Inoue Sadako, Kitajima Ken
Bioscience and Biotechnology Center, Nagoya University, Nagoya 464-8601, Japan.
Glycoconj J. 2006 Jul;23(5-6):277-90. doi: 10.1007/s10719-006-6484-y.
KDN is an abbreviation for 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid, and its natural occurrence was revealed in 1986 by a research group including the present authors. Since sialic acid was used as a synonym for N-acylneuraminic acid at that time, there was an argument if this deaminated neuraminic acid belongs to the family of sialic acids. In this review, we describe the 20 years history of studies on KDN (KDNology), through which KDN has established its position as a distinct member of the sialic acid family. These studies have clarified that: (1) KDN occurs widely among vertebrates and bacteria similar to the occurrence of the more common sialic acid, N-acetylneuraminic acid (Neu5Ac), but its abundant occurrence in animals is limited to lower vertebrates. (2) KDN is found in almost all types of glycoconjugates, including glycolipids, glycoproteins and capsular polysaccharides. (3) KDN residues are linked to almost all glycan structures in place of Neu5Ac. All linkage types known for Neu5Ac; alpha2,3-, alpha2,4-, alpha2,6-, and alpha2,8- are also found for KDN. (4) KDN is biosynthesized de novo using mannose as a precursor sugar, which is activated to CMP-KDN and transferred to acceptor sugar residues. These reactions are catalyzed by enzymes, some of which preferably recognize KDN, but many others prefer Neu5Ac to KDN. In addition to these basic findings, elevated expression of KDN was found in fetal human red blood cells compared with adult red blood cells, and ovarian tumor tissues compared with normal controls. KDNase, an enzyme which specifically cleaves KDN-linkages, was discovered in a bacterium and monoclonal antibodies that specifically recognize KDN residues in KDNalpha2,3-Gal- and KDNalpha2,8-KDN-linkages have been developed. These have been used for identification of KDN-containing molecules. Based on past basic studies and variety of findings, future perspective of KDNology is presented.
KDN是2-酮-3-脱氧-D-甘油-D-半乳糖壬糖酸的缩写，1986年一个包括本文作者在内的研究小组发现了它的天然存在。由于当时唾液酸被用作N-酰基神经氨酸的同义词，因此对于这种脱氨基神经氨酸是否属于唾液酸家族存在争议。在这篇综述中，我们描述了KDN研究的20年历史（KDN学），通过这段历史，KDN已确立其作为唾液酸家族独特成员的地位。这些研究阐明了：（1）KDN在脊椎动物和细菌中广泛存在，类似于更常见的唾液酸N-乙酰神经氨酸（Neu5Ac）的存在，但它在动物中的大量存在仅限于低等脊椎动物。（2）KDN几乎存在于所有类型的糖缀合物中，包括糖脂、糖蛋白和荚膜多糖。（3）KDN残基几乎取代Neu5Ac连接到所有聚糖结构上。Neu5Ac已知的所有连接类型；α2,3-、α2,4-、α2,6-和α2,8-在KDN中也能找到。（4）KDN从头合成，以甘露糖作为前体糖，其被激活为CMP-KDN并转移到受体糖残基上。这些反应由酶催化，其中一些酶优先识别KDN，但许多其他酶更喜欢Neu5Ac而不是KDN。除了这些基本发现外，与成人红细胞相比，在胎儿人红细胞中发现KDN表达升高，与正常对照相比，在卵巢肿瘤组织中也发现KDN表达升高。在一种细菌中发现了一种特异性切割KDN连接的酶KDNase，并且已经开发出特异性识别KDNα2,3-Gal-和KDNα2,8-KDN连接中KDN残基的单克隆抗体。这些已被用于鉴定含KDN的分子。基于过去的基础研究和各种发现，本文介绍了KDN学的未来展望。
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