Reconsidering the role of protein glycation in disease by Marissa N. Trujillo & James J. Galligan instant download

Reconsidering the role of protein glycation in disease by Marissa N. Trujillo & James J. Galligan instant download

Protein glycation has long-been considered In this Comment, we present an emerging paradigm that supports a hormetic role for protein glycation, extending beyond a toxic consequence of carbohydrate its designation as a simple measure of ‘sugar toxicity’. This field has metabolism. Yet recent evidence demonstrates drawn notable parallels to that of protein oxidation, which was long believed to serve as a measure of oxidative stress and protein damage8. tight regulation for these non-enzymatic It was not until appropriate study designs were established that reactive post-translational modifcations, pointing to a oxygen species (ROS) gained an appreciated homeostatic role in the broader role in cell biology rather than simply regulation of numerous cellular processes, including metabolic flux and transcriptional responses to cellular redox status8. Here, we opine serving as a biomarker for toxicity.that glycation should be evaluated in the same vein as other canonical PTMs, including protein oxidation, in which dose and context should Post-translational modifications (PTMs) provide a rapid response to be taken into consideration.regulate protein structure and function, expanding the functional A historical perspectiveproteome to maintain homeostasis. Although many PTMs are added to proteins through controlled, enzyme-catalyzed reactions, there is In the early twentieth century, there was growing interest in the physimounting evidence that many PTMs occur by non-enzymatic means1. ological role of α-oxoaldehydes and their metabolic regulation. These One of the most well-documented cases of a catalysis-free PTM is the reactive intermediates were initially proposed to be toxic by-products covalent attachment of a reducing sugar to a nucleophilic amino acid1. of metabolism owing to their reactivity with DNA, RNA and proteins9. Since its initial discovery, protein glycation has become an important Arguably, the most pre