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New perspectives in the control of body protein metabolism

  • Margaret A. McNurlan (a1)

Recent advances in elucidating the mechanisms that control body protein synthesis and degradation both expand and complicate our understanding of how these processes are regulated. This review presents an introduction to the multiple regulatory systems involved, emphasizing the number of potential controls. These include gene transcription, gene activation or suppression, activation or suppression of mRNA translation and activation or suppression of signaling pathways. The complexity of these interacting controls presents a challenge to our understanding of the overall coordinated regulation of protein synthesis and degradation and its response to any particular stimulus. Specific examples are used to illustrate regulatory mechanisms, including the ways in which protein metabolism is regulated by the amino acid leucine. In addition to regulation associated with gene expression and post-translational control, the expanding field of epigenetics adds another layer of complexity, including trans-generational responses to nutrient intake, highlighting the potential for long-term impact of nutritional experience on the metabolism of subsequent generations.

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*Corresponding author: M. A. McNurlan, email
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1 JM Vaquerizas , SK Kummerfeld , SA Teichmann , et al. (2009) A census of human transcription factors: function, expression and evolution. Nat Rev 10, 252263.

2 SE Malmberg & CM Adams (2008) Insulin signaling and the general amino acid control response. Two distinct pathways to amino acid synthesis and uptake. J Biol Chem 283, 1922919234.

5 G Kaati , LO Bygren & S Edvinsson (2002) Cardiovascular and diabetes mortality determined by nutrition during parents' and grand parents' slow growth period. Eur J Hum Genet 10, 682688.

6 RC Wek , HY Jiang & TG Anthony (2006) Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 34, (Pt 1), 711.

7 MG Buse & SS Reid (1975) Leucine. A possible regulator of protein turnover in muscle. J Clin Invest 56, 12501261.

9 JB Li & LS Jefferson (1978) Influence of amino acid availability on protein turnover in perfused skeletal muscle. Biochimica et Biophysica Acta 544, 351359.

10 L Hagenfeldt , S Eriksson & J Wahren (1980) Influence of leucine on arterial concentrations and regional exchange of amino acids in healthy subjects. Clin Sci (Lond) 59, 173181.

11 MA McNurlan , EB Fern & PJ Garlick (1982) Failure of leucine to stimulate protein synthesis in vivo. Biochem J 204, 831838.

12 WE Mitch , M Walser & DG Sapir (1981) Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man. J Clin Invest 67, 553562.

13 DG Sapir & M Walser (1977) Nitrogen sparing induced early in starvation by infusion of branched-chain ketoacids. Metab: Clin Experi 26, 301308.

14 RS Sherwin (1978) Effect of starvation on the turnover and metabolic response to leucine. J Clin Invest 61, 14711481.

18 R Murgas Torrazza , A Suryawan , MC Gazzaneo , et al. (2010) Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation. J Nutr 140, 21452152.

19 JC Floyd Jr, SS Fajans , S Pek , et al. (1970) Synergistic effect of certain amino acid pairs upon insulin secretion in man. Diabetes 19, 102108.

20 PJ Garlick & I Grant (1988) Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched-chain amino acids. Biochem J 254, 579584.

21 JC Anthony , AK Reiter , TG Anthony , et al. (2002) Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation. Diabetes 51, 928936.

24 CM Ingberg , S Sarnblad , M Palmer , et al. (2003) Body composition in adolescent girls with type 1 diabetes. Diabet Med 20, 10051011.

25 V Desikan , I Mileva , J Garlick , et al. (2010) The effect of oral leucine on protein metabolism in adolescents with type 1 diabetes mellitus. Int J Pediatr Endocrinol 2010, 493258.

26 IL Baptista , ML Leal , GG Artioli , et al. (2010) Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases. Muscle Nerve 41, 800808.

27 T Sugawara , Y Ito , N Nishizawa , et al. (2009) Regulation of muscle protein degradation, not synthesis, by dietary leucine in rats fed a protein-deficient diet. Amino Acids 37, 609616.

29 EL Glynn , CS Fry , MJ Drummond , et al. (2010) Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. J Nutr 140, 19701976.

30 F Tremblay , M Krebs , L Dombrowski , et al. (2005) Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 54, 26742684.

32 M Balage , J Dupont , I Mothe-Satney , et al. (2011) Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance. J Nutr Biochem 22, 219226.

34 I Rieu , M Balage , C Sornet , et al. (2006) Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 575, (Pt 1), 305315.

35 S Verhoeven , K Vanschoonbeek , LB Verdijk , et al. (2009) Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. Am J Clin Nutr 89, 14681475.

36 CH Lang & RA Frost (2005) Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle. J Cell Physiol 203, 144155.

38 I Rieu , C Sornet , J Grizard , et al. (2004) Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats. Experi Gerontol 39, 13151321.

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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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