The glucosylamine oxidation pathway of vitamin C recycling

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP is presented from the perspective of the hemoglobin glycation index, a clinically practical biomarker of risk for chronic vascular disease that we propose is mechanistically explained by person-to-person variation in GOP activity. •This report describes the glucosylamine oxidation pathway (GOP) of vitamin C recycling.•The GOP uses glucose and hemoglobin to reduce dehydroascorbic acid to ascorbic acid.•GOP activity is positively correlated with blood glucose concentration.•GOP activity is inversely related to erythrocyte glutathione concentration.•People with low GOP activity have greater risk for chronic vascular disease.