Regulation and Metabolic Networking of Leucine Catabolism

生物体维持合成代谢和分解代谢平衡的能力对于实现生物分子的净积累至关重要。此外，这种代谢平衡必须与生物体的其他代谢相结合，并保持灵活性，以响应各种各样的发育和环境信号。对于固定的生物，如植物，适应环境参数是特别重要的。对甲基巴豆酰辅酶a羧化酶（methylcrotonyl-CoA carboxyylase, MCCase）代谢功能的研究表明，植物亮氨酸分解代谢与其他代谢和生理过程是相互联系的。因此，对植物亮氨酸分解代谢的研究可能为生物体如何通过网络代谢来实现对复杂网状过程的多个水平的调节提供新的见解。本项目重点研究拟南芥中亮氨酸分解代谢的调控，作为如何控制复杂相互关联的代谢途径以实现生物分子净相互转换的一个例子。研究表明，植物通过线粒体途径分解亮氨酸，这需要MCCase酶。此外，mccase缺陷遗传群的特征表明，植物中的亮氨酸分解代谢在线粒体和过氧化物酶体之间共享。本项目的目的是阐明将亮氨酸分配给线粒体和过氧化物酶体分解代谢途径的信号和调节机制，并确定这些分解代谢途径如何与其他代谢过程联网。为了做到这一点，将测试三个特定的假设：假设1：线粒体亮氨酸分解代谢的阻断通过基因表达模式的全局变化来补偿。假设2:MCCase是亮氨酸分解代谢和类异戊二烯代谢的整合点。假设3：线粒体亮氨酸分解代谢受生物体代谢状态的调节，部分通过MCCase基因转录的变化。植物吸收简单的分子，如二氧化碳和水。利用来自太阳的能量，这些转化为复杂的化合物，如淀粉、蛋白质、纤维、油和药物。此外，这些复杂的化合物不断被分解，为生长提供能量，并提供每个植物细胞对不断变化的环境做出反应所需的新化合物。因此，植物对有用生物分子的净积累取决于两个过程之间的平衡。这项研究的长期目标是利用遗传和生化方法结合的内在协同作用，最终揭示植物如何维持这种平衡。

An organism's ability to maintain a balance between anabolism and catabolism is crucial to achieving net accumulation of biomolecules. In addition, this metabolic balance must be integrated with the rest of the organism's metabolism and remain flexible to respond to a wide variety of developmental and environmental signals. For stationary organisms such as plants, accommodation to environmental parameters is particularly critical. Research on the metabolic function of methylcrotonyl-CoA carboxylase (MCCase) indicates that plant leucine catabolism is networked with other metabolic and physiological processes. Hence, the study of plant leucine catabolism may offer novel insights on how organisms network metabolism to achieve several levels of regulation of complex reticulated processes. This project focuses on the regulation of leucine catabolism in Arabidopsis as an example of how complex interconnected metabolic pathways are controlled to achieve net interconversions of biomolecules. It has been shown that plants catabolize leucine via a mitochondrial pathway that requires the enzyme MCCase. In addition, characterizations of MCCase-deficient genetic stocks indicate that leucine catabolism in plants is shared between mitochondria and peroxisomes. The aim of this project is to elucidate the signaling and regulatory mechanisms that allocate leucine to the mitochondrial versus the peroxisomal catabolic pathways, and to determine how these catabolic pathways are networked with other metabolic processes. To do this, three specific hypotheses will be tested: Hypothesis 1: A block in mitochondrial leucine catabolism is compensated by global shifts in patterns of gene expression. Hypothesis 2: MCCase is the point of integration of leucine catabolism and isoprenoid metabolism. Hypothesis 3: Mitochondrial leucine catabolism is regulated by the metabolic status of the organism in part via changes in MCCase gene transcription. Plants take in simple molecules such as carbon dioxide, and water. Using energy from the sun, these are converted to complex compounds such as starch, proteins, fibers, oils and pharmaceuticals. In addition, these complex compounds are constantly broken down to provide energy for growth as well as to provide the new compounds needed by each plant cell to respond to an ever-changing environment. The net accumulation of useful biomolecules by the plant is thus dependent on the balance between two processes. The long-term goal of this research is to exploit the synergy inherent in a combined genetic and biochemical approach that will ultimately reveal how plants maintain such a balance.