Brugge lab uncovers important role for transaminases in proliferating cells

Graphics of Proliferation and Quiescence

In order to proliferate, cells must reproduce their biomass by acquiring nutrients from their environment and using them to synthesize macromolecules. Using a 3D tissue culture model combined with quantitative metabolomics and proteomics, members of the Brugge and Gygi labs have identified a mechanism by which proliferating cells use glutamate to support the biosynthesis of other non-essential amino acids (Coloff et al, Cell Metabolism, 2016). In proliferating cells, transaminases that make use of both the carbon and nitrogen from glutamate are utilized to generate amino acids and to fuel the TCA cycle. When cells exit the cell cycle, they reduce transaminase expression and induce an alternative enzyme, glutamate dehydrogenase, which no longer makes use of glutamate-derived nitrogen, thereby reducing amino acid biosynthesis. Importantly, this pathway appears to be used by rapidly proliferating cells from a variety of tissues and organisms, as well as by most rapidly proliferating tumor cells. This work highlights the importance of achieving a detailed understanding of the mechanisms by which cells utilize nutrients if we hope to target the aberrant metabolism observed in cancer cells as cancer therapy.