Studies on the function and biosynthesis of oxodesmosine, new cross-linking amino acid of elastin

弹性蛋白是一种结缔组织蛋白，几乎存在于成熟动物的每一个组织和器官中，是血管、某些韧带和其他顺应性组织（如肺和皮肤）的主要成分。弹性蛋白主要是在生理发育过程中由血管平滑肌和成纤维细胞等细胞合成的，作为可溶性前体，弹力蛋白。每个对流层蛋白分子中有几对脱胺赖氨酸残基参与一系列自发缩合反应，从而形成交联氨基酸。本实验从牛主动脉弹性蛋白中分离出两个具有n取代二氢氧吡啶结构的新交联氨基酸，分别命名为oxodesmosine和isoxodesmosine。氧葡萄糖葡萄糖和异葡萄糖葡萄糖葡萄糖都具有很强的吸湿性，是带淡黄色的白色固体，可溶于水溶剂。通过紫外、核磁共振和质谱对这两种氨基酸进行了结构分析。从n -取代二氢氧吡啶骨架的结构可以推断，这两种新氨基酸是主要的吡啶交联氨基酸、氨基葡萄糖和异氨基葡萄糖的代谢中间体。这两种氨基酸在体内的合成可能是通过桥糖和异桥糖作为进一步分解这种交联的中间物的氧化进行的。虽然力学细节尚不清楚，但必须在酸水解过程中调用环化反应，伴随脱羧反应形成环戊烯骨架。

Elastin is one of the connective tissue protain found in virtually every tissue and organs of mature animals and is major constituent of blood vessels and certain ligaments and other compliant tissues such as lung and skin. Elastin is primarily synthesized during physiological development by such cells as the vascular smooth muscle and fibroblast as a soluble precursor, tropoelastin. Several pairs of deaminated lysyl residues in each tropoelestin molecule are involved in a set of spontaneous condensation reactions that lead to the formation of crosslinking amino acids. In our experiments, we isolated two new crosslinking amino acids having N-substituted dihydrooxopyridine structure named oxodesmosine and isooxodesmosine from bovine aorta elastin. Both oxodesmosine and isooxodesmosine were very hygroscopic, white solid with faint yellow tinges, soluble in aqueous solvents. Structural analysis of both amino acids were done by UV, NMR and MS.It might be deduced from the structure of N-substituted dihydrooxopyridine skeleton that these new amino acids are metabolic intermediate of major pyridinium crosslinking amino acids, desmosine and isodesmosine. The in vivo synthesis of both amino acids were probably took place by oxydation of desmosine and isodesmosine as intermediate for further decompositions of such crosslinks. Although the mechanical details are not clear, one must invoke the cyclization, accompany with decarboxylation reaction during acid hydrolysis to form cyclopentene skeleton.