McCall A Scott, Cummings Christopher F, Bhave Gautam, Vanacore Roberto, Page-McCaw Andrea, Hudson Billy G
Department of Pharmacology, Vanderbilt University School of Medicine, 451 Preston Research Building, Nashville, TN 37232, USA.
Department of Biochemistry, Vanderbilt University School of Medicine, 607 Light Hall, Nashville, TN 37232, USA; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, D-3100 Medical Center North, Nashville, TN 37232, USA.
Cell. 2014 Jun 5;157(6):1380-1392. doi: 10.1016/j.cell.2014.05.009.
Bromine is ubiquitously present in animals as ionic bromide (Br(-)) yet has no known essential function. Herein, we demonstrate that Br(-) is a required cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a posttranslational modification essential for tissue development and architecture found within the collagen IV scaffold of basement membranes (BMs). Bromide, converted to hypobromous acid, forms a bromosulfonium-ion intermediate that energetically selects for sulfilimine formation. Dietary Br deficiency is lethal in Drosophila, whereas Br replenishment restores viability, demonstrating its physiologic requirement. Importantly, Br-deficient flies phenocopy the developmental and BM defects observed in peroxidasin mutants and indicate a functional connection between Br(-), collagen IV, and peroxidasin. We establish that Br(-) is required for sulfilimine formation within collagen IV, an event critical for BM assembly and tissue development. Thus, bromine is an essential trace element for all animals, and its deficiency may be relevant to BM alterations observed in nutritional and smoking-related disease. PAPERFLICK:
溴以离子态溴化物（Br(-)）的形式普遍存在于动物体内，但目前尚未发现其具有已知的基本功能。在此，我们证明Br(-)是过氧化物酶催化形成亚磺酰亚胺交联所必需的辅助因子，亚磺酰亚胺交联是一种翻译后修饰，对组织发育和结构至关重要，存在于基底膜（BM）的IV型胶原支架中。溴化物转化为次溴酸后，形成溴鎓离子中间体，该中间体在能量上有利于亚磺酰亚胺的形成。果蝇饮食中缺乏溴是致命的，而补充溴可恢复其活力，证明了其生理需求。重要的是，缺乏溴的果蝇表现出与过氧化物酶突变体中观察到的发育和BM缺陷相似的表型，表明Br(-)、IV型胶原和过氧化物酶之间存在功能联系。我们确定Br(-)是IV型胶原中亚磺酰亚胺形成所必需的，这一事件对BM组装和组织发育至关重要。因此，溴是所有动物必需的微量元素，其缺乏可能与营养和吸烟相关疾病中观察到的BM改变有关。快速浏览：
