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从甲基乙二醛到丙酮酸:在高粱中鉴定醛氧化酶和 D-乳酸脱氢酶的全基因组研究。

From methylglyoxal to pyruvate: a genome-wide study for the identification of glyoxalases and D-lactate dehydrogenases in Sorghum bicolor.

机构信息

International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi, 110067, India.

School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.

出版信息

BMC Genomics. 2020 Feb 10;21(1):145. doi: 10.1186/s12864-020-6547-7.

Abstract

BACKGROUND

The glyoxalase pathway is evolutionarily conserved and involved in the glutathione-dependent detoxification of methylglyoxal (MG), a cytotoxic by-product of glycolysis. It acts via two metallo-enzymes, glyoxalase I (GLYI) and glyoxalase II (GLYII), to convert MG into D-lactate, which is further metabolized to pyruvate by D-lactate dehydrogenases (D-LDH). Since D-lactate formation occurs solely by the action of glyoxalase enzymes, its metabolism may be considered as the ultimate step of MG detoxification. By maintaining steady state levels of MG and other reactive dicarbonyl compounds, the glyoxalase pathway serves as an important line of defence against glycation and oxidative stress in living organisms. Therefore, considering the general role of glyoxalases in stress adaptation and the ability of Sorghum bicolor to withstand prolonged drought, the sorghum glyoxalase pathway warrants an in-depth investigation with regard to the presence, regulation and distribution of glyoxalase and D-LDH genes.

RESULT

Through this study, we have identified 15 GLYI and 6 GLYII genes in sorghum. In addition, 4 D-LDH genes were also identified, forming the first ever report on genome-wide identification of any plant D-LDH family. Our in silico analysis indicates homology of putatively active SbGLYI, SbGLYII and SbDLDH proteins to several functionally characterised glyoxalases and D-LDHs from Arabidopsis and rice. Further, these three gene families exhibit development and tissue-specific variations in their expression patterns. Importantly, we could predict the distribution of putatively active SbGLYI, SbGLYII and SbDLDH proteins in at least four different sub-cellular compartments namely, cytoplasm, chloroplast, nucleus and mitochondria. Most of the members of the sorghum glyoxalase and D-LDH gene families are indeed found to be highly stress responsive.

CONCLUSION

This study emphasizes the role of glyoxalases as well as that of D-LDH in the complete detoxification of MG in sorghum. In particular, we propose that D-LDH which metabolizes the specific end product of glyoxalases pathway is essential for complete MG detoxification. By proposing a cellular model for detoxification of MG via glyoxalase pathway in sorghum, we suggest that different sub-cellular organelles are actively involved in MG metabolism in plants.

摘要

背景

乙醛酸途径在进化上是保守的,参与了依赖谷胱甘肽的甲基乙二醛 (MG) 的解毒,MG 是糖酵解的细胞毒性副产物。它通过两种金属酶,即醛缩酶 I (GLYI) 和醛缩酶 II (GLYII),将 MG 转化为 D-乳酸,D-乳酸进一步被 D-乳酸脱氢酶 (D-LDH) 代谢为丙酮酸。由于 D-乳酸的形成仅通过醛缩酶酶的作用,因此其代谢可以被认为是 MG 解毒的最终步骤。通过维持 MG 和其他反应性二羰基化合物的稳态水平,乙醛酸途径作为生物体中糖基化和氧化应激的重要防御线。因此,考虑到醛缩酶在应激适应中的一般作用以及高粱能够耐受长时间干旱的能力,高粱乙醛酸途径值得深入研究,包括醛缩酶和 D-LDH 基因的存在、调控和分布。

结果

通过这项研究,我们在高粱中鉴定了 15 个 GLYI 和 6 个 GLYII 基因。此外,还鉴定了 4 个 D-LDH 基因,这是首次对任何植物 D-LDH 家族进行全基因组鉴定的报告。我们的计算机分析表明,推测的 SbGLYI、SbGLYII 和 SbDLDH 蛋白与拟南芥和水稻中几种功能上有特征的醛缩酶和 D-LDH 具有同源性。此外,这三个基因家族在其表达模式上表现出发育和组织特异性的变化。重要的是,我们可以预测推测的 SbGLYI、SbGLYII 和 SbDLDH 蛋白在至少四个不同的亚细胞隔室中的分布,即细胞质、叶绿体、细胞核和线粒体。高粱乙醛酸和 D-LDH 基因家族的大多数成员确实对胁迫高度敏感。

结论

这项研究强调了醛缩酶以及 D-LDH 在高粱中 MG 完全解毒中的作用。特别是,我们提出,代谢醛缩酶途径的特定终产物 D-LDH 对于完全 MG 解毒是必不可少的。通过提出高粱中 MG 通过乙醛酸途径解毒的细胞模型,我们建议不同的亚细胞细胞器积极参与植物中 MG 的代谢。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d079/7011430/bd65c9360f2e/12864_2020_6547_Fig1_HTML.jpg

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