Glucosepane - Accumulation

Accumulation

Glycation processes that lead to AGEs particularly affect long-lived proteins in the human body, such as collagen in the skin and crystallin in the eyes. Skin collagen, for instance, has a half-life of fifteen years. Because these proteins do not degrade as quickly as other proteins in the body, the Amadori product, which is stable and thus transforms very slowly, has time enough to convert into glucosepane. It has been estimated that 50-60% of the steady state levels of Amadori product is converted into glucosepane in old age. A suspected reason for the prevalence of the glucosepane cross-link product as opposed to others is that the α−dicarbonyl from which it forms, N 6-(2,3-dihydroxy-5,6-dioxohexyl)-L-lysinate, is a persisting glycating agent because it is irreversibly bound through lysine to a protein. Therefore, it is not easily degraded and thus is more commonly available to form a cross-link with arginine, unlike other cross-link a-dicarbonyl intermediates, which are found bound and free and thus more susceptible to being degraded by enzymes in the ECM.

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