The Biosynthesis of Elastin Cross-links

Abstract

Recently, two new amino acids have been isolated from hydrolysates of bovine ligamenturn nuchae elastin by Partridge, Elsden, and Thomas (1).Further studies from the same laboratory (2) have shown the compounds to be structural isomers composed of a pyridinium ring with four side chains located at positions 1, 3, 4, and 5 (desmosine), as depicted in Fig. 1, or at positions 1, 2, 3, and 5 (isodesmosine).Each side chain has a carboxyl-terminal and an a-amino-terminal group, and since these amino acids were found in peptides containing multiple amino-and carboxyl-terminal groups (3), it has been proposed (2, 4) that either isomer could serve as a cross-link between as many as four different polypeptide chains.Consideration of the structure of the desmosinesi and the empirical formula (C&&N50~.H20) suggested that these compounds might arise from the condensation of the side chains of 4 lysine molecules with the loss of the e-amino group from 3 of them.Direct evidence that lysine serves as a precursor has been obtained from studies on the incorporation of radioactivity into the desmosines from lysine-14C (4, 5).Furthermore, we have found that the amino acid composition of chick aorta elastin remains constant with age except that there is an increase in the content of the desmosines accompanied by an equivalent decrease in lysine content (5).These results (4, 5) indicate that the conversion of lysine to the desmosines occurs after the incorporation of lysine into elastin or an elastin precursor.In this report, we examine in further detail the biosynthesis of the desmosines.Since copper deficiency is known to produce defects in aortic elastin (6-8) and since lathyrism has been shown to cause both an interference in the cross-linking of collagen (911) and degenerative changes in aortic elastin (12), we have also investigated the effect of these conditions.