Glutamine breakdown in rapidly dividing cells: waste or investment?

Tumours, and in general rapidly dividing cells, behave as dissipative devices that apparently waste glutamine, since its consumption seems to exceed both energetic and nitrogen needs. Although not conclusive, there is compelling evidence suggesting that the consumption of such large amounts of glutamine is essential to sustain high rates of cellular proliferation. Herein, I first review the experimental evidence linking proliferation with high rates of glutamine breakdown. Then, the current knowledge on the proteins and activities involved in this high glutamine consumption will be summarized. Finally, the significance of the apparent waste of glutamine will be discussed on bioenergetic grounds. The discussion leads to the hypothesis that glutamine breakdown might energize some endergonic processes, as well as accelerating other exergonic processes related to cellular proliferation. BioEssays 26:778–785, 2004. © 2004 Wiley Periodicals, Inc.