Tryptophan oxidation effects

The content of the tryptophan-oxidizing enzyme system present in liver commonly is low. It can be increased as much as tenfold through the prior feeding of tryptophan by a mechanism resembling that of enzyme adaptation observed in microorganisms. A much smaller response (twofold) is obtained with certain other substances not substrates of the enzyme system, e.g., epinephrine and histamine. This latter group of compounds has no effect in adrenalectomized animals, and thus, it appears, the increase is caused through a stimulation by the pituitary-adrenal system. ... 

The implication of hydrogen peroxide as a component of the tryptophan-oxidizing system came from experiments in which increased kynurenine formation was found in samples supplemented with materials that caused increased H2O2 production. Lower activity was found when extra catalase was added, but maximum activity appeared when the peroxide-generating system and catalase were balanced an excess of either caused decreased activity. Recently, Tanaka and Knox (1959) have shown that the effect of hydrogen peroxide is restricted to an initial activation of the enzyme, and that, subsequently, neither peroxide formation nor catalase influences the course of the reaction. Free hydrogen peroxide, therefore, appears eliminated as a product or reagent in the oxidation of tryptophan. 

The effect of ionizing radiation (x or y rays) on tryptophan or on tryptophan-containing proteins in aerated aqueous solution is seemingly to bring about partial conversion of tryptophan to formylkynurenine (5, 206, 300). The oxidizing species are presumed to be hydroxy and hydroperoxy radicals. Oxindolylalanine does not seem to be an intermediate in the reaction. Suggested mechanisms (206, 300) propose 2-hydroxy-3-hydroperoxyindoline (86) as an intermediate. However, in the light of recent theories on tryptophan oxidation, which were discussed in other sections a modification of the above discussed mechanism can be also proposed which involves hydroperoxyindolenine as an intermediate. 

Samy, T. S. a., M. Atrey, H. Maeda, and J. Meienhofer Selective Tryptophan Oxidation in the Antitumor Protein Neocarzinostatin and Effects on Conformational and Biological Activity. Biochemistry 13, 1007-1014 (1974). 

Chapters 9, 10 and 11 describe methods for substitution directly on the ring with successive attention to Nl, C2 and C3. Chapters 12 and 13 are devoted to substituent modification as C3. Chapter 12 is a general discussion of these methods, while Chapter 13 covers the important special cases of the synthesis of 2-aminoethyl (tryptaminc) and 2-aminopropanoic acid (tryptophan) side-chains. Chapter 14 deals with methods for effecting carbo cyclic substitution. Chapter 15 describes synthetically important oxidation and reduction reactions which are characteristic of indoles. Chapter 16 illustrates methods for elaboration of indoles via cycloaddition reactions. 

Graham, D.G. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14 633-643. 1978. Hotchkiss, A.J., and Gibb, J.W. Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. J Pharmacol Exp Ther 214 257-262, 1980. 

Investigations of the effects of UV- and hypochlorite-induced oxidative modification of 20 amino acids and human serum albumin (HSA) on their antiradical properties showed unexpected results [36], Seven amino acids (cystine, histidine, methionine, phenylalanine, serine, tryptophan, and tyrosine) and HSA developed ACW following oxidation (see examples in Fig. 14). The fresh (produced in 1998) HSA from Serva had no antiradical capacity, but it acquired this quality during irradiation. The out-of-date HSA sample (Dessau, GDR, 1987, expiration date 7/1/1992) showed a remarkable ACW even in an unirradiated state. 

Domanski, T. L., He, Y. A., Khan, K. K., Roussel, F., Wang, Q., and Halpert, J. R. (2001) Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition site residues and effect on substrate oxidation and coop-erativity. Biochemistry 40, 10,150-10,160. 

Although the oxidation of indoles by air and light has been studied extensively, e.g., the photooxidation of tryptophan to kynurenine and 3-hydroxykynurenine in the presence of methylene blue as sensitizer,311 313 little is known about the course of pyrrole photooxidation.173180 184 Under very mild conditions, irradiation of 2,3,4,5-tetra-phenylpyrrole in methanol and in the presence of air and methylene blue effected its oxidation to 5-methoxy-3,4-epoxy-2,3,4,5-tetraphenyl-A -pyrroline (CXVI) and a-A-benzoylamino-a -benzoyl stilbene(CXVII).303 Photooxidation in the presence of potassium hydroxide gave the lactam (CXVIII). 

A kinetic study of the photosensitized oxidation of tryptophan-alkyl esters in Triton X-100 micellar solutions has been carried out by Criado et al. [24], The results obtained are presented in Table 6. These data show an important decrease in the relevance of the photo-oxidative pathway in the esterified compounds in the presence of the micelles. The magnitude of the effect seems to be extremely sensitive to the location of the probe, increasing as the length of the ester hydrocarbon chain increases. These results are interpreted in terms of the competition between the local oxygen concentration and the solvent micropolarity effect that... 

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