Reactions of lipid-derived malondialdehyde with collagen

Malondialdehyde is a product of fatty acid oxidation (e.g. from low density lipoprotein) implicated in the damage of proteins such as collagen in the cardiovascular system (Chio, K. J., and Tappel, A. L. (1969) Biochemistry 8 , 2821-2827), Its concentration is raised in diabetic subjects probably as a side effect of increased protein glycation, Collagen has enzyme-catalyzed cross-links formed between its individual molecules that are essential for maintaining the structure and flexibility of the collagen fiber. The cross -link dehydro-hydroxylysinonorleucine reacts irreversibly with 10 mM malond ialdehyde at least 3 orders of magnitude faster than glucose reactions with lysine or arginine, such that there is little cross-link left after 1 h at 37 degrees C, Other cross-links and glycated elements of collagen are also vulnerable. Several possible products of malondialdehyde with collagen cro ss-links are proposed, and the potential involvement of collagenous histidi ne in these reactions is discussed. We have also isolated N-delta-(2-pyrimi dyl)-L-ornithine from collagenous arginine reacted with malondialdehyde, Th e yields of this product were considerably higher than those from model rea ctions, being approximately 2 molecules/collagen molecule after 1 day at 37 degrees C in 10 mM malondialdehyde, Collagenous lysine-derived malondialde hyde products may have been present but were not protected from protein aci d hydrolysis by standard reduction techniques, thus resulting in a multitud e of fragmented products.