Enhanced levels of whole-body protein turnover in patients with chronic obstructive pulmonary disease.
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-(2)H(5)]phenylalanine (Phe) and L-[ring-(2)H(2)]tyrosine. Because there is evidence for specific disturbances in leucine (Leu) metabolism, the PB values were compared with those obtained when infusing L-[1-(13)C]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.
Engelen
M P
MP
Departments of Pulmonology and Surgery, Maastricht University, Maastricht, The Netherlands. M.Engelen@Pul.Unimaas.nl
Deutz
N E
NE
Wouters
E F
EF
Schols
A M
AM
D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008173:Lung Diseases, Obstructive / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011506:Proteins / Q000378:metabolism*; D019282:Wasting Syndrome / Q000503:physiopathology*; D014915:Whole-Body Counting
D000596:Amino Acids; D002250:Carbon Radioisotopes; D011506:Proteins; D007930:Leucine