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Both liver and muscle can produce and release glutamine into the bloodstream, but muscle may be quantitatively the most important tissue. Since the cells of the intestine have a large capacity to utilize glutamine, most of the glutamine that enters the body via the diet is utilized by the intestine. Hence glutamine production and release by muscle become of considerable physiological and immunological importance.

The systematic study of glutamine flux in skeletal muscle, using the principles of metabolic-control logic, has highlighted two areas of potential misunderstanding in the literature. These relate to the processes of glutamine synthesis in muscle and the processes of glutamine uptake and release across the muscle membrane. It should be emphasized that glutamine synthesis, uptake and release by muscle are three distinct processes. Evidence has been obtained that the process of glutamine release from skeletal muscle may be the limiting step - indeed may be the flux-generating step - for maintenance of the plasma glutamine level and hence its uptake by other cells (e.g., immune cells).