Role of fructose in glycation and cross-linking of proteins

Abstract

Incubation of carbohydrate-free human serum albumin (HSA) with fructose in an aqueous buffer at pH 7.4 resulted in glycation of epsilon-amino groups of lysyl residues. A recently developed procedure, involving analysis of hexitol amino acids by high-performance liquid chromatography of phenylthiocarbamyl derivatives, was used to show that 85% of the bound hexose was attached to protein via carbon 2 (C-2). The remainder was attached to protein via carbon 1 (C-1). When incubations were conducted with glucose under identical conditions, all the hexose was attached via C-1. Examination of human ocular lens proteins showed that the majority of the covalently bound hexose was connected to epsilon-amino groups of lysyl residues via C-1; this was attributed mainly to nonenzymatic glucosylation in vivo, which has already been documented. A significant proportion (10-20%) of the bound hexose was connected via C-2. In view of the HSA-hexose incubation results (above), this indicated that the lens proteins had reacted with endogenous fructose; i.e., they had undergone nonenzymatic fructosylation in vivo. The model protein bovine pancreatic ribonuclease A reacted with fructose and glucose at similar rates under physiological conditions. However, covalent, non-disulfide cross-linking, which could be inhibited by D-penicillamine, was induced 10 times more rapidly by fructose than by glucose. It is postulated that some of the protein cross-linking that occurs in vivo is fructose-induced. The possible significance of these processes in diabetic subjects is discussed.

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

“…ApoA-I is the major protein constituent of HDL; however, the function and structure of apoA-I and HDL can be modified by non-enzymatic glycation to form advanced glycated end (AGE) products. It has been re-ported that fructose reacts with proteins at 37°C to produce colored, fluorescent derivatives (McPherson et al, 1988). In a previous report, we have shown that fructose-mediated apoA-I modification results in severe loss of several beneficial functions of apoA-I and HDL, producing pro-atherogenic and proaging molecules (Park et al, 2010a).…”

Specific detections of the early process of the glycation reaction by fructose and glucose in diabetic rat lens

“…In addition, fructose is known to be a more potent glycating agent than glucose because the population of its acyclic (open chain) form, which is the reactive species, is approximately 10 times that of glucose [7]. However, studies dealing with the fructation of proteins in vivo are few in number [8] because there is no reliable and simple method to quantitate the fructated proteins.…”

Advanced Glycation Endproducts form During Ovalbumin Digestion in the Presence of Fructose

“…In the case of glucose, the Schiff base then undergoes Amadori rearrangement to yield a more stable adduct. With fructose, the reaction is similar, but the reaction is termed as Heyns rearrangement (with carbon 2 instead of carbon 1 of the hexose) products and results in the formation of two products ( [10][11][12][13][14]). These early glycation products undergo further rearrangement, dehydration, and condensation reactions to produce irreversibly cross-linked, fluorescent derivatives, AGEs.…”