Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a condition characterized by systemic low-grade inflammation that could increase the production of nitric oxide (NO), of which arginine is the sole precursor. Arginine is derived from the breakdown of protein and through the conversion of citrulline to arginine (de novo arginine production).

Objective: Our objective was to study whole-body arginine and citrulline and related metabolism in stable COPD patients.

Design: With the use of stable isotope methodology, we studied whole-body arginine and citrulline rates of appearance, de novo arginine (citrulline-to-arginine flux) and NO (arginine-to-citrulline flux) production, protein synthesis and breakdown rates, and plasma amino acid concentrations in a heterogeneous group of patients with moderate-to-severe COPD [n = 23, mean ± SE age: 65 ± 2 y, forced expiratory volume in 1 s (FEV1): 40% ± 2% of predicted], and a group of healthy older adults (n = 19, mean ± SE age: 64 ± 2 y, FEV1: 95% ± 4% of predicted).

Results: Although plasma arginine and citrulline concentrations were comparable between COPD patients and controls, whole-body arginine (P = 0.015) and citrulline (P = 0.026) rates of appearance were higher in COPD patients and related to a 57% greater de novo arginine production (P < 0.0001). Despite a higher whole-body arginine clearance in COPD patients (P < 0.0001), we found no difference in NO production.

Conclusion: In stable patients with moderate-to-severe COPD, endogenous arginine production is upregulated to support a higher arginine utilization that is unrelated to whole-body NO production. This trial was registered at clinicaltrials.gov as NCT01173354 and NCT01172314.

Keywords: COPD; arginine; citrulline; nitric oxide; protein breakdown.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

Study design. All participants were studied 2 times within 1 wk (≥1 d apart) during a 3-h infusion protocol. t, time.

FIGURE 2

Mean ± SE postabsorptive whole-body Arg rate of appearance (A), citrulline rate of appearance (B), and de novo Arg production (conversion of citrulline to Arg) (C) in healthy controls (n = 19) and COPD patients (n = 23). Statistics were obtained by using 2-factor repeated-measures ANOVA with “group” and “day” used to compare differences between groups and test days. A significant group effect was found, but no significant day effect or interaction. Data are shown as the mean value of both days. *,****Different from controls, *P < 0.05, ****P < 0.0001. COPD, chronic obstructive pulmonary disease; FFM, fat-free mass.

FIGURE 3

Mean ± SE postabsorptive whole-body Arg clearance (A) and NO production (conversion of Arg to citrulline) (B) in healthy controls (n = 19) and COPD patients (n = 23). Statistics were obtained by using 2-factor repeated-measures ANOVA with “group” and “day” used to compare differences between groups and test days. A significant group effect was found for Arg clearance, but no significant day effect or interaction. For NO production, only a significant interaction between group and day was observed (P = 0.0325; Supplemental Figure 5). Data are shown as the mean value of both days. ****Different from controls, P < 0.0001. COPD, chronic obstructive pulmonary disease; FFM, fat-free mass; NO, nitric oxide.