Diebold B A, Bokoch G M
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Nat Immunol. 2001 Mar;2(3):211-5. doi: 10.1038/85259.
A Rac GTPase-regulated multiprotein NADPH oxidase is critical for the formation of reactive oxygen species (ROS) in phagocytic leukocytes and other nonphagocytic cells. NADPH oxidase reduces molecular oxygen to form superoxide anion in a two-step process. Electrons are initially transferred from NADPH to cytochrome b-associated FAD, then to cytochrome b heme and finally to molecular oxygen. We show here that Rac is required for both electron-transfer reactions. Mutational and biophysical analysis shows that Rac and p67phox independently regulate cytochrome b to catalyze the transfer of electrons from NADPH to FAD. However, they must interact with each other to induce the subsequent transfer of electrons from FAD to cytochrome b heme and molecular oxygen. This two-step model of regulation by Rac GTPase may provide a means of more effectively controlling the inflammatory responses of phagocytic leukocytes.
一种由Rac GTP酶调节的多蛋白NADPH氧化酶对于吞噬性白细胞和其他非吞噬性细胞中活性氧（ROS）的形成至关重要。NADPH氧化酶通过两步过程将分子氧还原形成超氧阴离子。电子最初从NADPH转移到与细胞色素b相关的FAD，然后转移到细胞色素b血红素，最后转移到分子氧。我们在此表明，Rac对于这两个电子转移反应都是必需的。突变和生物物理分析表明，Rac和p67phox独立调节细胞色素b以催化电子从NADPH转移到FAD。然而，它们必须相互作用以诱导随后的电子从FAD转移到细胞色素b血红素和分子氧。这种由Rac GTP酶进行的两步调节模型可能提供一种更有效地控制吞噬性白细胞炎症反应的方法。
