近日，英国剑桥大学的Markus Ralser研究组发现赖氨酸摄入是细胞中的抗氧化策略并引发细胞内多胺的合成。2019年8月8日出版的国际知名学术期刊《自然》发表了这一成果。

研究人员揭示了在应激情况下多胺和赖氨酸代谢之间的联系，其中多胺途径的第一个酶Spe1p对赖氨酸脱羧，然后形成另一种多胺（尸胺）。这一反应的进行依赖于细胞外赖氨酸的存在，细胞通过摄入超过生长所需浓度100倍的赖氨酸来达到反应所需浓度。这种大量的摄入没有在其他氨基酸中观察到，而是依赖于多胺途径并引发氧化还原代谢的重塑。因此，本应该在赖氨酸生物合成所需的NADPH引流到谷胱甘肽合成中，导致了谷胱甘肽浓度的大幅增加，从而降低了活性氧的水平并增加了氧化耐受。他们的研究结果表明，营养吸收的发生不仅促进细胞生长，也在营养供应充足时使细胞重塑其代谢从而预防性地增加压力保护。

研究人员表示，单细胞和多细胞生物依赖于抗应激机制来应对环境中的突然变化，这包括暴露于高温和氧化剂。应激反应的核心在与代谢的动态变化，如从糖酵解转换为磷酸戊糖途径（应对氧化压力的保守一线反应）。研究人员发现了在压力的情况下保护微生物细胞的第二种代谢适应。酵母多胺转运蛋白Tpo1p在维持抗氧化性方面的作用尚不清楚。然而，蛋白质组学时序实验表明其与赖氨酸代谢有关联。

附：英文原文

Title: Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism

Author: Viridiana Olin-Sandoval, Jason Shu Lim Yu, Leonor Miller-Fleming, Mohammad Tauqeer Alam, Stephan Kamrad, Clara Correia-Melo, Robert Haas, Joanna Segal, David Alejandro Pea Navarro, Lucia Herrera-Dominguez, Oscar Mndez-Lucio, Jakob Vowinckel, Michael Mlleder, Markus Ralser

Issue&Volume: Volume 572 Issue 7768

Abstract: Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathwaya conserved first-line response to oxidative insults. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p in maintaining oxidant resistance is unknown. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPHwhich would otherwise be required for lysine biosynthesisis channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.

DOI: 10.1038/s41586-019-1442-6

Source: https://www.nature.com/articles/s41586-019-1442-6