D-amino acid in elderly tissues
D-amino acid in elderly tissues
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DOI：
10.1248/bpb.28.1585
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发表时间：
2005-09-01
影响因子：
2
通讯作者：
Fujii, N
中科院分区：
文献类型：
--
作者：
Fujii, N
地球上所有的生物体都是由L-氨基酸和D-糖组成的。因此，D-氨基酸在生物体中的存在和功能尚未研究。然而，最近，在来自人组织样品如老年人的眼透镜、脑、皮肤、骨、牙齿、主动脉的各种蛋白质中检测到D-天冬氨酸（D-Asp），其为D-氨基酸。已经解释了D-Asp的存在是在寿命期间蛋白质中Asp残基外消旋化的结果，因为这些组织中的蛋白质是代谢惰性的。来自老年人透镜的α A-晶状体蛋白中的Asp-151和Asp-58残基尤其是立体化学不稳定的，并且这些残基的D/L比大于1.0。D/L比大于1.0不定义为外消旋化，而是定义为构型反转。这是第一次观察到在自然老化过程中，体内氨基酸构型发生了反转。本文综述了近年来有关D-Asp在各种组织中的研究进展，并对D-Asp在蛋白质中的形成机制进行了阐述。我们认为，在蛋白质的天然高级结构中存在着一个手性反应场，它诱导了L-Asp向D-Asp残基的转化。
All living organisms on earth are composed of L-amino acids and D-sugars. Therefore the presence and function of D-amino acids in living organisms have not been studied. Recently, however, D-aspartic acid (D-Asp) which is a D-amino acid, has been detected in various proteins from human tissue samples such as eye lens, brain, skin, bone, teeth, aorta from elderly individuals. It has been explained that the presence of D-Asp is the result of racemization of Asp residues in the protein during the life span, inasmuch as the proteins in these tissues are metabolically inert. The Asp-151 and Asp-58 residues in alpha A-crystallin from elderly human lens are especially stereochemically labile and the D/L ratios of these residues were greater than 1.0. A D/L ratio greater than 1.0 is not defined as racemization, but as the inversion of configuration. This was the first observation that inversion occurred in the configuration of amino acids in vivo during the natural aging process. In this review, we summarize the D-Asp in the various tissues reported by many researchers and describe the mechanism of D-Asp formation in protein. We suggest that a chiral reaction field exists in the native higher order structure of protein which induces the inversion of L-Asp to D-Asp residue.