Tryptophan oxidation, inhibition

Bihel, S., Birlouez-Aragon, I. 1998. Inhibition of tryptophan oxidation in the presence of iron-vitamin C by bovine lactoferrin. Int. Dairy J. 8, 637-641. 

Tryptophan oxidation in liver has been found to be adaptive (36,43,44)-Administration of the amino acid to rabbits or rats results in an approximately tenfold increase in the amount of the tryptophan oxidizing system. This rise in enzyme occurs some 6 hr after the administration of a single dose of tryptophan, and then rapidly decreases. This increase appears to be due to true synthesis, since ethionine will inhibit the adaptive formation of the enzyme (46). It is of interest that the only step in the conversion of tryptophan to nicotinic acid which is adaptive is the oxidation to formyl-kynurenine (43),. This is in contrast to the finding in bacteria, where a number of the enzymes in the tryptophan oxidation sequence have been found to be adaptive (43). 

Estimation of the Binding Site. Tryptophan-108 shows a specific reaction with iodine, distinguishing it from other tryptophan residues of lysoz3mie. When try-108 is selectively oxidized by iodine, lysozyme completely loses its activity. Nevertheless, the lysozyme still shows the ability to form an enzyme-substrate complex with CM-chitin. This observation contributes to the conclusion that try-62 is an essential binding site for a complex formation (13). All ozonized lysozymes formed strong complexes with CM-chitin and could only be eluted by 0.2N HA (Fig. 6). This further confirms that two tryptophan residues (108 and 111) are indispensible for the hydrolytic action of lysozyme, and that inactivation by ozone cannot be attributed to inhibition of substrate binding capability. 

The Fe-EDTA complex catalysed the oxidation of tryptophan and the hydroxyla-tion of salicylate in the presence of a superoxide-generating system, A partial inhibition by diethylenetriaminepenta-acetate was observed for the latter reaction and in the ethylene production from 2-keto-4-thiomethylbutyrate... 

Three novel pteridine alkaloids bearing two pteridine units and a tryptophan core have been isolated from the sponge Clathria sp <02T4481>. Structural requirements for inhibition of neural nitric oxide synthase (NOS-I) and 3D-QSAR analysis of 4-oxo-pteridine-based and 4-amino-pteridine-based inhibitors have been reported <02JMC2923>. 

In independent studies, Aprison et al. (A7) found among tryptophan metabolites that 3-hydroxyanthranilic acid was capable of inhibiting the oxidation of N,N-dimethyl-p-phenylendiamine by purified ceruloplasmin and serum oxidase. 

A recent study has described the inhibition of tyrosine nitration but not oxidation by tryptophan and tryptamine, indicating that nitration of the indole ring proceeds more favourably than nitration of the phenoxyl ring [118]. Methionine oxidation can be elicited by peroxynitrite and proceeds via two-step single electron reduction reactions yielding methionine sulphoxide as described previously [119]. 

Interferons represent a class of proteins with various biological properties.338339 These include the ability to inhibit intracellular replication of viruses and certain parasites,340 the ability to inhibit replication of certain types of tumor cells in vitro, 41 and the ability to modulate immune responses in vitro and in vivo in a positive or negative manner.339 Of the interferons, interferon-y (IFN-y) is thought to be a more effective immunomodulary agent and a more effective inhibitor of division of certain tumor cells in vitro than other interferons.339 One mechanism of IFN-y-mediated growth inhibition is the stimulation of cellular oxidation of tryptophan by indoleamine 2,3-dioxygenase.342 343... 

Christen, S., Thomas, S. R., Gamer, B., and Stocker, R., Inhibition by interferon-gamma of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway, /. Clin. Invest., 93, 2149, 1994. 

Rebeccamycin is a natural product that inhibits DNA topoisomerase I and has been studied as a potential anticancer agent because of the importance of DNA topoisomerase I in cell growth and proliferation. Rebeccamycin analogues are being used in clinical trials for the treatment of neoplastic tumors,renal cell cancer, and leukemia, " rehO is one of the 11 genes in the rebeccamycin biosynthetic cluster. The protein product, RebO, is an L-amino acid oxidase that contains a noncovalently bound FAD. RebO catalyzes the oxidation of 7-chloro-L-tryptophan in an early step in rebeccamycin biosynthesis (Equation (4)). 

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