Quantification of N-(glucitol)ethanolamine and N-(carboxymethyl)serine: Two products of nonenzymatic modification of aminophospholipids formed in vivo

Chemical, nonenzymatic modification of protein and lipids by reducing sugar s, such as glucose, is thought to contribute to age-related deterioration i n tissue protein and cellular membranes and to the pathogenesis of diabetic complications. This report describes the synthesis and quantification of N -(glucitol)ethanolamine (GE) and N-(carboxymethyl)serine (CMS), two product s of nonenzymatic modification of aminophospholipids. GE is the product of reduction and hydrolysis of glycated phosphatidylethanolamine (PE), while C MS is formed through reaction of phosphatidylserine (PS) with products of o xidation of either carbohydrate (glycoxidation) or lipids (lipoxidation), G as chromatography/mass spectrometry procedures for quantification of the N, O-acetyl methyl ester derivatives of the modified head groups were develope d. GE and CMS were quantified in samples of PE and PS, respectively, follow ing incubation with glucose in vitro; CMS formation was dependent on the pr esence of oxygen during the incubation. Both GE and CMS were detected and q uantified in lipid extracts of human red blood cell membranes. The content of GE, but not CMS, was increased in the lipids from diabetic compared to n ondiabetic subjects. Measurement of these modified lipids should prove usef ul for assessing the role of carbonyl-amine reactions of aminophospholipids in aging and age-related diseases. (C) 1999 Academic Press.