Low postabsorptive net protein degradation in male cancer patients: lack of sensitivity to regulatory amino acids?
Autophagic (lysosomal) and proteasomic protein degradation are important regulatory mechanisms in the homeostasis of muscle mass, that may be profoundly disturbed in cancer and other wasting syndromes. Due to the inhibiting effect of amino acids and insulin, net proteolysis is restricted to the fasted state, and in autophagy certain amino acids have been identified as 'regulatory' in the rat, including leucine, tyrosine, phenylalanine, methionine, and histidine (i.e. LYFMH). The present cross-sectional study assessed postabsorptive net protein catabolism in male cancer patients as well as in healthy male volunteers, to analyse its relation to such 'regulatory amino acids'. Postabsorptive amino acid exchange rates across the leg were determined in patients with gastrointestinal cancer (GIC, n=47) or renal cell carcinoma (RCC, n=15), age-matched (n=33), and young male control subjects (n=42). Both groups of cancer patients revealed a significantly lower postabsorptive net protein catabolism than control subjects. Furthermore, in the control subjects, the postabsorptive net protein catabolism was found to be inversely and significantly correlated with the arterial concentrations of the 8 amino acids YSHMFGI and L which include 5 of the 'regulatory amino acids'. Cancer patients, in contrast, revealed no such significant correlations. These results may indicate i) that postabsorptive net protein catabolism in skeletal muscle of healthy subjects may be sensitive to amino acids which reportedly regulate autophagy and ii) that such amino acid-sensitive mechanism of protein catabolism may be disturbed in cancer patients.
Holm
Eggert
E
Department of Pathophysiology, Medical Clinic 1 Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.
Hildebrandt
Wulf
W
Kinscherf
Ralf
R
Dröge
Wulf
W
D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D011506:Proteins / Q000378:metabolism*
D000596:Amino Acids; D011506:Proteins; D046988:Proteasome Endopeptidase Complex