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 in 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 acids and a mass of 396 (C(18)H(28)N(4)0(6)) 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 cross-links desmopyridine (DESP) and isodesmopyridine (IDP), respectively. Structure analysis of these pyridine cross-links implied that the formation of these cross-links involved the condensation reaction between ammonia and allysine. The elastin incubated with ammonium chloride showed that DESP and IDP levels increased as the allysine content decreased. DESP and IDP were measured by high pressure liquid chromatography (HPLC) with UV detection and were found in a variety of bovine tissues. The DESP/desmosine (DES) and IDP/isodesmosine (IDE) ratios in aorta elastin were higher than in other tissues. DESP and IDP contents in human aorta elastin were found to be gradually increased with age. The concentration of IDP was significantly elevated in aorta elastin of rat with chronic liver cirrhosis induced by carbon tetrachloride (mean +/- S.D.; 11.1 +/- 0.9 nmol/mg elastin) when compared with normal 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-links may be useful biomarkers for the aortic elastin damaged by ammonia.
Department of Applied Bioorganic Chemistry, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
H
H
Umeda
M
M
Takeuchi
K
K
Suyama
D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D000375:Aging; D000596:Amino Acids / Q000737:chemistry* / Q000302:isolation & purification; D000643:Ammonium Chloride; D000818:Animals; D001011:Aorta / Q000737:chemistry; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D004549:Elastin / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000473:pathology; D008168:Lung / Q000737:chemistry; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D011725:Pyridines / Q000737:chemistry* / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D000596:Amino Acids; D003432:Cross-Linking Reagents; D011725:Pyridines; C426671:desmopyridine; C426672:isodesmopyridine; D000643:Ammonium Chloride; D015074:2-Aminoadipic Acid; C000061:allysine; D004549:Elastin