Department of Biochemistry, University of Oulu, Finland.
Antioxid Redox Signal. 2012 May 15;16(10):1129-38. doi: 10.1089/ars.2011.4481. Epub 2012 Mar 2.
The biogenesis of most secreted and outer membrane proteins involves the formation of structure stabilizing disulfide bonds. Hence knowledge of the mechanisms for their formation is critical for understanding a myriad of cellular processes and associated disease states.
Until recently it was thought that members of the Ero1 sulfhydryl oxidase family were responsible for catalyzing the majority of disulfide bond formation in the endoplasmic reticulum. However, multiple eukaryotic organisms are now known to show no or minor phenotypes when these enzymatic pathways are disrupted, suggesting that other pathways can catalyze disulfide bond formation to an extent sufficient to maintain normal physiology.
This lack of a strong phenotype raises multiple questions regarding what pathways are acting and whether they themselves constitute the major route for disulfide bond formation. This review critically examines the potential low molecular oxidants that maybe involved in the catalyzed or noncatalyzed formation of disulfide bonds, with an emphasis on the mammalian endoplasmic reticulum, via an examination of their thermodynamics, kinetics, and availability and gives pointers to help guide future experimental work.
大多数分泌蛋白和外膜蛋白的生物发生都涉及形成结构稳定的二硫键。因此，了解它们形成的机制对于理解无数的细胞过程和相关的疾病状态至关重要。
直到最近，人们还认为 Ero1 巯基氧化酶家族的成员负责催化内质网中大多数二硫键的形成。然而，现在已知多种真核生物在这些酶途径被破坏时表现出无或轻微的表型，这表明其他途径可以催化二硫键形成，足以维持正常的生理功能。
这种弱表型缺乏提出了多个问题，即哪些途径在起作用，以及它们本身是否构成二硫键形成的主要途径。本文通过考察其热力学、动力学以及在哺乳动物内质网中的可用性，批判性地研究了可能参与二硫键催化或非催化形成的潜在低分子氧化剂，并为指导未来的实验工作提供了线索。
