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Fenton reactions drive nucleotide and ATP syntheses in cancer
Huiyan Sun 1,2 , Chi Zhang 2 , Sha Cao 2 , Tao Sheng 2 , Ning Dong 2,4 , and Ying Xu 1,2,3,*
1 College of Computer Science and Technology, Jilin University, Changchun, China
2 Computational Systems Biology Lab, Department of Biochemistry and Molecular Biology and Institute of Bioinformatics, University of Georgia, GA, USA
3 School of Public Health, Jilin University, Changchun, China
4 The First Hospital of Jilin University, Changchun, China
*Correspondence to:Ying Xu, E-mail: xyn@uga.edu
J Mol Cell Biol, Volume 10, Issue 5, October 2018, Pages 448-459  https://doi.org/10.1093/jmcb/mjy039
Keyword: cancer driver, Fenton reaction, gene-expression data, intracellular pH, Warburg effect
We present a computational study of tissue transcriptomic data of 14 cancer types to address: what may drive cancer cell division? Our analyses point to that persistent disruption of the intracellular pH by Fenton reactions may be at the root of cancer development. Specifically, we have statistically demonstrated that Fenton reactions take place in cancer cytosol and mitochondria across all the 14 cancer types, based on cancer tissue gene-expression data integrated via the Michaelis–Menten equation. In addition, we have shown that (i) Fenton reactions in cytosol of the disease cells will continuously increase their pH, to which the cells respond by generating net protons to keep the pH stable through a combination of synthesizing glycolytic ATPs and consuming them by nucleotide syntheses, which may drive cell division to rid of the continuously synthesized nucleotides; and (ii) Fenton reactions in mitochondria give rise to novel ways for ATP synthesis with electrons ultimately coming from H2O2, largely originated from immune cells. A model is developed to link these to cancer development, where some mutations may be selected to facilitate cell division at rates dictated by Fenton reactions.