Metabolism of amyloid proteins.
Metabolism of amyloid proteins.
复制标题
淀粉样蛋白的代谢。
DOI：
10.1002/9780470514924.ch7
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Uemichi,T
中科院分区：
文献类型：
--
作者：
Benson,MD;Kluve-Beckerman,B;Liepnieks,JJ;Murrell,JR;Hanes,D;Uemichi,T
淀粉样前体蛋白的代谢加工是几乎所有形式淀粉样变性发生的重要因素。在系统性淀粉样变性的三种主要形式中，反应性淀粉样蛋白（淀粉样蛋白 A 蛋白；AA）的形成显示了血清淀粉样蛋白 A (SAA) 部分蛋白水解为形成原纤维的 AA 蛋白的最一致的作用。免疫球蛋白淀粉样变性通常也与原纤维前体轻链蛋白 C 端降解有关。尽管通常认为转甲状腺素蛋白淀粉样变性与四聚体循环血浆转甲状腺素蛋白原纤维形成有关，但转甲状腺素蛋白原纤维沉积物的化学分析显示原纤维蛋白成分的显着碎片化。此外，据记载，蛋白水解片段是凝溶胶蛋白、半胱氨酸蛋白酶抑制剂 C、阿尔茨海默病 β-淀粉样蛋白前体蛋白和载脂蛋白 AI (apoAI) 淀粉样变性中的原纤维亚基蛋白。蛋白水解在淀粉样原纤维形成中的作用的值得注意的例外是溶菌酶和β2-微球蛋白淀粉样变性。很少有研究检查淀粉样蛋白形成蛋白的代谢。也许最好的数据是 apoAI，它显示淀粉样变性 Gly26Arg apoAI 的血浆停留时间缩短（1.8 天，正常为 4.5 天）。同样，初步数据显示与野生型蛋白相比，Val30Met 运甲状腺素蛋白的清除率增加（18 小时与 26 小时）。此外，与小鼠 SAA1 相比，用 HDL 重建的生物合成 35 S 标记的 SAA 蛋白显示小鼠 SAA2（淀粉样原纤维亚基蛋白）的血浆清除率增加。关于淀粉样免疫球蛋白轻链蛋白代谢的数据很少，但已表明放射性标记的本斯-琼斯蛋白从循环中被非常迅速地清除。更好地了解每种淀粉样蛋白沉积疾病中前体蛋白的代谢将有助于深入了解原纤维形成的机制和淀粉样变性的发病机制。
Metabolic processing of amyloid precursor proteins is an important factor in the genesis of practically all forms of amyloidosis. Of the three major forms of systemic amyloidosis, reactive amyloid (amyloid A protein; AA) formation shows the most consistent role of partial proteolysis of serum amyloid A (SAA) to AA proteins which form fibrils. Immunoglobulin amyloidosis is also usually associated with C‐terminal degradation of the fibril precursor light chain protein. Although it is commonly thought that transthyretin amyloidosis is associated with fibril formation from the tetrameric circulating plasma transthyretin, chemical analyses of transthyretin fibril deposits show significant fragmentation of the fibril protein constituents. In addition, it has been documented that proteolytic fragments are the fibril subunit proteins in gelsolin, cystatin C, Alzheimer's β‐amyloid precursor protein and apolipoprotein AI (apoAI) amyloidoses. Notable exceptions to the role of proteolysis in amyloid fibril formation would appear to be the lysozyme and β2‐microglobulin amyloidoses. Few studies have examined the metabolism of amyloid‐forming proteins. Perhaps the best data are on apoAI, which show decreased plasma residence time for the amyloidogenic Gly26Arg apoAI (1.8 d vs. normal 4.5 d). Similarly, preliminary data show increased clearance of Val30Met transthyretin when compared with the wild‐type protein (18 h vs. 26 h). Also, biosynthetically35S‐labelled SAA proteins reconstituted with HDL show increased plasma clearance of murine SAA2, the amyloid fibril subunit protein, when compared with murine SAA1. Few data are available on metabolism of amyloid immunoglobulin light chain proteins, but it has been shown that radiolabelled Bence–Jones proteins are cleared very rapidly from the circulation. A better understanding of the metabolism of precursor proteins in each of the amyloid deposition diseases will give insight into the mechanisms of fibril formation and pathogenesis of amyloidosis.