title: Metabolic profiling detects biomarkers of protein degradation in COPD patients.
abstract: There is a paucity of biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics were applied to a defined COPD patient cohort from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points). Results were correlated with accepted biomarkers for the disease. Baseline control serum (n=66) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (n=70), III (n=64) and IV (n=44) COPD patients were analysed by proton nuclear magnetic resonance ((1)H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to confirm amino acid changes detected by (1)H NMR. Data were correlated with body composition, emphysema and systemic inflammation. (1)H NMR identified decreased lipoproteins, N,N-dimethylglycine, and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branched-chain amino acids (BCAAs) observed in GOLD stage IV patients. BCAAs, their degradation products, 3-methylhistidine, ketone bodies, and triglycerides were correlated negatively with cachexia and positively with systemic inflammation. Emphysema patients also displayed decreased serum creatine, glycine and N,N-dimethylglycine. LC-MS/MS confirmed (1)H NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD stage IV patients. NMR-based metabolomics characterised COPD patients based on systemic effects and lung function parameters. Increased protein turnover occurred in all COPD patients with increased protein degradation in individuals with emphysema and cachexia.
authors.affiliation: Dept of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, UK.
authors.forename: Baljit K
authors.initials: BK
authors.lastname: Ubhi
authors.forename: John H
authors.initials: JH
authors.lastname: Riley
authors.forename: Paul A
authors.initials: PA
authors.lastname: Shaw
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.forename: Susan C
authors.initials: SC
authors.lastname: Connor
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000737:chemistry; D015415:Biomarkers / Q000378:metabolism*; D015992:Body Mass Index; D002853:Chromatography, Liquid / Q000379:methods; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009752:Nutritional Status; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D011506:Proteins