Altered amino acid metabolism in chronic obstructive pulmonary disease: new therapeutic perspective?

Altered amino acid metabolism in chronic obstructive pulmonary disease: new therapeutic perspective? Engelen MP, Schols AM. Department of Pulmonology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. m.engelen@pul.unimaas.nl PURPOSE OF REVIEW: Wasting of muscle mass, commonly present in patients with chronic obstructive pulmonary disease, is a complex process involving changes in the control of intermediary metabolism as well as in muscle cell status. Although research exploring intermediary metabolism in chronic obstructive pulmonary disease is still in its infancy, there is an increased interest in a potential role for amino acids in modulating muscle anabolism. This review aims at summarizing and critically evaluating the available clinical studies examining alterations in amino acid profile in plasma and skeletal muscle of patients with chronic obstructive pulmonary disease. RECENT FINDINGS: All studies show pronounced alterations in plasma and muscle amino acid status in patients with chronic obstructive pulmonary disease but no consistent "disease specific" pattern for most amino acids. Variability is likely influenced by the heterogeneity of the disease with respect to lung function and nutritional state. Nevertheless, general consistency exists in chronic obstructive pulmonary disease with respect to (1) a reduced plasma branched-chain amino acid level, and (2) a decreased muscle glutamate concentration. Alterations in branched-chain amino acid metabolism appear to be influenced by the degree of muscle wasting, while the reduction in muscle glutamate is related to the diffusing capacity as a hallmark of emphysema. The reduction in glutamate status is associated with reduced muscle glutathione levels and appears to be linked to enhanced glycolysis as evidenced from an accelerated increase in plasma lactate during exercise. SUMMARY: Underlying mechanisms of the observed alterations in amino acid profile in chronic obstructive pulmonary disease, and the influences of disease associated mediators such as chronic low-grade inflammation and (chronic and intermittent) hypoxia are speculative and need to be explored in experimental study design