Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease.
To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65 vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.
Green
H J
HJ
Dept. of Kinesiology, Univ. of Waterloo, Waterloo, Ontario, Canada N2L 3G1. green@healthy.uwaterloo.ca
Burnett
M E
ME
D'Arsigny
C L
CL
O'Donnell
D E
DE
Ouyang
J
J
Webb
K A
KA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D015536:Down-Regulation; D004734:Energy Metabolism; D005260:Female; D005541:Forced Expiratory Volume; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000378:metabolism*; D012720:Severity of Illness Index; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
D000255:Adenosine Triphosphate; D005947:Glucose; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006003:Glycogen; D019344:Lactic Acid; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D010725:Phosphocreatine; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human