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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Evidence that feedback inhibition of NAD kinase controls responses to oxidative stress
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Evidence that feedback inhibition of NAD kinase controls responses to oxidative stress

机译：反馈抑制NAD激酶控制对氧化应激反应的证据

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摘要

Formation of NADP(+) from NAD(+) is catalyzed by NAD kinase (NadK; EC 2.7.1.23). Evidence is presented that NadK is the only NAD kinase of Salmonella enterica and is essential for growth. NadK is inhibited allosterically by NADPH and NADH. Without effectors, NadK exists as an equilibrium mixture of dimers and tetramers (K-D = 1.0 +/- 0.8 mM) but is converted entirely to tetramers in the presence of the inhibitor NADPH. Comparison of NadK kinetic parameters with pool sizes of NADH and NADPH suggests that NadK is substantially inhibited during normal growth and, thus, can increase its activity greatly in response to temporary drops in the pools of inhibitory NADH and NADPH. The primary inhibitor is NADPH during aerobic growth and NADH during anaerobic growth. A model is proposed in which variation of NadK activity is central to the adjustment of pyridine nucleotide pools in response to changes in aeration, oxidative stress, and UV irradiation. It is suggested that each of these environmental factors causes a decrease in the level of reduced pyridine nucleotides, activates NadK, and increases production of NADF(H) at the expense of NAD(H). Activation of NadK may constitute a defensive response that resists loss of protective NADPH.
机译：NAD激酶（NadK; EC 2.7.1.23）催化从NAD（+）形成NADP（+）。有证据表明，NadK是肠炎沙门氏菌的唯一NAD激酶，并且对生长至关重要。 NadK被NADPH和NADH变构抑制。在没有效应子的情况下，NadK以二聚体和四聚体的平衡混合物形式存在（K-D = 1.0 +/- 0.8 mM），但在抑制剂NADPH存在下会完全转化为四聚体。将NadK动力学参数与NADH和NADPH库的大小进行比较表明，NadK在正常生长过程中受到了显着抑制，因此可以响应抑制性NADH和NADPH库中的暂时下降而大大提高其活性。主要抑制剂是有氧生长期间的NADPH和厌氧生长期间的NADH。提出了一个模型，其中NadK活性的变化对于响应曝气，氧化应激和紫外线照射的变化而对吡啶核苷酸库的调节至关重要。建议这些环境因素中的每一个都会导致还原的吡啶核苷酸水平降低，激活NadK并增加NADF（H）的产生，但以NAD（H）为代价。 NadK的激活可能构成防御性反应，可以抵抗保护性NADPH的丢失。

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