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However, how to find targets to effectively block the hypoxia-associated metabolic pathways remains unclear. Here, we developed a tool to conveniently calculate electrons dissipated in metabolic transformations. Based on the law of conservation of electrons in chemical reactions, we further built up an electron balance model for central carbon metabolism, and it can accurately outline metabolic plasticity under hypoxia. Our model specifies that glutamine metabolism reprogrammed for biosynthesis of lipid and\/or proline actually acts as the alternative electron bin to enable electron transfer in proliferating cells under hypoxia. Inhibition of both proline biosynthesis and lipogenesis can synergistically suppress cancer cell growth under hypoxia and in vivo tumor onset. Therefore, our model helps to reveal combinations of potential targets to inhibit tumor growth by blocking hypoxia-rewired metabolism and provides a useful tool for future studies on cancer metabolism.<\/jats:p>","DOI":"10.1084\/jem.20191226","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T09:59:40Z","timestamp":1579600780000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth"],"prefix":"10.1084","volume":"217","author":[{"given":"Miao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People\u2019s Republic of China 1"},{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 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