Formation of a phospholipid-linked pyrrolecarbaldehyde from model reactions of D-glucose and 3-deoxyglucosone with phosphatidyl ethanolamine.
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)-1 H-pyrrol-1-yl]-4,10-dioxo-7-(tetradecanoyloxy)-3,5,9-trioxa- 4lambda5-phosphatricosan-4-olate (7) from model reactions of D-glucose or 3-deoxyglucosone (4, 3-DG) with phosphatidyl ethanolamine (PE) is described. A preparation method is given for 1-(2-hydrox¿ethyl)-5-(hydroxymethyl)-1H-pyrrole-2-carbaldehyde (8). Independent syntheses as well as unequivocal structural characterization are reported for the substitution products of 8 1-(2-hydroxyethyl)-5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (9a) and 5-(ethoxymethyl)-1-(2-hydroxyethyl)-1H-pyrrole-2-carbaldehyde (9b). 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 4 were either incubated at pH 7.4, 100 degrees C for 3 h or at pH 7.4, 37 degrees 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 8, released in this process, was identified bs GLC-MS and quantified by HPLC-DAD. Formation of 7 is favored in the ethanol buffer reactions relative to those in buffer solution only although the amounts determined from the 37 degrees C incubations generally are very low. It seems likely, therefore, that phospholipid-linked pyrrolecarbaldehydes, such as 7, are biomarkers rather than effectors of membrane damage in vivo.
Lederer
M O
MO
Institut für Lebensmittelchemie, Universität Hohenheim, Stuttgart, Germany. ledererm@uni-hohenheim.de
Baumann
M
M
D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D000447:Aldehydes; D010714:Phosphatidylethanolamines; C002986:2-pyrrolecarboxylic acid; D011392:Proline; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D005947:Glucose