Can tryptophan oxidation lead to lower tryptophan level in diabetes? A commentary on 'Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine'.

摘要

Diabetes is associated with hyperglycemia and hyperketo-nemia, both of which generate reactive oxygen species [1-5]. A state of imbalance exists between oxidant stress and antiox-idative defense mechanisms that favors the former in diabetes. Accumulated oxidant stress can peroxidize the lipid and protein structure of the membrane bilayer, inducing a variety of cellular dysfunctions that lead ultimately to tissue pathology . There has been significant recent interest in oxidative stress and its role in the development of complications in diabetic patients [1-7]. No previous study has reported on the relationship between the oxidation of tryptophan and the altered function of protein molecules under hyperglycemic conditions. In mis issue of Free Radical Biology and Medicine, Chetyrkin and colleagues demonstrate that high levels of glucose can cause specific oxidative modification of tryptophan residues in lysozymes, thus inhibiting their activity. Similar modification of tryptophan residues has also been induced by the purified albumin-Amadori, a ribose-derived model glycation intermediate , This suggests that oxidative modification of tryptophan residues in protein occurs via either glucose or protein-Amadori intermediates and contributes to the altered function of the protein. This is an important finding with physiological significance. This study also showed that pyridoxamine can inhibit both tryptophan oxidation and functional protein damage. Both of these findings stimulate new research questions, such as, is tryptophan oxidation the culprit responsible for the reduced blood levels of tryptophan in experimental models of diabetes, as well as in diabetic patients [9,10]? The second question is whether pyridoxamine supplementation can normalize the blood levels of tryptophan in diabetes.