A second Warburg-like effect in cancer metabolism: The metabolic shift of glutamine-derived nitrogen: A shift in glutamine-derived nitrogen metabolism from glutaminolysis to de novo nucleotide biosynthesis contributes to malignant evolution of cancer

Manabu Kodama, Keiichi I. Nakayama

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Article number2000169
JournalBioEssays
Volume42
Issue number12
DOIs
Publication statusPublished - Dec 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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