GLYCATION INDUCES EXPANSION OF THE MOLECULAR PACKING OF COLLAGEN
GLYCATION INDUCES EXPANSION OF THE MOLECULAR PACKING OF COLLAGEN
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DOI：
10.1016/0022-2836(88)90015-0
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发表时间：
1988-09-20
影响因子：
5.6
通讯作者：
EIKENBERRY, EF
中科院分区：
文献类型：
--
作者：
TANAKA, S;AVIGAD, G;EIKENBERRY, EF
大鼠尾腱暴露于还原糖导致糖与胶原蛋白的共价连接，这一过程称为糖化，并导致形成稳定的分子间交联。本文用X射线衍射法研究了大鼠尾腱胶原蛋白糖基化引起的晶体单位细胞的变化。核糖被选为大多数研究的模型化合物，因为它与蛋白质的反应比葡萄糖快，因此更便于实验室研究，但也使用葡萄糖和甘油醛。一个动力学模型描述的过程中的糖基化核糖和随后的交联形成已被开发。糖化导致超过12%的单位细胞，描述了大鼠尾腱胶原蛋白的三维结构的扩张。膨胀是在垂直于棒状分子的轴的方向上，表明胶原的分子间间距增加。因此，在体外大鼠尾腱胶原蛋白的结构显着改变糖化。扩张不是各向同性的，而是平行于（120）平面，这是胶原分子密集分布的准六边形结构的三个主要平面之一。据推测，这种膨胀是由重叠区中一个或至多几个特定分子间交联的形成引起的，所述交联作用将分子推开。胶原组织中类似的结构变化很可能是在自然衰老过程中由体内糖基化引起的，并且这些变化在慢性高血糖症（如与糖尿病相关的高血糖症）中加速。对糖化大鼠尾腱结构的分析可能为我们深入了解胶原蛋白的分子结构提供新的视角。
Exposure of rat tail tendon to a reducing sugar results in covalent attachment of the sugar to collagen, a process termed glycation, and leads to the formation of stable intermolecular cross-links. We have used X-ray diffraction to study the changes in the crystalline unit cell of rat tail tendon collagen brought about by glycation. Ribose was selected as a model compound for most of the study because its reaction with proteins is faster than that of glucose, and therefore more convenient for laboratory studies, but glucose and glyceraldehyde were used as well. A kinetic model describing the process of glycation by ribose and subsequent cross-link formation has been developed. Glycation resulted in an expansion by more than 12% of the unit cell that describes the three-dimensional structure of rat tail tendon collagen. The expansion was in a direction perpendicular to the axes of the rod-shaped molecules, indicating that the intermolecular spacing of the collagen increased. Thus, the structure of collagen in rat tail tendon is significantly altered by glycation in vitro. The expansion was not isotropic, but was directed parallel to the (120) planes, one of the three major planes of the quasi-hexagonal structure that is densely populated by collagen molecules. It is hypothesized that this expansion is brought about by the formation of one, or at most a few, specific intermolecular cross-links in the overlap zone that act to push the molecules apart. It is likely that similar structural changes in collagenous tissues are caused by glycation in vivo during the natural course of aging, and that these changes are accelerated in chronic hyperglycemia such as that associated with diabetes. Analysis of the structure of glycated rat tail tendon potentially can give us new insight into the detailed molecular structure of collagen.