Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease

Abstract

The objective of this study was to determine whether patients with chronic obstructive lung disease (COPD) display differences in organization of the metabolic pathways and segments involved in energy supply compared with healthy control subjects. Metabolic pathway potential, based on the measurement of the maximal activity (Vmax) of representative enzymes, was assessed in tissue extracted from the vastus lateralis in seven patients with COPD (age 67 ± 4 yr; FEV1/FVC = 44 ± 3%, where FEV1is forced expiratory volume in 1 s and FVC is forced vital capacity; means ± SE) and nine healthy age-matched controls (age 68 ± 2 yr; FEV1/FVC = 75 ± 2%). Compared with control, the COPD patients displayed lower ( P < 0.05) Vmax(mol·kg protein−1·h−1) for cytochrome c oxidase (COX; 21.2 ± 2.0 vs. 28.7 ± 2.2) and 3-hydroxyacyl-CoA dehydrogenase (HADH; 2.54 ± 0.14 vs. 3.74 ± 0.12) but not citrate synthase (CS; 2.20 ± 0.16 vs. 3.19 ± 0.5). While no differences between groups were observed in Vmaxfor creatine phosphokinase, phosphorylase (PHOSPH), phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase, hexokinase (HEX) was elevated in COPD ( P < 0.05). Enzyme activity ratios were higher ( P < 0.05) for HEX/CS, HEX/COX, PHOSPH/HADH and PFK/HADH in COPD compared with control. It is concluded that COPD patients exhibit a reduced potential for both the electron transport system and fat oxidation and an increased potential for glucose phosphorylation while the potential for glycogenolysis and glycolysis remains normal. A comparison of enzyme ratios indicated greater potentials for glucose phosphorylation relative to the citric acid cycle and the electron transport chain and glycogenolysis and glycolysis relative to β-oxidation.