Formation of a phospholipid-linked pyrrolecarbaldehyde from model reactions of d-glucose and 3-deoxyglucosone with phosphatidyl ethanolamine Original Research Article

Phospholipid-linked ‘advanced glycation end products’ (AGEs) are supposed to play an important role for lipid oxidation in vivo. The identification of the pyrrolecarbaldehyde 1-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-4,10-dioxo-7-(tetradecanoyloxy)-3,5,9-trioxa-4λ5-phosphatricosan-4-olate () from model reactions of d-glucose or 3-deoxyglucosone (, 3-DG) with phosphatidyl ethanolamine (PE) is described. A preparation method is given for 1-(2-hydroxyethyl)-5-(hydroxymethyl)-1H-pyrrole-2-carbaldehyde (). Independent syntheses as well as unequivocal structural characterization are reported for the substitution products of 1-(2-hydroxyethyl)-5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde () and 5-(ethoxymethyl)-1-(2-hydroxyethyl)-1H-pyrrole-2-carbaldehyde (). For all these compounds, chromatographic and spectroscopic data were established by GLC–MS and HPLC with diode array detection (DAD). PE and d-glucose or 3-DG were either incubated at pH 7.4, 100 °C for 3 h or at pH 7.4, 37 °C for 5 weeks in neat buffer or ethanol–buffer mixtures. The phospholipid fraction was purified on a C18 solid-phase extraction column and cleaved with ethanolic potassium hydroxide. The carbaldehyde , released in this process, was identified by GLC–MS and quantified by HPLC–DAD. Formation of is favored in the ethanol–buffer reactions relative to those in buffer solution only although the amounts determined from the 37 °C incubations generally are very low. It seems likely, therefore, that phospholipid-linked pyrrolecarbaldehydes, such as , are biomarkers rather than effectors of membrane damage in vivo.