Role of membrane transport in the regulation of skeletal muscle glutamine turnover.
This paper reviews present understanding of the role played by the sarcolemmal glutamine transporter, system N(m), in control of intramuscular glutamine concentration. Glutamine transport in skeletal muscle is a saturable, stereospecific, Na dependent and insulin sensitive process. The activity of system N(m) is subject to modification during muscle denervation, diabetes and exposure to bacterial products in a manner consistent with the observed negative glutamine balance exhibited by muscle during such circumstances. The modification in transporter activity appears to be dependent on factors influencing the distribution of Na across the sarcolemma, the resting membrane potential and the active carrier population in the sarcolemma (possibly through up or down regulation of the number of transporter molecules). Derangements in net membrane glutamine transport during pathophysiological conditions may help, partly, to account for the loss in muscle glutamine which in turn may influence control of protein and carbohydrate metabolism in muscle. The free intramuscular glutamine concentration appears to act as a positive signal in the control of muscle protein turnover and glycogen synthesis, a finding that may have important therapeutic implications for limiting muscle wasting. The kinetic properties of the glutamine transporter and the dipeptidase activity in the muscle vascular bed allow the intramuscular glutamine pool to be repleted following administration of glutamine dipeptides (such as Ala-Gln) with the result that a net anabolic shift in protein balance and an amelioration in muscle glutamine efflux takes place.
Hundal
H S
HS
Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, Scotland, UK.