Inhibition of proteasome activity by selected amino acids

Frederick G Hamel, Jennifer L. Upward, Gerri L. Siford, William C. Duckworth

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)810-814
Number of pages5
JournalMetabolism: Clinical and Experimental
Volume52
Issue number7
DOIs
StatePublished - Jul 1 2003

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Proteasome Endopeptidase Complex
Proteolysis
Amino Acids
Phenylalanine
Leucine
Tyrosine
Proteins
Isoleucine
Chymotrypsin
Tryptophan
Lysine
Arginine
Homeostasis
Hormones
Insulin
Food
Muscles
Liver
Serum

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Inhibition of proteasome activity by selected amino acids. / Hamel, Frederick G; Upward, Jennifer L.; Siford, Gerri L.; Duckworth, William C.

In: Metabolism: Clinical and Experimental, Vol. 52, No. 7, 01.07.2003, p. 810-814.

Research output: Contribution to journalArticle

Hamel, Frederick G ; Upward, Jennifer L. ; Siford, Gerri L. ; Duckworth, William C. / Inhibition of proteasome activity by selected amino acids. In: Metabolism: Clinical and Experimental. 2003 ; Vol. 52, No. 7. pp. 810-814.
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