Tryptophan photooxidation

Walrant, R and Santus, R., N-formyl-kynurenine, a tryptophan photooxidation product, as a photodynamic sensitizer, Photochem. Photobiol., 411, 1974, 1974. 

Jori et al. indicate that the estimation of formylkynurenine can be made by acid hydrolysis to kynurenine followed by analysis with an amino acid analyzer, but it is not clear from the paper (272) which of the two methods were used to estimate the actual figures reported. In addition, Jori et al. have as yet given no evidence in support of their claim that formylkynurenine is the single end-product of tryptophan photooxidation, but merely quote (272) in a footnote unpublished experi-... 

Walrant, P., and R. Santus N-Formylkynurenine, a Tryptophan Photooxidation Product, as a Photodinamic Sensitizer. Photochem. Photobiol. 19, 411-417 (1974). 

Finally superoxide radicals can also be generated photochemically in chloroplasts in the presence of ascorbate or of paraquat. The formation was demonstrated by spin trapping on illumination of spinach chloroplasts in the presence of oxygen and paraquat Superoxide radicals are formed, moreover, in the near-ultraviolet photooxidation of tryptophan, as indicated by the increase of the HjO production in the presence of SOD and on irradiation in aerated solutions of protoporphyrin at 400 nm and of melanin with light of 320—600nmas shown by spintrapping. 

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). 

Among the more interesting applications of polymer Rose Bengal is that of a sensitizer in studying the oxidation of other polymeric substrates [301]. Rose Bengal immobilized on Sepharose has been reported as a sensitizer for protein photooxidation [302], The oxygen uptake by the amino acids cysteine, hisitidine, methionine, tryptophan, and tyrosine was reported to be about 20% as much from the immobilized dye as from the free dye in aqueous solution. 

Photooxidation of alkaline phosphatase in the presence of methylene blue and Rose Bengal causes loss of activity for both native and apo-enzyme. In the case of the native enzyme, zinc protects 2 to 3 of the 16 histidine residues. The rate of oxidation of tryptophan is not affected by zinc, and there was no loss of tyrosine. Also, photooxidation of the apoenzyme diminishes zinc binding. It would appear that histidine residues play a role in binding the two zinc ions necessary for enzymic activity (91). 

Figure 18. Photooxidation pathways for histidine (1), tyrosine (2), tryptophan (3), ana methionine (4) (16). Wavy lines through structures indicate ring scissions. Cysteine is oxidized to cystine, in some cases, without sensitizing dye cystine may...

Competition between Type I and Type II photooxidations are affected by micellar media. Type I photooxidation involves initial quenching of the sensitizer excited state by substrate, while Type II photooxidations involve initial quenching of the sensitizer excited state by oxygen. Since, competition between Types I and II photooxidations are altered by the concentration of the substrate, local concentration effects in micelles play an important role. The photooxidation of tryptophan and tryptamine... 

Pyrene can sensitize the photooxidation of 1,3-diphenylisobenzofuran (72) in DTAC micellar solutions 61>. The reaction involves sensitization of singlet oxygen by pyrene which diffuses into another micelle and reacts with (72). Indole and tryptophan, which also react with singlet oxygen, quench the above reaction in ethanol solutions. However, in micellar systems they enhance the rate of reaction. Because of the high local concentrations of the quencher, the pyrene excited state is quenched by indole and tryptophan which leads to the photooxidation of (72) by a Type I process. 

Accordingly, Hammett constants or combinations of the argnments a and b can be used to estimate both complex stabilities of substituted aromatics with donor site atoms other than C in biology/biochemistry. Therefore the connection between the rest of the protein and tyrosine phenolate, tryptophan indole or histidine imidazole moieties is taken to be one huge substituent (e.g. in the frequent cases where three histidine residues coordinate to one copper or zinc ion or with tyrosine residues in water photooxidation), possibly introducing charge effects by pH, phosphorylation ( P switch ) or by complexation of other metals like Ca on the outer periphery of the molecule. 

Amino acid IV solutions may be administered without photoprotection, although the photooxidation of some amino acids may occur. The most susceptible amino acids are cystine, histidine, methionine, tryptophan, and tyrosine. The photopro-tected storage of amino acid injection solutions is strongly recommended. 

When amino acids in parenteral solutions are exposed to relatively intense illumination for 24 hours, simulating phototherapy in neonatal nurseries, most individual amino acids decrease only slightly. Decreases in the concentrations of methionine, proline, tryptophan, and tyrosine are significantly greater in the presence of riboflavine. The observed decreases in amino acid concentrations are unlikely to be nutritionally important. However, in view of the possibility that photooxidation products may exert toxic effects, it is best to shield amino acid solutions containing vitamins from strong sources of UV-VIS irradiation (86). 

Tryptophan oxidizes primarily via reactive oxygen species, although it may occur as a result of photooxidation in the presence of dyes. Trp and Met are the only amino acids that are capable of being oxidized below pH 4. The primary oxidation products of Trp... 

Histidine is susceptible to oxidation in the presence of metals, primarily by reaction with singlet oxygen, and this constitutes a major cause of enzyme degradation. Both histidine and tryptophan are highly susceptible to photooxidation. 

Rannug A, Rannug U, Rosenkranz HS, Winqvist L, Westerholm R, et al. 1987. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J. Biol. Chem. 262 15422-27... 

Helferich W, Denison MS. 1991. Photooxidized products of tryptophan can act as dioxin agonists. Molec. Pharmacol. 

The first step in XJVR-induced skin cancer is UVR-initiated DNA mutation, which causes the transformation of the normal cells to malignant cells. For UVR to initiate a biological reaction, it has to be absorbed by endogenous molecules (chromophores). UVB is absorbed directly by the DNA, and therefore can directly induce DNA mutation (224), in the form of thymine dimer formation (289). Some protein components may also ad as chromophores for UVB (224). UVA is absorbed by the reduced forms of the co-enzymes nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), tryptophan, riboflavin, and melanin (224,290). UVA-induced DNA damage is believed to be mediated by oxygen reactive species that are released after the absorption of UVA by those endogenous chromophores and results in photooxidation of selected bases... 

In view of the current interest in hydroxylation reactions in vivo it is to be hoped that this stage of tryptophan metabolism will receive more detailed attention from enzymologists. At present it can be stated definitely only that kynurenine (or possibly a derivative such as A -acetylkynurenine 170, 173) is converted either to hydroxykynurenine or to some simple derivative at the same level of oxidation. It is of interest that both kynurenine and hydroxykynurenine are formed on photooxidation of tryptophan, especially in the presence of ferrous iron (972). 

E. Reddi, M.A.J. Rodgers, J.D. Spikes, G. Jori (1984). The effect of medium polarity on the hematoporphyrin-sensitized photooxidation of L-tryptophan. Photochem. Photobiol, 40,415-421. 

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