Abstract
Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by β-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; β-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R f value obtained (0.24–0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing β-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients.
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