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August 1988, Vol 123, No. 8 >
ARTICLE | August 1988

Current Concepts of Protein Turnover and Amino Acid Transport in Liver and Skeletal Muscle During Sepsis FREE

Per-Olof Hasselgren, MD, PhD; Peter Pedersen, MD; Harry C. Sax, MD; Brad W. Warner, MD; Josef E. Fischer, MD
[+] Author Affiliations

Accepted for publication June 2, 1987.

Reprint requests to Department of Surgery, University of Cincinnati Medical Center, 231 Bethesda Ave (ML#558), Cincinnati, OH 45267-0558 (Dr Hasselgren).


Arch Surg. 1988;123(8):992-999. doi:10.1001/archsurg.1988.01400320078016
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• The metabolic response to trauma and sepsis is characterized by a negative nitrogen balance, accelerated muscle proteolysis, increased ureagenesis, and stimulated acute-phase protein synthesis in liver. Inhibited uptake of amino acids and accelerated protein breakdown in muscle increase the flux of amino acids from the periphery to the liver. Concomitantly, hepatic uptake of amino acids is stimulated and protein synthesis and gluconeogenesis in the liver are enhanced. These events are important to the survival of patients with sepsis. Stimulated ureagenesis resulting in nitrogen loss from the body is another important aspect of hepatic nitrogen metabolism following trauma and sepsis. The mediator(s) initiating metabolic changes is not yet exactly defined, although regulatory protein(s) released from stimulated macrophages (particularly interleukin 1 and tumor necrosis factor) may play a major role in altered amino acid and protein metabolism in muscle and liver during sepsis. However, these factors alone are probably not responsible for the metabolic disturbances, since the catabolic hormones cortisol, glucagon, and the catecholamines can simulate the metabolic pattern observed in sepsis. Other possible mediators include prostaglandins and thyroid hormones. It is possible that the interaction between different types of mediators is necessary for the full manifestation of host responses to severe injury and sepsis.

(Arch Surg 1988;123:992-999)

REFERENCES

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2 +
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4 +
Hasselgren PO, James JH, Fischer JE:  Inhibited muscle amino acid uptake in sepsis . Ann Surg 1986;;203:360-365.
5 +
Hasselgren PO, Jagenburg R, Karlstrom L, et al:  Changes of protein metabolism in liver and skeletal muscle following trauma complicated by sepsis . J Trauma 1984;;34:224-228.
6 +
Pedersen P, Seeman T, Hasselgren PO:  Protein synthesis and degradation in liver tissue following induction of septic peritonitis in rats . Acta Chir Scand 1986;;152:29-34.
7 +
Beisel WR, Wannemacher RW:  Gluconeogenesis, ureagenesis, and ketogenesis during sepsis . JPEN 1980;;4:277-285.
8 +
Powanda MC:  Plasma proteins and wound healing . Surg Gynecol Obstet 1981;;153:749-755.
9 +
Hasselgren PO, Fischer JE:  Nutritional support in sepsis , in Lang CE (ed): Nutritional Support in Critical Care . Rockville, Md, Aspen Publishers Inc, 1987;, pp 345-361.
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Cuthbertson DP:  Observations on the disturbance of metabolism produced by injury to the limbs . Q J Med 1932;;1:233-246.
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1 +
Aulick LH, Wilmore DW:  Increased peripheral amino acid release following burn injury . Surgery 1979;;85:560-565.
2 +
Rosenblatt S, Clowes GHA, George BC, et al:  Exchange of amino acids by muscle and liver in sepsis: Comparative studies in vivo and in vitro . Arch Surg 1983;;118:167-175.
3 +
Pearl RH, Clowes GHA, Hirsch EF, et al:  Prognosis and survival as determined by visceral amino acid clearance in severe trauma . J Trauma 1985;;25:777-783.
4 +
Hasselgren PO, James JH, Fischer JE:  Inhibited muscle amino acid uptake in sepsis . Ann Surg 1986;;203:360-365.
5 +
Hasselgren PO, Jagenburg R, Karlstrom L, et al:  Changes of protein metabolism in liver and skeletal muscle following trauma complicated by sepsis . J Trauma 1984;;34:224-228.
6 +
Pedersen P, Seeman T, Hasselgren PO:  Protein synthesis and degradation in liver tissue following induction of septic peritonitis in rats . Acta Chir Scand 1986;;152:29-34.
7 +
Beisel WR, Wannemacher RW:  Gluconeogenesis, ureagenesis, and ketogenesis during sepsis . JPEN 1980;;4:277-285.
8 +
Powanda MC:  Plasma proteins and wound healing . Surg Gynecol Obstet 1981;;153:749-755.
9 +
Hasselgren PO, Fischer JE:  Nutritional support in sepsis , in Lang CE (ed): Nutritional Support in Critical Care . Rockville, Md, Aspen Publishers Inc, 1987;, pp 345-361.
10 +
Cuthbertson DP:  Observations on the disturbance of metabolism produced by injury to the limbs . Q J Med 1932;;1:233-246.
11 +
O'Donnell TF, Clowes GHA, Blackburn GL, et al:  Proteolysis associated with a deficit of peripheral energy fuel substrates in septic man . Ann Surg 1976;;80:192-200.
12 +
Williamson DH, Farrell R, Kerr A, et al:  Muscle protein catabolism after injury in man, as measured by urinary excretion of 3-methyl-histidine . Clin Sci 1977;;52:527-533.
13 +
Clowes GHA, George BC, Villee CA, et al:  Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma . N Engl J Med 1983;;308:545-552.
14 +
Tischler ME, Fagan JM:  Response to trauma of protein, amino acids, and carbohydrate metabolism in injured and uninjured rat skeletal muscles . Metabolism 1983;;32:853-868.
15 +
Clark AS, Kelly RA, Mitch WE:  Systemic response to thermal injury in rats: Accelerated protein degradation and altered glucose utilization in muscle . J Clin Invest 1984;;74:888-897.
16 +
Hasselgren PO, Talamini MA, James JH, et al:  Protein metabolism in different types of skeletal muscle during early and late sepsis in rats . Arch Surg 1986;;121:918-923.
17 +
Ruff RL, Secrist D:  Inhibitors of prostaglandin synthesis or cathepsin B prevent muscle wasting due to sepsis in the rat . J Clin Invest 1984;;73: 1483-1486.
18 +
Ryan NT:  Metabolic adaptations for energy production during trauma and sepsis . Surg Clin North Am 1976;;56:1073-1090.
19 +
Stein TP, Oram-Smith JC, Wallace HW, et al:  The effect of trauma on protein synthesis . J Surg Res 1976;;21:201-203.
20 +
O'Keefe SJD, Sender PM, James WPT:  'Catabolic' loss of body nitrogen in response to surgery . Lancet 1974;;2:1035-1038.
21 +
Freund H, Yoshimura N, Fischer JE:  The effect of branched chain amino acids and hypertonic glucose infusion on post-injury catabolism in the rat . Surgery 1980;;87:401-408.
22 +
Jepson MM, Pell JM, Bates PC, et al:  The effects of endotoxaemia on protein metabolism in skeletal muscle and liver of fed and fasted rats . Biochem J 1986;;235:329-336.
23 +
Rennie MJ, Edwards RHT, Emery PW, et al:  Depressed protein synthesis is the dominant characteristic of muscle wasting and cachexia . Clin Physiol 1983;;3:387-398.
24 +
Rennie MJ, Harrison R:  Effects of injury, disease, and malnutrition on protein metabolism in man: Unanswered questions . Lancet 1984;;1:323-325.
25 +
Hasselgren PO, James JH, Warner BW, et al: Protein synthesis and degradation in skeletal muscle from septic rats: Response to leucine and α-ketoisocaproic acid. Arch Surg, in press.
26 +
Buse MG, Reid SS: Leucine:  A possible regulator of protein turnover in muscle . J Clin Invest 1975;;56:1250-1261.
27 +
Tischler ME, Desautels M, Goldberg AL:  Does leucine, leucyl-tRNA, or some metabolite of leucine regulate protein synthesis and degradation in skeletal and cardiac muscle? J Biol Chem 1982;;257:1613-1621.
28 +
Hasselgren PO, Warner BW, James JH, et al:  Effect of insulin on amino acid uptake and protein turnover in skeletal muscle from septic rats: Evidence for insulin resistance of protein breakdown . Arch Surg 1987;;122: 228-233.
29 +
Wannemacher RW, Powanda MC, Dinterman RE:  Amino acid flux and protein synthesis after exposure of rats to either Diplococcus pneumoniae or Salmonella typhimurium . Infect Immun 1974;;10:60-65.
30 +
Kuttner RE, Spitzer JJ:  The effect of endotoxin on plasma α-aminoisobutyric acid . Experientia 1980;;36:215-216.
31 +
Karlstad MD, Sayeed MM:  α-Aminoisobutyric acid transport in rat soleus muscle during endotoxic shock . Am J Physiol 1985;;248:R142-R146.
32 +
Neuhaus OW, Balegno HF, Chandler AM:  Induction of plasma protein synthesis in response to trauma . Am J Physiol 1966;;211:151-156.
33 +
Schumer W, Molnar J, Dowling JN, et al:  Biosynthesis of glycoproteins: Effect of injury on serumucoid fraction of rat plasma . Am J Physiol 1967;;212:184-190.
34 +
Little JS:  Synthesis, transport, and secretion of plasma proteins by the livers of control and Streptococcus pneumoniae—infected rats . Infect Immun 1978;;22:585-596.
35 +
Schreiber G, Howlett G:  Synthesis and secretion of acute-phase proteins , in Glaumann H, Peters T, Redman C (eds): Plasma Protein Secretion by the Liver . Orlando, Fla, Academic Press Inc, 1983;, pp 423-449.
36 +
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