Comparative enzymology, biochemistry and pathophysiology of human exo-α-sialidases (neuraminidases)

被引:102
作者
Achyuthan, KE
Achyuthan, AM
机构
[1] ZymeTx Inc, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Dean McGee Eye Inst, Oklahoma City, OK 73104 USA
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY | 2001年 / 129卷 / 01期
关键词
human sialidase; human neuraminidase; sialic acid; biochemistry; pathophysiology; enzymology; molecular properties; deficiency and disease;
D O I
10.1016/S1096-4959(01)00372-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2001 Elsevier Science Inc. All rights reserved.
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页码:29 / 64
页数:36
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