Linkage between postabsorptive amino acid release and glutamate uptake in skeletal muscle tissue of healthy young subjects, cancer patients, and the elderly.
Several diseases of varying etiology that are commonly associated with the loss of skeletal muscle mass were found to be associated with a decrease in muscular glutamate and glutathione levels and in glutamate uptake in the postabsorptive state. In view of the Na+ dependency and insulin responsiveness of glutamate transport we studied the postabsorptive glutamate exchange in more detail. Our study demonstrates a linkage between glutamate uptake and the export of other amino acids, suggesting that protein catabolism and the resulting coexport of amino acids plus Na+ substitute for insulin as a driving force for the Na+ gradient in the postabsorptive state. The regression function of the correlation between relative glutamate exchange and cumulative amino acid exchange in cancer patients was lower than that in non-tumor-bearing subjects, suggesting that cancer patients must release more amino acids to achieve the same glutamate uptake. In addition, cancer patients had a lower average cumulative amino acid exchange rate than non-tumor-bearing subjects, suggesting that the abnormally low relative glutamate exchange capacity of cancer patients results mainly from inadequate postabsorptive protein catabolism in the skeletal muscle tissue. Both cancer patients and non-tumor-bearing elderly subjects had higher arterial glutamate levels and alanine release than young subjects, indicative of a substantial glycolytic activity in the skeletal muscle. However, elderly non-tumor-bearing subjects showed, in contrast to cancer patients, in the postabsorptive state a stronger cumulative amino acid release and postabsorptive glutamate uptake than healthy young subjects. These changes are discussed in view of the age-related loss of skeletal muscle mass.
Holm
E
E
Department of Pathophysiology, Medical Clinic I Mannheim, University of Heidelberg, Germany.
Hack
V
V
Tokus
M
M
Breitkreutz
R
R
Babylon
A
A
Dröge
W
W
D000328:Adult; D000368:Aged; D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D019518:Postprandial Period; D012016:Reference Values
D000596:Amino Acids; D018698:Glutamic Acid; D000409:Alanine