Inhibition of proteasome activity by selected amino acids.
Cellular protein homeostasis is a balance between synthesis and degradation. Protein degradation is regulated by hormones (eg, insulin) and nutrients (eg, amino acids). Certain amino acids are capable of decreasing cellular protein degradation, with evidence that this is mediated through altered lysosomal function. However, proteasomes, the major cytosolic protein degrading machinery, are being shown to play a central role in the control of protein turnover in the cell. In this study we show that the amino acids, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, lysine, and arginine are capable of inhibiting the chymotrypsin-like activity of the proteasome in a dose-dependent manner. Leucine, tyrosine, and phenylalanine have a substantial effect at normal serum concentrations. The effect was greater in a proteasome preparation derived from muscle compared to a similar preparation from liver. On the assumption that amino acid-induced alterations in cellular protein degradation reflect the inhibitory changes in proteasomal activity shown here, we may conclude that amino acid control of cellular protein degradation is mediated, at least in part, through proteasomes.
Hamel
Frederick G
FG
Research Service, Department of Veterans Affairs Medical Center, Omaha, NE 68105, USA.
Upward
Jennifer L
JL
Siford
Gerri L
GL
Duckworth
William C
WC
D000596:Amino Acids / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007532:Isoleucine / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008239:Lysine / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000648:ultrastructure; D010649:Phenylalanine / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000494:pharmacology; D014443:Tyrosine / Q000494:pharmacology
D000596:Amino Acids; D004791:Enzyme Inhibitors; D007328:Insulin; D009097:Multienzyme Complexes; D007532:Isoleucine; D014443:Tyrosine; D010649:Phenylalanine; D014364:Tryptophan; D001120:Arginine; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D007930:Leucine; D008239:Lysine