Effects of Exercise on Amino Acid Metabolism in Patients with Chronic Obstructive Pulmonary Disease

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Abstract
Depletion of fat-free mass (FFM) significantly contributes to de- creased skeletal muscle weakness and impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). FFM wasting suggests disturbances in intermediary metabolism, confirmed by data showing profound alterations in the skeletal muscle amino acid (AA) status in COPD at rest. To unravel whether there is a role for AAs in the mechanisms for skeletal mus- cle dysfunction in COPD, basic knowledge of AA metabolism in the muscle during exercise is important. We examined the effects of 20 min of exercise on AA metabolism in 14 patients with COPD and eight control subjects. Arterialized venous blood and a quad- riceps femoris muscle biopsy were obtained before and immedi- ately after exercise. FFM was not significantly different between the groups. In COPD, a significant reduction of most muscle AAs was present postexercise, whereas several plasma AAs were in- creased (p , 0.05). Consequently, sum AAs was reduced in muscle (20%; p , 0.01) and increased in plasma (16%, p , 0.05), suggest- ing an enhanced AA release from muscle in COPD during exercise. In the COPD group, the increase in plasma alanine and glutamine was even higher postexercise (61%, p , 0.01 and 21%, p , 0.01, respectively), suggesting enhanced nitrogen efflux. This study shows that exercise alters amino acid (intermediary) metabolism in patients with COPD and independent of the presence of FFM wasting. Depletion of fat-free mass (FFM) commonly occurs in chronic obstructive pulmonary disease (COPD) and is an important contributor to skeletal muscle weakness and impaired exercise capacity in these patients (1-3). Depletion of FFM suggests that alterations in intermediary metabolism are present in COPD. Amino acids, the building blocks of proteins, play a pivotal role in intermediary metabolism. There is increasing evidence available pointing toward disturbed amino acid me- tabolism in patients with COPD at rest, as reflected by pro- nounced alterations in the levels of several amino acids in skeletal muscle and plasma (4-7). Skeletal muscle serves as an important reserve system, which under conditions of storage and need maintains sup- plies of amino acids for protein synthesis and metabolism. During short-term exercise and at intensities between 30 and 70% of maximal work rate, skeletal muscle is shown to partic- ipate actively in the metabolism of amino acids in healthy sub- jects (Figure 1). Six amino acids (glutamate (Glu), aspartate, asparagine, and the three branched-chain amino acids) are metabolized in muscle during exercise. As Glu has a central position in all aminotransferase reactions in muscle, the amino group of the six amino acids is interchangeable. In COPD, consistently reduced levels of Glu were found in two different peripheral skeletal muscle groups (quadriceps femoris and tib- ialis anterior muscle) (6, 7), independent of the severity of air- flow obstruction. Glu has various important functions during short-term exercise, such as its role in the establishment and maintenance of a high concentration of tricarboxylic acid (TCA) cycle intermediates, thereby preserving high-energy phosphates during exercise. Moreover, Glu is involved in the synthesis of glutamine (Gln) and alanine (Ala), providing a mechanism for the elimination of amino groups from muscle in the form of nontoxic nitrogen carriers. Evidence has be- come available that the depleted resting Glu status in muscle of patients with COPD plays a role in the early lactate response during maximal exercise in these patients (8). Although substantial disturbances have been found in the amino acid status of the skeletal muscle at rest in COPD, it is unknown whether the amino acid response to exercise is dif- ferent as compared with healthy age-matched controls. Basic knowledge of amino acid metabolism of the skeletal muscle dur- ing exercise may be particularly important to unravel whether there is a potential role for amino acids in the mechanisms of skeletal muscle dysfunction and FFM wasting in patients with COPD. If this is the case, amino acid supplementation may become a potential treatment strategy in these patients. Therefore, the purpose of the present study was to charac- terize the effect of submaximal constant work rate exercise on the (exercise-related) amino acid profile in peripheral skeletal muscle and plasma of patients with COPD, compared with healthy age-matched control subjects. METHODS

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