Original articleClinicalEnzyme Catalytic Activities in Chronic Obstructive Pulmonary Disease
Introduction
Chronic obstructive pulmonary disease (COPD) is a condition characterized by reduced airflow through the airways, which is irreversible, generally progressive and associated with pulmonary inflammatory hyperresponsiveness to adverse particles and gases (1). The disease definition is focused exclusively on the lungs; therefore, it is not surprising that only pulmonary parameters such as 1-sec forced expiratory volume (FEV1) or arterial oxygen pressure (PaO2) are considered in the disease grading and prognosis, with lungs being the main therapeutic target (2).
Recently it has been discovered that COPD is associated with other extrapulmonary effects, so-called systemic COPD effects, in addition to the typical pulmonary pathology 1, 3, 4. These systemic effects of COPD appear to be of high clinical relevance, as they may contribute to the better understanding, classification and management of the disease. The systemic effects of COPD described to date include systemic inflammation 1, 5, oxidative stress, activation of inflammatory cells (neutrophils and lymphocytes) (6), nutritional abnormalities and weight loss (7), abnormal amino acid metabolism (8), skeletal muscle dysfunction, muscle mass wasting (9), osteoskeletal effects (10), cardiovascular effects (11), nervous system effects (12), etc.
As recently reported, skeletal muscle dysfunction contributes significantly to the reduced exercise tolerance as a general complaint in COPD patients (9). Skeletal muscle dysfunction as a feature common to all COPD patients, contributing significantly to their reduced exercise capacity and quality of life, has been substantiated in a number of studies 9, 13. This has definitely helped in better defining the role of physical activity, rehabilitation programs and nutrition in the clinical management of COPD (14). Skeletal muscle dysfunction in COPD has been intensively investigated; however, its mechanism has not yet been fully elucidated. Involvement of different yet inter-related mechanisms such as sedation (15), nutritional abnormalities 1, 16, tissue hypoxia (17), systemic inflammation 1, 18, 19, oxidative stress 4, 20, hormone changes and electrolyte balance changes (15), cigarette smoking 15, 21, and others have been proposed. These mechanisms are not exclusively associated with COPD but also with other chronic diseases, e.g., cardiac and renal diseases, acquired immunodeficiency syndrome, and carcinoma 9, 15.
The aim of the present study was to determine the activities of the enzymes specifically involved in the metabolism of amino acids (aspartate aminotransferase, ALT; alanine aminotransferase, AST; and gamma-glutamyltransferase, GGT) in COPD patient sera to help clarify skeletal muscle wasting and dysfunction, i.e., changes in the metabolism of amino acids, in COPD. In addition, the activities of lactate dehydrogenase (LDH), the enzyme involved in the anaerobic phase of glycolysis, and alkaline phosphatase (ALP), a membrane enzyme, were also determined. Considering the major role of cigarette smoking in the pathogenesis of COPD, another aim was to assess the effect of smoking on these enzyme activities.
Section snippets
Subjects
The study included 58 healthy male subjects, mean age 53 years [range 40–72 years; body mass index (BMI) of all volunteers = 27.4 ± 3.4; BMI of smokers only = 27.6 ± 4.4] and 29 COPD male patients, mean age 66 years (range 44–80 years; BMI = 26.0 ± 4.4) (group 4). The group of healthy subjects consisted of 21 nonsmokers (group 1), 17 ex-smokers (group 2) and 20 smokers (group 3; pack/year = 36.2 ± 9.4). Upon approval issued by the local Ethics Committee, all study subjects signed an informed
Methods
The catalytic activity of AST, ALT, ALP, GGT and LDH was determined by standardized methods 22, 23, 24, 25, 26 on an Olympus AU400 selective autoanalyzer using reagents from the same manufacturer.
Microsoft Office Excel 2000 software (Microsoft Corp., Redmond, WA) was used on data storage and processing for statistical analysis. Quantitative variables were expressed by arithmetic mean (), standard deviation (SD), median (M), range, and centiles. Between-group difference was tested by
Results
Absolute values of enzyme catalytic activities in the sera of study subjects, expressed as mean, median and range, are presented in Table 1, and as centile values in Figure 1A and 1B and Figure 2A–2C. Statistical analysis showed the mean value of AST catalytic activity to be significantly lower in COPD patients vs. group 1, 2 and 3 subjects (p <0.001), and that of ALT catalytic activity only vs. group 1 (nonsmokers) (p <0.05).
Centile values revealed 95% of COPD patients to have lower AST
Discussion
The understanding of COPD pathogenesis has been considerably upgraded in the last few decades. Today it is well known that in addition to airflow obstruction, coughing and sputum formation, COPD characteristics also include various systemic effects such as systemic inflammation and systemic oxidative stress, muscle mass and body mass wasting, skeletal muscle dysfunction, amino acid metabolism impairment, etc. 1, 3, 4, 5, 7, 8, 9, 29, 30, 31. Systemic effects are by no means infrequently the
Acknowledgments
The authors wish to thank Vesna Baricevic for excellent technical assistance.
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Lactate dehydrogenase isoenzymes in patients with acute exacerbation of chronic obstructive pulmonary disease: An exploratory cross-sectional study
2021, Respiratory Physiology and NeurobiologyCitation Excerpt :This result proves the correlation of LDH with severe inflammation and deterioration of pulmonary function. In another study, the activity of LDH was increased in sera of COPD patients as compared with a group of healthy nonsmokers, thus supporting the hypothesis of altered amino acid metabolism in skeletal muscle in COPD (Cepelak et al., 2006), whereas another study found moderate positive correlation between C-reactive protein (CRP) and LDH3 isoenzyme (Nillawar et al., 2012). Among 178 COPD patients, those with normal serum LDH values had statistically significant less dyspnea and higher exercise capacity than those with higher values (Spruit et al., 2008).
Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry
2019, BiochimieCitation Excerpt :On the other hand the diminution of aspartic acid in LC patients could be associated to the decreased activity of aspartate aminotransferase which catalyzes the transfer reaction of an amino group from l-aspartate to 2-oxoglutarate, forming l-glutamate and oxaloacetate. Cepelak et al. reported a decrease of this enzyme in serum of COPD patients when compared with the group of healthy non-smokers [49]. Finally, lipids play an important role in the pathogenesis of COPD [39].
Muscle catabolism in patients with chronic obstructive pulmonary disease
2011, Revista Clinica EspanolaNo effect of glutamine ingestion on indices of oxidative metabolism in stable COPD
2011, Respiratory Physiology and NeurobiologyCitation Excerpt :There is no evidence to suggest that either the system Nm amino acid transporter or glutaminase activity are adversely affected in this patient group. However, it is plausible that intramuscular alanine aminotransferase activity is reduced in COPD since this has been shown in the sera of COPD as compared to healthy controls (Cepelak et al., 2006). Though unlikely, it is possible therefore that glutamine ingestion did not result in TCAi pool expansion as previously observed in controls (Bruce et al., 2001) since we were unable to experimentally confirm this.
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2011, Revista de Patologia RespiratoriaGamma-Glutamyltransferase Activity and Total Antioxidant Status in Serum and Platelets of Patients with Community-acquired Pneumonia
2007, Archives of Medical ResearchCitation Excerpt :Our patients had elevated platelet GGT catalytic activity throughout their hospital stay, suggesting a major role of the enzyme in the antioxidant defense during the course of pneumonia. In platelets, like other cells, glutathione probably undergoes continuous, GGT-mediated GSH cycling to maintain oxidative/antioxidative balance (57). According to the study by Katsoulis et al., serum TAS concentration in pneumonia patients reflects the disease severity because it was decreased in these patients (58).