In-Depth Understanding of the Metabolic Regulation and Coordination of the Metabolism in Cell Systems

Date: 2014.11.19/Nov. 19，下午/pm,13:30

Location: 2-116, Life Sciences Building

Reporter: Prof. Kazuyuki Shimizu

Kyushu Institute of Technology & Institute of Advanced Biosciences, Keio university, Japan

报告摘要/Abstract：

Living organisms have sophisticated but well organized regulation system in response to the change in growth environment. Metabolism is the core for energy generation (catabolism) and cell synthesis (anabolism). Recent investigation on the metabolism is widespread ranging from bacteria, fungi, photosynthetic organisms, to human as well as cancer cell. Deep understanding on the metabolic regulation mechanism is essential for manipulating and redesigning the metabolism, and it is critical to understand the basic principles which govern the cell metabolism. Such principles may be in common to various organisms, while some are the specific to the organism of concern.

In general, fast action is made by the enzyme level regulation such as the feed-forward activation of pyruvate kinase (Pyk) by fructose 1,6-bisphosphate (FBP), a motif that enables a high level of the upstream metabolite to lower the level of the downstream metabolite. Such enzyme level regulation mechanism is well conserved in many organisms. The slow action is made by the transcriptional regulation, where this mechanism depends on the organism. The cell system achieves the coupling between recognition and adjustment through transcription factors (TFs), whose activities respond to the culture environment, and regulate the expression of the associated genes. The coherent behavior of the overall system is not established by a common transcriptional master regulator, but emerges from the molecular interactions within the network system. After glucose depletion, FBP concentration decreases, and Ppc and Pyk activities decrease in turn by the allosteric regulation, and PEP consumption is almost completely turned off. These make PEP concentration to be increased, and this buildup of PEP is kept high during certain period, and this serves to quickly uptake the glucose by PTS if it becomes available again. Among intracellular metabolites, α-keto acid such as αKG turns to be a mater regulator for the co-ordination of catabolic and anabolic regulations. Moreover, there is a hierarchy for the uptake of various carbon sources, where this may be the strategy for the cells to survive in the living environment.