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Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1488-1492

Enhanced Levels of Whole-body Protein Turnover in Patients with Chronic Obstructive Pulmonary Disease

MARIËLLE P. K. J. ENGELEN, NICOLAAS E. P. DEUTZ, EMIEL F. M. WOUTERS, and ANNEMIE M. W. J. SCHOLS

Departments of Pulmonology and Surgery, Maastricht University, Maastricht, The Netherlands

A substantial number of patients with chronic obstructive pulmonary disease (COPD) are characterized by fat-free mass wasting and altered muscle and plasma amino acid levels, suggesting changes in protein metabolism. In the present study, we examined whether whole-body protein breakdown (PB) and synthesis (PS) differ between 14 stable patients with COPD and 8 healthy controls. Whole-body PB, PS, and net PB (= PB-PS) were measured by the combined infusion of the stable isotopes L-[ring-2H5]phenylalanine (Phe) and L-[ring-2H2]tyrosine. Because there is evidence for specific disturbances in leucine (Leu) metabolism, the PB values were compared with those obtained when infusing L-[1-13C]Leu tracer. In arterialized-venous plasma and in vastus lateralis muscle, the isotope enrichment values and amino acid concentrations were measured. Whole-body PS and PB, assessed by Phe and Tyr tracer, were higher in the COPD group than in the control group (p < 0.05), indicating an elevated protein turnover. Net PB was increased in both groups, indicating a comparable degree of protein catabolism in the postabsorptive state. In contrast, whole-body PB determined by Leu tracer was not different between the groups. As a consequence, the ratio of Leu to Phe breakdown was reduced in the COPD group (p < 0.001). Moreover, in the COPD group a higher muscle-to-plasma gradient was found for Leu (p < 0.001) but not for Phe. The present study reveals elevated levels for protein turnover in patients with COPD, and indicates that infusion of the Leu tracer gives a reflection of Leu metabolism but not of whole-body protein metabolism in these patients.




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