An analysis of the H2O2-mediated crosslinking of lens crystallins catalyzed by the heme-undecapeptide from cytochrome c.
In contrast to other tissues, the lens exists in a milieu containing relatively high (micromolar) concentrations of H2O2. It has been demonstrated that activation of H2O2 to more-potent oxidant species via the heme-undecapeptide from cytochrome c produces alterations in lens crystallin polypeptides similar to the changes found in cataract. These include crystallin polypeptide crosslinking and the development of a blue fluorescence not attributable to tryptophan. Of the three classes of mammalian crystallins, gamma-crystallin is crosslinked by heme peptide-H2O2, whereas alpha and beta are not. Heme peptide plus H2O2 generates dityrosine from free tyrosine, and, concomitant with crosslinking, the gamma-crystallin exposed to this system develops a new fluorophor with the the characteristics of dityrosine. The findings with bovine and human crystallins are identical in this regard. In addition to the oxidation of tyrosine, exposure to heme peptide-H2O2 results in the oxidation of tryptophan. The intrinsic fluorescence of alpha, beta, and gamma-crystallins is due primarily to tryptophan, and the intrinsic fluorescence of each is decreased by heme peptide-H2O2. Thus, tryptophan oxidation occurs in all crystallins, but crosslinking occurs only in gamma-crystallin and is associated with oxidation of tyrosine.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001704:Biopolymers; D002384:Catalysis; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D003459:Crystallins / Q000378:metabolism*; D006427:Hemin; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009842:Oligopeptides; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000596:Amino Acids; D001704:Biopolymers; D003459:Crystallins; D009842:Oligopeptides; C013994:ferri-heme undecapeptide; D014443:Tyrosine; D006427:Hemin; D014364:Tryptophan; D006861:Hydrogen Peroxide; C007543:dityrosine