10月主題介紹 – 生物的新陳代謝 Metabolism

　　新陳代謝 (Metabolism) 是生物體內最古老的機制之一。從原核生物到真核生物，細胞都需要能量供給，更需要合成生物體內必須的材料。為了維持生命系統的穩定，生物演化出複雜且華麗的生化網路；細胞膜作為生命的界線，細胞內部必須耗能以避免系統朝最大亂度發展，而生化反應就是其中的魔法所在，是構築生命的骨架。也因此生化反應成為所有生物功能的基礎，幾乎一切都與新陳代謝有關，從細胞到個體層級皆是如此。

　　隨著各種體學的發展，科學家開始發現新陳代謝於各種系統功能中的重要性，原本複雜難解的生物化學，成為各個學門新興的熱門話題。這個月，我們將由小至大、從古至今，以不同角度探討新陳代謝的迷人機制。從為人所知的呼吸作用的演化開始說起，究竟在蛋白質被製造之前，生命共同的始祖是如何進行生化反應 ^[1]？不僅如此，經過悠遠的演化，人體中的恆定 (homeostasis)、免疫系統 (immune system) ^{[2, 3]}、幹細胞分化 (stem cell proliferation) ^[4] 都與新陳代謝的程序有密切的關係。代謝產物可以透過影響表觀遺傳 (epigenetics)、蛋白質修飾、能量代謝與直接參與化學反應而影響細胞的功能呈現。不僅如此，當新陳代謝產生錯誤，疾病便會隨之產生，癌症 (cancer) ^{[2, 5-7]}、阿茲海默症 (Alzheimer’s disease) ^[8]、糖尿病 (diabetes) ^[9] 與老化 (aging) ^[10] 都與新陳代謝緊密相關，從細胞到系統層級皆是如此。究竟代謝反應是如何與細胞或個體間的系統合作運作的呢？

　　這個月，我們將專注於探討新陳代謝的多元面貌，希望帶領讀者們體驗到與以往不同的新陳代謝與生化反應！

參考文獻：

1. Muchowska, K. B., Varma, S. J., & Moran, J. (2019). Synthesis and breakdown of universal metabolic precursors promoted by iron. Nature, 569(7754), 104. https://doi.org/10.1038/s41586-019-1151-1 
2. Bengsch, B., Johnson, A. L., Kurachi, M., Odorizzi, P. M., Pauken, K. E., Attanasio, J., . . . Delgoffe, G. M. (2016). Bioenergetic insufficiencies due to metabolic alterations regulated by the inhibitory receptor PD-1 are an early driver of CD8+ T cell exhaustion. Immunity, 45(2), 358-373. https://doi.org/10.1016/j.immuni.2016.07.008
3. Galván-Peña, S., Carroll, R. G., Newman, C., Hinchy, E. C., Palsson-McDermott, E., Robinson, E. K., . . . Haneklaus, M. (2019). Malonylation of GAPDH is an inflammatory signal in macrophages. Nature communications, 10(1), 338. https://doi.org/10.1038/s41467-018-08187-6 
4. Varum, S., Baggiolini, A., Zurkirchen, L., Atak, Z. K., Cantù, C., Marzorati, E., . . . Tuncer, E. (2019). Yin Yang 1 Orchestrates a Metabolic Program Required for Both Neural Crest Development and Melanoma Formation. Cell Stem Cell, 24(4), 637-653. e639. https://doi.org/10.1016/j.stem.2019.03.011
5. Halbrook, C. J., Pontious, C., Kovalenko, I., Lapienyte, L., Dreyer, S., Lee, H.-J., . . . Sajjakulnukit, P. (2019). Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer. Cell metabolism, 29(6), 1390-1399. e1396. https://doi.org/10.1016/j.cmet.2019.02.001
6. Wang, H.-J., Hsieh, Y.-J., Cheng, W.-C., Lin, C.-P., Lin, Y.-s., Yang, S.-F., . . . Kung, H.-J. (2014). JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α–mediated glucose metabolism. Proceedings of the National Academy of Sciences, 111(1), 279-284. https://doi.org/10.1073/pnas.1311249111
7. Angione, C. (2017). Integrating splice-isoform expression into genome-scale models characterizes breast cancer metabolism. Bioinformatics, 34(3), 494-501. https://doi.org/10.1093/bioinformatics/btx562
8. Baik, S. H., Kang, S., Lee, W., Choi, H., Chung, S., Kim, J.-I., & Mook-Jung, I. (2019). A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer’s Disease. Cell metabolism. https://doi.org/10.1016/j.cmet.2019.06.005
9. Engelman, J. A., Luo, J., & Cantley, L. C. (2006). The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nature Reviews Genetics, 7(8), 606. https://doi.org/10.1038/nrg1879 
10. Stekovic, S., Hofer, S. J., Tripolt, N., Aon, M. A., Royer, P., Pein, L., . . . Url, J. (2019). Alternate day fasting improves physiological and molecular markers of aging in healthy, non-obese humans. Cell metabolism. https://doi.org/10.1016/j.cmet.2019.07.016

撰文｜蔡宗霖
審稿｜吳冠廷