Identification of a new cross-link and unique histidine adduct from bovine serum albumin incubated with malondialdehyde.
Malondialdehyde, acetaldehyde, acrolein, and 4-hydroxynonenal are all products of fatty acid oxidation found in the fatty streaks of atherosclerotic arteries due to a lack of antioxidants and an increase in glycation products. Previously identified cross-links derived from these molecules have nearly always required more than one molecule of each type, although this is physiologically less likely than a reaction involving a single molecule. Here we provide indirect but strong evidence for a malondialdehyde-derived cross-link requiring just one malondialdehyde molecule to link arginine and lysine, giving 2-ornithinyl-4-methyl(1epsilon-lysyl)1,3-imidazole following a 4-day incubation of albumin with 8 mm malondialdehyde. This cross-link was identified as its partial degradation product Nepsilon-(2-carboxyl,2-aminoethane)-Nepsilon-methanoyl-lysine by NMR and mass spectrometry. Analysis of plasma from treated diabetic patients revealed that one patient levels had as high as 0.46%, 0.67% of their lysine/arginine residues modified by this cross-link, although others had lower levels. Alkaline hydrolysis of serum albumin also revealed two acid-labile malondialdehyde adducts of histidine in significant quantities, the isomers 4- and 2-ethylidene-histidine. These constituted up to 0.93% of the histidines in treated diabetic patients. Although collagen is readily cross-linked by malondialdehyde, none of these particular products could be found in incubations of collagen with malondialdehyde.
Slatter
David A
DA
Collagen Research Group, Division of Molecular and Cellular Biology, University of Bristol, Bristol BS40 5DS, UK. das55@cam.ac.uk
Avery
Nicholas C
NC
Bailey
Allen J
AJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001665:Binding Sites; D002417:Cattle; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood; D006168:Guinea Pigs; D006639:Histidine; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008315:Malondialdehyde / Q000494:pharmacology*; D013058:Mass Spectrometry; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000187:drug effects
D003432:Cross-Linking Reagents; D012710:Serum Albumin, Bovine; D006639:Histidine; D008315:Malondialdehyde; D001120:Arginine; D008239:Lysine