Fibrinogen Synthesis Is Elevated in Fasting Cancer Patients with an Acute Phase Response

Manuscript received 21 July 1997. Initial reviews completed 26 September 1997. Revision accepted 15 April 1998.

Tom Preston, Christine Slater, Donald C. McMillan^*, J. Stuart Falconer, Alan Shenkin^**, and Kenneth C. H. Fearon

Isotope Biochemistry Laboratory, SURRC, East Kilbride, Glasgow G75 0QF, UK; ^* University Department of Surgery, Royal Infirmary, Glasgow G31 2ER, UK;  University Department of Surgery, Royal Infirmary, Edinburgh EH3 9YW, UK; ^** Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool L69 3GA, UK

The unusual amino acid composition of acute phase proteins may be relevant to our understanding of the mechanism of tissue wasting in chronic inflammatory disease. During periods in which demand for amino acids outstrips dietary supply, skeletal muscle protein may be mobilized to meet this demand. An imbalance in the amino acid composition of these proteins may thus be detrimental to the body's nitrogen economy. To address this problem, we have measured the synthetic rate of fibrinogen (perhaps the major acute phase protein) and plasma amino acid profiles in a group of patients with adenocarcinoma of the pancreas and an ongoing inflammatory response (serum C-reactive protein >10 mg/L in the absence of any other obvious infective or inflammatory cause). These were also measured in a control group with no evidence of inflammation. Fibrinogen synthesis was measured after an overnight fast, using a flooding dose of ²H₅-phenylalanine. The fractional rate of fibrinogen synthesis was significantly elevated in the cancer group compared with healthy controls [39.3 (20.0-49.9) and 21.9 (13.2-37.7) %/d, respectively; median (range), P < 0.05]. The absolute rate of fibrinogen synthesis was also elevated [84 (33-143) and 26 (15-43) mg/(kg·d), respectively; median (range), P < 0.01]. We calculated that, in cancer patients with anorexia-cachexia (i.e., documented ongoing weight loss in the absence of an obvious cause such as obstruction or malabsorption), aromatic amino acid supply (predominantly tryptophan) most limits fibrinogen synthesis from skeletal muscle reserves. Demand for the nonessential amino acids serine and glycine was elevated. Assuming that tryptophan is limiting, up to 2.6 g muscle protein (~12 g skeletal muscle tissue) may be wasted to synthesize 1 g fibrinogen. Interpretation of the observation that circulating free tryptophan concentrations were significantly reduced in the cancer patients will have to await flux measurements. The metabolic changes accompanying the inflammatory response suggest that down-regulation of this process may be beneficial.

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The Journal of Nutrition Vol. 128 No. 8 August 1998, pp. 1355-1360
Copyright ©1998 by the American Society for Nutritional Sciences

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