Glutamine and glutamate—their central role in cell metabolism and function

Glucose is widely accepted as the primary nutrient for maintenance and promotion of cell function. However, we propose that the 5-carbon amino acids, glutamine and glutamate, should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine are many and include: substrate for protein synthesis, anabolic precursor for muscle growth, acid-base balance in the kidney, substrate for ureogenesis in the liver, substrate for hepatic and renal gluconeogenesis, an oxidative fuel for intestine and cells of the immune system, inter-organ nitrogen transport, precursor for neurotransmitter synthesis, precursor for nucleotide and nucleic acid synthesis and precursor for glutathione production. Many of these functions are connected to the formation of glutamate from glutamine. We propose that the unique properties regarding concentration and routes of metabolism of these amino acids allow them to be used for a diverse array of processes related to the specialized function of each of the glutamine utilizing cells. In this review we highlight the specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells and in each case relate key aspects of metabolism to cell function.