the storage vesicles. Indeed, this could explain why 5-HT turnover seems to greatly exceed its rate of release. 

Grahame-Smith, DG (1971) Studies in vivo on the relationship between brain tryptophan, brain 5HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. J. Neurochem. 18 1053-1066. 

Narumiya S, K Takai, T Tokuyama, Y Noda, H Ushiro, O Hayaishi (1979) A new metabolic pathway of tryptophan initiated by tryptophan side chain oxidase. J Biol Chem 254 7007-7015. 

Figure 1. Schematic outline of various products and associated enzymes from the shikimate and phenolic pathways in plants (and some microorganisms). Enzymes (1) 3-deoxy-2-oxo-D-arabino-heptulosate-7-phosphate synthase (2) 5-dehydroquinate synthase (3) shikimate dehydrogenase (4) shikimate kinase (5) 5-enol-pyruvylshikimate-3-phosphate synthase (6) chorismate synthase (7) chorismate mutase (8) prephenate dehydrogenase (9) tyrosine aminotransferase (10) prephenate dehydratase (11) phenylalanine aminotransferase (12) anthranilate synthase (13) tryptophan synthase (14) phenylalanine ammonia-lyase (15) tyrosine ammonia-lyase and (16) polyphenol oxidase. (From ACS Symposium Series No. 181, 1982) (62).

Yoshida, K. et al. (2002). Monoamine oxidase a gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26, 1279-83. 

LUDWIG-MULLER, J., HILGENBERG, W., A plasma membrane-bound enzyme oxidases L-tryptophan to indole-3-acetaldoxime, Physiol. Plant., 1988, 74, 240-250. 

In one series of experiments the cytochrome c oxidase mutations replaced acidic residues by neutral ones, and some of them were thus expected to alter the nature of binding of the protein to cytochrome c. From the pattern of dependence of the heme c to Cua electron-transfer rate constant on these mutations it was deduced that the binding of cytochrome c to cytochrome c oxidase is mediated by electrostatic interactions between four specific acidic residues on cytochrome c oxidase and lysines on cytochrome c. In another series of experiments, tryptophan 143 of cytochrome c oxidase was mutated to Phe or Ala. These mutations had an insignificant effect on the binding of the two proteins, but they dramatically reduced the rate constant for electron transfer from heme c to Cua- It was concluded that electron transfer from... 

Fig. 1. Prosthetic groups in oxidases (A FAD B Thio-Tyrosine C NAD(P) + D 6-Hydroxy-DOPA E Methoxanthin (Pyrroloquinoline quinone PQQ) F Tryptophane-Tryptophan quinone)...

In the resonance Raman spectra of GO0X (125), vibrational modes have been assigned to both the tyrosinate ligand (Tyr 495) as well as the tyrosyl radical (Tyr 272). The spectrum does not provide evidence for the speculation that the tyrosyl radical is delocalized onto the jr-stacked tryptophan residue (Trp 290) (126, 127). Recent results of high-frequency EPR measurement (30) on the apogalactose oxidase radical are also consistent with the radical spin density being localized on the modified Tyr 272 moiety only. 

L-Amino acid oxidase has been used to measure L-phenylalanine and involves the addition of a sodium arsenate-borate buffer, which promotes the conversion of the oxidation product, phenylpyruvic acid, to its enol form, which then forms a borate complex having an absorption maximum at 308 nm. Tyrosine and tryptophan react similarly but their enol-borate complexes have different absorption maxima at 330 and 350 nm respectively. Thus by taking absorbance readings at these wavelengths the specificity of the assay is improved. The assay for L-alanine may also be made almost completely specific by converting the L-pyruvate formed in the oxidation reaction to L-lactate by the addition of lactate dehydrogenase (EC 1.1.1.27) and monitoring the oxidation of NADH at 340 nm. 

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). 

Figure 2.18. The major pathway leading to the synthesis and metabolism of 5-hydroxytryptamine (5-HT). Metabolism of tryptophan to tryptamine is a minor pathway which may be of functional importance following administration of a monoamine oxidase (MAO) inhibitor. Tryptamine is a trace amine. L-Aromatic amino acid decarboxylase is also known to decarboxylate dopa and therefore the term "L-aromatic amino acid decarboxylase" refers to both "dopa decarboxylase"...

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