Photo-oxidation of proteins and its role in cataractogenesis

Proteins comprise approximately 68% of the dry weight of cells and tissues and are therefore potentially major targets for photo-oxidation. Two major types of processes can occur with proteins. The first of these involves direct photo-oxidation arising from the absorption of UV radiation by the protein, or bound chromophore groups, thereby generating excited states (singlet or triplets) or radicals via photo-ionisation. The second major process involves indirect oxidation of the protein via the formation and subsequent reactions of singlet oxygen generated by the transfer of energy to ground state (triplet) molecular oxygen by either protein-bound, or other, chromophores. The basic principles behind these mechanisms of photo-oxidation of amino acids, peptides and proteins and the potential selectivity of damage are discussed. Emphasis is placed primarily on the intermediates that are generated on amino acids and proteins, and the subsequent reactions of these species, and not the identity or chemistry of the sensitizer itself, unless the sensitizing group is itself intrinsic to the protein. A particular system is then discussed – the cataractous lens – where UV photo-oxidation may play a role in the aetiology of the disease, and tryptophan-derived metabolites act as UV filters.