Two new elastin cross-links having pyridine skeleton - Implication of ammonia in elastin cross-linking in vivo

Isolation and structure analysis of two amino acids from bovine ligamentum nuchae elastin hydrolysates revealed the presence of pyridine cross-links i n elastin. The structures of these amino acids were determined to have 3,4, 5- and 2,3,5-trisubstituted pyridine skeletons both with three carboxylic a cids and a mass of 396 (C18H28N4O6) identified as 4-(4-amino-4-carboxybutyl )3,5-di-(3-amino-3-carboxypropyl)-pyridine and 2-(4-amino-4-carboxybutyl)-3 ,5-di-(3-amino-3-carboxypropyl)-pyridine, We have named these pyridine cros s-links desmopyridine (DESP) and isodesmopyridine (IDP), respectively. Stru cture analysis of these pyridine crosslinks implied that the formation of t hese cross-links involved the condensation reaction between ammonia and all ysine. The elastin incubated with ammonium chloride showed that DESP and ID P levels increased as the allysine content decreased. DESP and IDP were mea sured by high pressure liquid chromatography (HPLC) with W detection and we re found in a variety of bovine tissues. The DESP/desmosine (DES) and IDP/i sodesmosine (IDE) ratios in aorta elastin were higher than in other tissues . DESP and IDP contents in human aorta elastin were found to be gradually i ncreased with age. The concentration of IDP was significantly elevated in a orta elastin of rat with chronic liver cirrhosis induced by carbon tetrachl oride (mean +/- S.D.; 11.1 +/- 0.9 nmol/mg elastin) when compared with norm al rats (5.9 +/- 1.5 nmol/mg elastin), Although DESP and IDP are present at only trace concentrations in the tissue elastin, these pyridine cross-link s may be useful biomarkers for the aortic elastin damaged by ammonia.