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A second Warburg‐like effect in cancer metabolism: The metabolic shift of glutamine‐derived nitrogen
Author(s) -
Kodama Manabu,
Nakayama Keiichi I.
Publication year - 2020
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.202000169
Subject(s) - warburg effect , glutaminolysis , glutamine , metabolism , cancer cell , cancer , biochemistry , metabolic pathway , biology , carbohydrate metabolism , chemistry , cancer research , glycolysis , amino acid , genetics
Abstract Carbon and nitrogen are essential elements for life. Glucose as a carbon source and glutamine as a nitrogen source are important nutrients for cell proliferation. About 100 years ago, it was discovered that cancer cells that have acquired unlimited proliferative capacity and undergone malignant evolution in their host manifest a cancer‐specific remodeling of glucose metabolism (the Warburg effect). Only recently, however, was it shown that the metabolism of glutamine‐derived nitrogen is substantially shifted from glutaminolysis to nucleotide biosynthesis during malignant progression of cancer—which might be referred to as a “second” Warburg effect. In this review, address the mechanism and relevance of this metabolic shift of glutamine‐derived nitrogen in human cancer. We also examine the clinical potential of anticancer therapies that modulate the metabolic pathways of glutamine‐derived nitrogen. This shift may be as important as the shift in carbon metabolism, which has long been known as the Warburg effect.