Regulation and Metabolic Networking of Leucine Catabolism

生物体保持吸收和吸收之间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，以应对各种各样的发育和环境信号。 对于静止的生物体，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（MCCase）代谢功能的研究表明，植物亮氨酸羧化酶与其它代谢和生理过程是网络化的。 因此，植物亮氨酸催化剂的研究可能会提供新的见解，生物体网络代谢，以实现复杂的网状过程的几个层次的调节。 该项目的重点是在拟南芥中的亮氨酸catalysts的调节，作为一个例子，如何复杂的相互关联的代谢途径控制，以实现生物分子的净相互转换。 已经表明，植物通过需要酶MCCase的线粒体途径分解代谢亮氨酸。 此外，MCC酶缺陷遗传原种的特征表明，植物中的亮氨酸催化酶在线粒体和过氧化物酶体之间共享。该项目的目的是阐明将亮氨酸分配给线粒体与过氧化物酶体分解代谢途径的信号传导和调节机制，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，将测试三个具体的假设：假设1：线粒体亮氨酸催化剂的阻断通过基因表达模式的全局变化来补偿。 假设2：MCCase是亮氨酸催化剂和类异戊二烯代谢的整合点。 假设3：线粒体亮氨酸催化酶部分通过MCCase基因转录的变化受生物体代谢状态的调节。 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，这些被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，并为每个植物细胞提供所需的新化合物，以应对不断变化的环境。 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物化学相结合的方法中固有的协同作用，最终揭示植物如何保持这种平衡。

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.