Chapter 8 - Glutamine metabolism in prostate cancer

Abstract

Cancer cells have very high nutrient and energy requirements in order to synthesize a whole new cell. The most evident of these requirements is glucose, situated just on the visible part of the metabolic iceberg. However, under the water, an important part of the hidden iceberg is the need for nitrogen and nitrogen compounds. These compounds are used for (1) synthesis of nonessential amino acids as building blocks for proteins, (2) part of nitrogen bases, (3) production of molecules that intervene in the detoxification of reactive oxygen species, and (4) an important energy source. The cancer cell's metabolic switch includes the ability to use glutamine as an important alternative energy source to feed the Krebs cycle. Glutamine is the most abundant amino acid in the human body. It is a nonessential amino acid that can be synthesized in mammalian cells. However, certain tumors develop a high need for glutamine to the point that for all practical purposes, glutamine becomes an essential amino acid with insufficient intracellular synthesis to satisfy the high need. In these cases, the cell is said to be glutamine-addicted and strongly dependent of extracellular uptake. Amino acids in general and leucine in combination with glutamine also have a role in the signaling of mTOR.