Achyuthan K E, Achyuthan A M
ZymeTx Inc., 800 Research Parkway # 100, Oklahoma City, OK 73104, USA.
Comp Biochem Physiol B Biochem Mol Biol. 2001 May;129(1):29-64. doi: 10.1016/s1096-4959(01)00372-4.
This review summarizes the current research on human exo-alpha-sialidase (sialidase, neuraminidase). Where appropriate, the properties of viral, bacterial, and human sialidases have been compared. Sialic acids are implicated in diverse physiological processes. Sialidases, as enzymes acting upon sialic acids, assume importance as well. Sialidases hydrolyze the terminal, non-reducing, sialic acid linkage in glycoproteins, glycolipids, gangliosides, polysaccharides, and synthetic molecules. Therefore, a variety of assays are available to measure sialidase activity. Human sialidase is present in several organs and cells. Its cellular distribution could be cytosolic, lysosomal, or in the membrane. Human sialidase occurs in a high molecular-mass complex with several other proteins, including cathepsin A and beta-galactosidase. Multi-protein complexation is important for the in vivo integrity and catalytic activity of the sialidase. However, multi-protein complexation, the occurrence of isoenzymes, diverse subcellular localization, thermal instability, and membrane association have all contributed to difficulties in purifying and characterizing human sialidases. Human sialidase isoenzymes have recently been cloned and sequenced. Even though crystal structures for the human sialidases are not available, the highly conserved regions of the sialidase from various organisms have facilitated molecular modeling of the human enzyme and raise interesting evolutionary questions. While the molecular mechanisms vary, genetic defects leading to human sialidase deficiency are closely associated with at least two well-known human diseases, namely sialidosis and galactosialidosis. No therapy is currently available for either disease. A thorough investigation of human sialidases is therefore crucial to human health.
本综述总结了目前关于人类外切α-唾液酸酶（唾液酸酶、神经氨酸酶）的研究。在适当的地方，对病毒、细菌和人类唾液酸酶的特性进行了比较。唾液酸参与多种生理过程。唾液酸酶作为作用于唾液酸的酶，也具有重要意义。唾液酸酶可水解糖蛋白、糖脂、神经节苷脂、多糖和合成分子中末端的非还原唾液酸键。因此，有多种测定方法可用于测量唾液酸酶活性。人类唾液酸酶存在于多个器官和细胞中。其细胞分布可能是胞质、溶酶体或膜性的。人类唾液酸酶与其他几种蛋白质，包括组织蛋白酶A和β-半乳糖苷酶，以高分子量复合物的形式存在。多蛋白复合对于唾液酸酶在体内的完整性和催化活性很重要。然而，多蛋白复合、同工酶的存在、不同的亚细胞定位、热不稳定性和膜结合都导致了纯化和表征人类唾液酸酶的困难。人类唾液酸酶同工酶最近已被克隆和测序。尽管目前尚无人类唾液酸酶的晶体结构，但来自各种生物体的唾液酸酶的高度保守区域有助于对人类酶进行分子建模，并提出了有趣的进化问题。虽然分子机制各不相同，但导致人类唾液酸酶缺乏的遗传缺陷与至少两种著名的人类疾病密切相关，即唾液酸沉积症和半乳糖唾液酸沉积症。目前这两种疾病都没有治疗方法。因此，对人类唾液酸酶进行全面研究对人类健康至关重要。
