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. (9th November 2020)

• Record Type: Journal Article
• Authors: Kodama, Manabu; Nakayama, Keiichi I.
• Is Part Of: BioEssays. Volume 42:Number 12(2020:Dec.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-09
• Subjects: de novo nucleotide biosynthesis -- glutamine metabolism -- glutaminolysis -- meta‐analysis -- small cell lung cancer; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202000169
• Languages: English
• ISSNs: 0265-9247

Abstract

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. Abstract : In the premalignant state, carbons of glucose and glutamine are completely oxidized in the TCA cycle. In contrast, in malignant cancer, glucose metabolism is significantly shifted (the Warburg effect) and glutamine metabolism shifts from glutaminolysis to the de novo nucleotide biogenesis pathway (the "SECOND" Warburg effect).