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癌症中的丝氨酸和甘氨酸代谢

Serine and glycine metabolism in cancer.

作者信息

Amelio Ivano, Cutruzzolá Francesca, Antonov Alexey, Agostini Massimiliano, Melino Gerry

机构信息

Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK.

Department of Biochemical Sciences, University of Rome "Sapienza", 00185 Rome, Italy.

出版信息

Trends Biochem Sci. 2014 Apr;39(4):191-8. doi: 10.1016/j.tibs.2014.02.004. Epub 2014 Mar 20.

Abstract

Serine and glycine are biosynthetically linked, and together provide the essential precursors for the synthesis of proteins, nucleic acids, and lipids that are crucial to cancer cell growth. Moreover, serine/glycine biosynthesis also affects cellular antioxidative capacity, thus supporting tumour homeostasis. A crucial contribution of serine/glycine to cellular metabolism is through the glycine cleavage system, which refuels one-carbon metabolism; a complex cyclic metabolic network based on chemical reactions of folate compounds. The importance of serine/glycine metabolism is further highlighted by genetic and functional evidence indicating that hyperactivation of the serine/glycine biosynthetic pathway drives oncogenesis. Recent developments in our understanding of these pathways provide novel translational opportunities for drug development, dietary intervention, and biomarker identification of human cancers.

摘要

丝氨酸和甘氨酸在生物合成上相互关联,共同为蛋白质、核酸和脂质的合成提供必需的前体物质,而这些物质对癌细胞的生长至关重要。此外,丝氨酸/甘氨酸的生物合成还会影响细胞的抗氧化能力,从而维持肿瘤内环境稳定。丝氨酸/甘氨酸对细胞代谢的一个关键贡献是通过甘氨酸裂解系统实现的,该系统为一碳代谢补充燃料;一碳代谢是一个基于叶酸化合物化学反应的复杂循环代谢网络。遗传和功能证据表明丝氨酸/甘氨酸生物合成途径的过度激活会驱动肿瘤发生,这进一步凸显了丝氨酸/甘氨酸代谢的重要性。我们对这些途径理解的最新进展为人类癌症的药物开发、饮食干预和生物标志物识别提供了新的转化机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79a8/3989988/cf660d8c72ce/gr1.jpg

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