Engelen M P, Deutz N E, Wouters E F, Schols A M
Departments of Pulmonology and Surgery, Maastricht University, Maastricht, The Netherlands.
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1488-92. doi: 10.1164/ajrccm.162.4.2002045.
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.
大量慢性阻塞性肺疾病（COPD）患者的特征是无脂肪体重消耗以及肌肉和血浆氨基酸水平改变，这表明蛋白质代谢发生了变化。在本研究中，我们检查了14名稳定期COPD患者和8名健康对照者的全身蛋白质分解（PB）和合成（PS）是否存在差异。通过联合输注稳定同位素L-[环-(2)H(5)]苯丙氨酸（Phe）和L-[环-(2)H(2)]酪氨酸来测量全身PB、PS和净PB（=PB - PS）。由于有证据表明亮氨酸（Leu）代谢存在特定紊乱，因此将PB值与输注L-[1-(13)C]Leu示踪剂时获得的值进行比较。在动脉化静脉血浆和股外侧肌中测量同位素富集值和氨基酸浓度。通过Phe和Tyr示踪剂评估的全身PS和PB在COPD组中高于对照组（p < 0.05），表明蛋白质周转率升高。两组的净PB均增加，表明在吸收后状态下蛋白质分解代谢程度相当。相比之下，通过Leu示踪剂测定的全身PB在两组之间没有差异。因此，COPD组中Leu与Phe分解的比率降低（p < 0.001）。此外，在COPD组中，发现Leu的肌肉与血浆梯度较高（p < 0.001），而Phe则不然。本研究揭示了COPD患者蛋白质周转率升高，并表明输注Leu示踪剂反映了这些患者的Leu代谢，但不能反映全身蛋白质代谢。
