QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kadowaki, M. Articles by Kanazawa, T. Search for Related Content PubMed PubMed Citation Articles by Kadowaki, M. Articles by Kanazawa, T.

---

Supplement: 2nd Amino Acid Workshop

Amino Acids as Regulators of Proteolysis^1,2

Department of Applied Biological Chemistry, Faculty of Agriculture, Niigata University, Ikarashi, Niigata 950-2181, Japan

³ To whom correspondence should be addressed. E-mail: kadowaki{at}agr.niigata-u.ac.jp.

Proteolysis, as well as protein synthesis, is a major process that contributes to the body protein turnover. Despite the huge variety of proteases in the body, there are very few proteolytic systems contributing to the complete hydrolysis of proteins to amino acids. The autophagic-lysosomal pathway is responsible for bulk proteolysis, whereas the ubiquitin-proteasome pathway plays a significant role in the fine control of the degradation of specific proteins. Both systems can produce free amino acids as a final product, but only the autophagy system is physiologically controlled by plasma amino acids. Recently, the study of amino acids as regulators of macromolecular turnover has been focused on for their signal transduction mechanism. In autophagic proteolysis, several amino acids have a direct regulatory potential: Leu, Gln, Tyr, Phe, Pro, Met, Trp and His in the liver, and Leu in the skeletal muscle. These amino acids are recognized at the plasma membrane, indicating the possible existence of an amino acid receptor/sensor for their recognition and subsequent intracellular signaling. Another line of evidence has emerged that protein kinase cascades such as mTOR, Erk, eIF2 etc. may be involved in the regulation of autophagy, and that amino acids, in combination with insulin, may exert their effects through these pathways. From the viewpoint of amino acid safety, the contribution of proteolysis to possible adverse effects caused by excessive amino acid intake is not clear. At present, there is one report that excess glutamine at 10-fold the plasma level has an abnormal inhibitory effect on hepatic proteolysis, due to a lysosomotropic toxicity of ammonia derived from glutamine degradation. Whether this may lead to an adverse effect in humans remains to be clarified.

KEY WORDS: • autophagy • proteasome • amino acid signaling • mTOR • glutamine

This article has been cited by other articles:

				R. A. Nixon Autophagy, amyloidogenesis and Alzheimer disease J. Cell Sci., December 1, 2007; 120(23): 4081 - 4091. [Abstract] [Full Text] [PDF]

				M. Katoh, G. Chen, E. Roberge, G. Shaulsky, and A. Kuspa Developmental Commitment in Dictyostelium discoideum Eukaryot. Cell, November 1, 2007; 6(11): 2038 - 2045. [Abstract] [Full Text] [PDF]

				J. Talvas, A. Obled, P. Fafournoux, and S. Mordier Regulation of Protein Synthesis by Leucine Starvation Involves Distinct Mechanisms in Mouse C2C12 Myoblasts and Myotubes J. Nutr., June 1, 2006; 136(6): 1466 - 1471. [Abstract] [Full Text] [PDF]

				W. H. Yu, A. M. Cuervo, A. Kumar, C. M. Peterhoff, S. D. Schmidt, J.-H. Lee, P. S. Mohan, M. Mercken, M. R. Farmery, L. O. Tjernberg, et al. Macroautophagy--a novel {beta}-amyloid peptide-generating pathway activated in Alzheimer's disease J. Cell Biol., October 10, 2005; 171(1): 87 - 98. [Abstract] [Full Text] [PDF]

				P. J. Garlick The Role of Leucine in the Regulation of Protein Metabolism J. Nutr., June 1, 2005; 135(6): 1553S - 1556S. [Abstract] [Full Text] [PDF]

				I. Tanida, Y.-s. Sou, J. Ezaki, N. Minematsu-Ikeguchi, T. Ueno, and E. Kominami HsAtg4B/HsApg4B/Autophagin-1 Cleaves the Carboxyl Termini of Three Human Atg8 Homologues and Delipidates Microtubule-associated Protein Light Chain 3- and GABAA Receptor-associated Protein-Phospholipid Conjugates J. Biol. Chem., August 27, 2004; 279(35): 36268 - 36276. [Abstract] [Full Text] [PDF]

				D. W. Gietzen, C. M. Ross, S. Hao, and J. W. Sharp Phosphorylation of eIF2{alpha} Is Involved in the Signaling of Indispensable Amino Acid Deficiency in the Anterior Piriform Cortex of the Brain in Rats J. Nutr., April 1, 2004; 134(4): 717 - 723. [Abstract] [Full Text] [PDF]

				X. Wang and S. R. Price Differential regulation of branched-chain {alpha}-ketoacid dehydrogenase kinase expression by glucocorticoids and acidification in LLC-PK1-GR101 cells Am J Physiol Renal Physiol, March 1, 2004; 286(3): F504 - F508. [Abstract] [Full Text]

				P. Razeghi, S. Sharma, J. Ying, Y.-P. Li, S. Stepkowski, M. B. Reid, and H. Taegtmeyer Atrophic Remodeling of the Heart In Vivo Simultaneously Activates Pathways of Protein Synthesis and Degradation Circulation, November 18, 2003; 108(20): 2536 - 2541. [Abstract] [Full Text] [PDF]