Muscle glutamine concentration and protein turnover in vivo in malnutrition and in endotoxemia

Abstract

A comparison of the changes in the concentration of glutamine [Gln] in skeletal muscle in a variety of catabolic states with the attendant changes in rates of protein synthesis and degradation indicates a number of substantial correlations which provide insight into both the way in which [Gln] is regulated in muscle and possible regulatory influences of [Gln] on protein balance. There is a striking direct correlation between [Gln] and the rate of protein synthesis in the whole data set. Further examination of this relationship in protein deficiency shows that the changes in [Gln] correlate mainly with the reductions in ribosomal concentration (RNA/protein) and with the decrease in the rate of protein degradation. Because the fall in [Gln] in protein deficiency is also correlated with the decrease in free T 3 concentrations, it is suggested that in this case the correlations of [Gln] with rates of protein turnover may be incidental, reflecting thyroidal influences on both protein turnover and glutamine transport. In contrast, in endotoxemia the changes in [Gln] were highly correlated with the ribosomal activity, k RNA, and in this case [Gln] was inversely correlated with the rate of protein degradation. Similar correlated changes occur in starvation and in response to glucocorticoids, and it is suggested that the reductions in [Gln] in endotoxemia could be causally related to the development of insulin resistance and the inhibition of the translational phase of protein synthesis which occurs in these circumstances. The mechanism of the reduction in [Gln] and any linked inhibition of protein synthesis is unknown, but it is shown to be independent of prostaglandin production. The sensitivity of the [Gln]-protein synthesis link, in terms of the slope of the correlation, decreases with both protein deficiency and with vitamin E deficiency. Indeed, in rats fed very-low-protein, vitamin-E-deficient diets, although [Gln] levels decrease in response to the endotoxin, the protein-catabolic response is blocked because protein synthesis does not change. The relationships between [Gln] and rates of protein turnover are unique, ie, not observed with any other amino acid. The results provide further evidence that the characteristics of the regulation of the muscle glutamine pool enable it to serve an important homeostatic role in the organism, acting as a labile store of nitrogen which is mobilized in times of stress, and provide some support for the suggestion that repletion of muscle glutamine in catabolic states could reduce muscle wasting.