Journal of Photochemistry and Photobiology B: Biology
Photo-oxidation of proteins and its role in cataractogenesis
Introduction
Proteins are major targets for photo-oxidation within cells due to their high abundance, the presence of endogenous chromophores within the protein structure (both amino acid side-chains and bound prosthetic groups such as flavins and heme), their ability to bind exogenous chromophoric materials, and their rapid rates of reaction with other excited state species. Photo-oxidation of proteins has been traditionally been defined as occurring via two major routes. The first of these is direct photo-oxidation arising from the absorption of UV radiation by the protein structure (primarily side-chains), or bound chromophores, thereby generating excited state species (singlet or triplets) or radicals as a result of photo-ionisation; these mechanisms are often referred to as Type 1 processes. The second major process involves indirect oxidation of the protein via the formation and subsequent reactions of singlet oxygen (molecular oxygen in its first excited singlet state, 1Δg O2 or 1O2) generated by the transfer of energy to ground state (triplet) molecular oxygen by either protein-bound, or other chromophores; these reactions are often referred to as Type 2 processes.
Section snippets
Ground state absorption spectra of amino acids, peptides and proteins
Direct oxidation of amino acids, peptides and proteins by UV light is only a significant process if the incident light is absorbed by the protein. For most proteins without bound (covalent or non-covalent) co-factors or prosthetic groups this only occurs with light with λ≤ca. 320 nm. The major chromophoric amino acids present in proteins are tryptophan (Trp), tyrosine (Tyr), phenylalanine (Phe), histidine (His), cysteine (Cys) and cystine; the UV spectra of these amino acids are given in Ref.
Formation and reactions of singlet states
The absorption of UV light by Trp, Tyr, His, Phe, Cys and cystine can give both excited state species and radicals via photo-ionisation (reviewed in Refs. [1], [3]). The relative energies of the short-lived first excited singlet states decrease in the order: Phe>Tyr>Trp [3], which can result in rapid energy transfer from Phe and Tyr to Trp. This is the reason why the fluorescence spectra of most proteins is often dominated by that of Trp. All three of these amino acids show broad featureless
Indirect (Type 2) photo-oxidation: formation and reactions of singlet oxygen
Photolysis of aromatic compounds (e.g., naphthalene and anthracene derivatives) or conjugated alkenes (e.g., porphyrins, a wide variety of dye molecules) generates excited states that can undergo rapid energy transfer with O2. Such reactions usually generate the first excited singlet state (1ΔgO2) of molecular oxygen. This state, which has both electrons in the same molecular orbital with paired spins, is formed readily, being only ca. 94 kJ mol−1 above the ground triplet state (3Σ), and has a
Physical and chemical consequences of photo-oxidation of proteins
Von Tappeiner in 1903, first established that exposure of enzymes to a photosensitizer in the presence of air and light resulted in loss of enzymatic or functional activity [57]. In the majority of studies on the 1O2-mediated oxidation of proteins the products have not been elucidated in a quantitative manner, though a number of studies have reported the formation of N-formylkynurenine and kynurenine from Trp [49], Met sulphoxide from Met [58], [59], and cystine from Cys [26]. In a number of
Human studies
The lens of the eye is designed to transmit light. Since we know, often from personal experience, e.g., sunburn, that solar radiation has the potential to damage biological tissues, it is but a short step to conclude that exposure to UV radiation over a lifetime may be responsible for the most common form of blindness: age related cataract. This hypothesis becomes more tenable when one appreciates that proteins in the bulk of the lens do not turn over; thus proteins in the centre of the lens
Acknowledgements
The authors would like to thank the Australian Research Council, the National Health and Medical Research Council, and the Wellcome Trust for financial support, and the members of the Australian Cataract Research Foundation who have been involved in some of the work reported here.
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