Muscle glutamine concentration and protein turnover in vivo in malnutrition and in endotoxemia.
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 T3 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, kRNA, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Millward
D J
DJ
Department of Human Nutrition, London School of Hygiene and Tropical Medicine, England.
Jepson
M M
MM
Omer
A
A
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D004731:Endotoxins / Q000097:blood* / Q000494:pharmacology; D004926:Escherichia coli; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D009132:Muscles / Q000378:metabolism*; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D013217:Starvation / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood; D014811:Vitamin E Deficiency / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D004731:Endotoxins; D009124:Muscle Proteins; D014284:Triiodothyronine; D005973:Glutamine; D012964:Sodium