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Program in Cell and Molecular Biosciences, Department of Animal and Dairy Sciences, Auburn University, Auburn, AL 36849-5415
3To whom correspondence should be addressed. E-mail: wbergen{at}acesag.auburn.edu
For nearly a century there has been a clear recognition of a
relationship between dietary amino acid supply and lean tissue growth
and maintenance. Early workers recognized that growth of young animals
was related to the quantity as well as source of protein in the diet.
From such observations emerged the concepts of indispensable and
dispensable amino acids and protein quality (1
). It was
ascertained that dispensable amino acids are synthesized in animals
while indispensable amino acids had to be provided in the diet. Protein
sources that resulted in poor growth were classified as being of low
quality, while conversely, protein sources which resulted in good or
excellent growth were deemed of good or high quality. Moreover, it was
recognized that the efficiency or extent of assimilation of amino acid
nitrogen into new tissues and lean growth were somehow intimately
linked to the process of protein deposition in tissues. For decades
work in protein nutrition and metabolism centered on determination of
nutritional quality of dietary protein sources, determination of
indispensable amino acid requirements, the role of unfavorable amino
acid profiles (balance) and the effect of the limiting amino acid on
nitrogen balance and lean tissue growth.
First descriptions of a protein synthesis mechanism emerged in the
middle of the 20th century. Researchers recognized that the site of
protein synthesis in the cell is the ribosome and that the protein
synthesis mechanism involves soluble components, such as the so called
pH 5 enzymes, in the cell cytosol (2
). The general
framework of the protein synthesis mechanism or the translation
apparatus, including the roles of ribosomes, a template/message RNA and
s/tRNAs was described by the 1960s (2
). While final
descriptions of the structural and operational components of the
translation apparatus have not yet emerged, many aspects of protein
biosynthesis, including the role of ribosomes and ribosomal subunits,
ribosomal proteins, tRNA, formation of the ternary complex, role of
initiation, elongation and termination factors, have been documented
(3
, 4
). In addition, significant advances have been
reported in crystallization and structural analysis of ribosomes
(5
, 6
).
Professor Hamish N. Munro, in a presentation entitled "Role of amino
acid supply in regulating ribosome function" (7
),
demonstrated that the lack of dietary protein resulted in a rapid loss
of liver weight related to a decline in protein content and parallel
alterations in RNA and phospholipid content of this organ. Based on
these and other observations he proposed an integrative response
mechanism to amino acid supply by the liver, writing "the influx of
amino acids after a meal stimulates protein synthesis, reduces protein
breakdown and entrains more free ribosomes into polysomes, so that
fewer become degraded. When absorption of amino acids ceases, the
processes are reversed, so there is accelerated breakdown both of
protein and of RNA in the cell." (7
). These ideas were
extended in a joint symposium held by The Nutrition and Biochemistry
Societies (UK) on, "The Influence of Amino Acid Supply on
Polynucleotide and Protein Metabolism" (8
). What clearly
emerged at that time was the concept that cellular rRNA (ribosome)
content and function were modulated by the available amino acid supply.
This coupling of amino acid supply with tissue rRNA content, polysome
aggregation, and rate of translation is similar to the relationship
noted between growth rate, cellular rRNA content and amino acid supply
in stringent microorganisms (9
, 10
).
The last 3 decades have witnessed massive work on translation, ribosome
function and translational control (5
, 11
–14
). More
recently some amino acids have emerged as regulatory molecules in
translation in addition to their usual role as protein building blocks
(15
–17
). These concepts have broadened our understanding
of translation and have provided new insights into the
interrelationship between nutrition, the translation apparatus and
translational control. In addition, this emerging understanding has
resulted in new research on the interrelationships between the
translation system and nutritional factors such as amino acid supply
and energy sources. The symposium "Translational Control: A
Mechanistic Perspective" summarizes contemporary biochemistry and
molecular biology underlying structural and functional components of
the translation apparatus and protein biosynthesis.
Dr. Sonenberg presented a lecture on translational control, initiation and the role of target of rapamycin, Dr. Jakubowski focused on the editing function of tRNA ligases, Dr. Wower described the role and function of small RNPs in protein synthesis and Dr. Cunningham delineated genetic approaches to study structural and functional aspects of translation. In manuscript format, these discussions should be beneficial to both workers in various biomedicine fields and translation specialists.
 |
FOOTNOTES |
|---|
2 This work was supported in part by the Upchurch Fund for
Excellence.
|
LITERATURE CITED |
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 TOP LITERATURE CITED |
|---|
1. Harper, A. E. (1974) Basic concepts 1974 Improvement of Protein Nutriture National Academy of Sciences, Washington, D.C., pp 1–22. .
2. Korner, A. (1964) Protein biosynthesis in mammalian tissues. Munro, H. N. Allison, J. B. eds. Mammalian Protein Metabolism 1. Chapter 6:178-242 Academic Press New York and London .
3. Hill, W. E., Dahlberg, A., Garrett, R. A., Moore, P. B., Schlessinger, D & Warner, J. R. (1990) The Ribosome 1990 American Society for Microbiology. Washington D.C. .
4. Garrett, R. A., Douthwaite, S. R., Liljas, A., Matheson, A. T., Moore, P. B. & Noller, H. F. (2000) The Ribosome 2000 American Society for Microbiology. Washington D.C. .
5. Cate, J. H., Yusopov, M. M., Yusopova, G. Z., Earnest, T. N. & Noller, H. F. (1999) X-ray crystal structure of 70S ribosomal functional complexes. Science 285:2095-2104.
6. Lui, M. & Steitz, T. A. (2000) Structure of Escherichia coli ribosomal protein L25 complexed with a 5S rRNA fragment at 1.8-A resolution. Proc. Natl. Acad. Sci. 97:2023-2028.
7. Munro, H. N. (1968) Role of amino acid supply in regulating ribosome function. Federation Proc 27:1231-1237.[Medline]
8. The Nutrition Society (1972) Symposium on the influence of amino acid supply on polynucleotide and protein metabolism. Proc. Nutr. Soc. 31:249-295.[Medline]
9. Kjeldgaard, N. O. & Kurland, C. G. (1963) The distribution of soluble and ribosomal RNA as a function of growth rate. J. Mol. Biol. 6:341-349.
10. Bergen, W. G. (1974) Protein synthesis in animal models. J. Anim. Sci. 38:1079-1091.
11. Hershey, J.W.B. (1991) Translational control in mammalian cells. Annu. Rev. Biochem. 60:717-755.[Medline]
12. Altmann, M. & Trachsel, H. (1993) Regulation of translation initiation and modulation of cellular physiology. Trends in Biochemical Sciences 18:429-432.[Medline]
13. Moore, P. B. (2000) Concluding remarks for the Helsingor ribosome conference, 13 to 17 June 1999. The Ribosome 2000:555-556 American Society for Microbiology Washington, D.C. .
14. Pyronnet, S. & Sonenberg, N. (2001) Cell-cycle-dependent translational control. Curr. Opin.Genet. Dev. 11:13-18.[Medline]
15. May, M.E. & Buse, M. G. (1989) Effects of branched-chain amino acids on protein turnover. Diabetes Metab. Rev 5:227-245.[Medline]
16. Anthony, J. C., Anthony, T. G., Kimball, S. R. & Jefferson, L. S. (2001) Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J. Nutr. 131:856S-860S.
17. Kimball, S. R. & Jefferson, L. S. (2001) Regulation of protein synthesis by branched-chain amino acids. Curr. Opin. Clin. Nutr. Metab. 4:39-43.[Medline]
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