Endogenous Advanced Glycoxidation End Products Formation

It is now appreciated that normal living is associated with spontaneous chemical transformation of amine-containing molecules by reducing sugars in a process described since 1912 as the Maillard reaction. This process occurs constantly within the body and at an accelerated rate in diabetes (5,6). Reducing sugars react in a nonenzymatic way with free amino groups of proteins, lipids, and guanyl nucleotides in DNA and form Schiff base adducts. These further rearrange to form Amadori products, which undergo rearrangement, dehydration, and condensation reactions leading to the formation of irreversible moieties called AGEs. Among all naturally occurring sugars, glucose exhibits the slowest glycation rate, although intracellular sugars such as fructose, threose, glucose-6-phosphate, and glyceraldehyde-3-phosphate form AGEs at a much faster rate (5,6,14).

Faster and more efficient than the modification of proteins is the glycoxidation of lipids that contain free amines producing advanced lipoxidation end-products (5,6,15) (Fig. 1). AGEs such as eN-carboxymethyl-lisine (CML) can also form through autoxidation of glucose or ascorbate (16,17). Metal-catalyzed autoxidation of glucose is accompanied by the generation of reactive oxygen species as superoxide radicals, which can undergo dismutation to hydrogen peroxides (18). Physiological glycation processes also involve the modification of proteins by reactive oxoaldehydes that come from the degradation of glucose, Schiff base adducts, Amadori products, glycolytic intermediates, and lipid peroxidation. Among them, glyoxal, methylglyoxal (MG), and 3-deoxyglu-cosone have been more extensively studied. Under normal conditions, in vivo produced oxoaldehydes are metabolized and inactivated by enzymatic conversion to the corresponding aldonic acids and only a small portion proceeds to form AGEs (5,6,19).

Despite the identification of numerous AGE compounds that exist in nature the elucidation of the structure of pathogenic AGEs remains elusive. Pentosidine, CML, and MG derivatives are among the well-characterized compounds (5,6) that are commonly used as AGE markers in many studies. AGEs are immunologically distinct, but can co-exist on the same carrier proteins such as albumin, hemoglobin, collagen, or lipoproteins at different stages of the glycation process, some more unstable than others. This adds to the challenges presented to chemists and biologists interested in their characterization.

Fig. 1. Glycation and oxidation of lipids. Glycation of phospholipids containing a free amino group enhances the oxidation of the fatty acid chain (ref. 141).

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Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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