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

Jonker, Renate; Deutz, N.E.P.; Erbland, Marcia L.; Anderson, Paula; Engelen, M.P.

doi:10.3945/ajcn.115.125187

Cited by 29 publications

(27 citation statements)

References 46 publications

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“…Diffusion capacity (D LCO ) from the medical record was available for n=15 COPD patients, of which n=9 had a moderate to severe reduction in diffusing capacity (D LCO < 60% of predicted). As previously published [19], gender division, age (64±2 vs. 65±2 y), BMI (27.8±1.1 vs. 26.3±1.0 kg/m 2 ), and fat-free mass index (17.7±0.6 vs. 17.0±0.5 kg/m 2 ) were all similar between the controls and COPD patients. Furthermore, COPD patients varied in comorbidities and exacerbation frequency [19].…”

Section: Resultssupporting

confidence: 80%

“…As previously published [19], gender division, age (64±2 vs. 65±2 y), BMI (27.8±1.1 vs. 26.3±1.0 kg/m 2 ), and fat-free mass index (17.7±0.6 vs. 17.0±0.5 kg/m 2 ) were all similar between the controls and COPD patients. Furthermore, COPD patients varied in comorbidities and exacerbation frequency [19]. Fasting glucose (5.7±0.2 vs. 5.2±0.1 mmol/L), insulin (8.0± 1.2 vs. 8.7±1.1 μIU/mL), and HOMA-IR (1.16±0.16 vs. 1.22±0.15) were not different between the groups.…”

Section: Resultssupporting

confidence: 80%

“…As previously described [19], this contributed to an overall lower plasma EAA concentration in COPD patients.…”

Section: Resultssupporting

confidence: 64%

“…Postabsorptive values for whole body protein turnover did not differ between controls and COPD patients [19]. Figure 4A and Supplemental Figure 4 illustrate that in both groups there was an excellent positive linear relationship between the amount of PHE (r=0.84–0.91, P <0.001) and total EAAs (r=0.73–0.81, P <0.0001) consumed and net protein gain.…”

Section: Resultsmentioning

confidence: 99%

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Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults

et al. 2017

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Background The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults. Methods According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65 ± 2 y, FEV1: 40 ± 2% of predicted) and 19 healthy age-matched subjects (age: 64 ± 2 y), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures). Results Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84–0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance. Conclusions In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population. Trial registry ClinicalTrials.gov; Nos.: NCT01173354 and NCT01172314; URL: www.clinicaltrials.gov

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Section: Resultssupporting

confidence: 80%

Section: Resultssupporting

confidence: 80%

“…As previously described [19], this contributed to an overall lower plasma EAA concentration in COPD patients.…”

Section: Resultssupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

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Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults

et al. 2017

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“…As a semi-essential amino acid, L-arginine can be provided by an endogenous and an exogenous source. The kidney can subsist a basal L-arginine de-novo synthesis [4, 12], but especially during a high L-arginine demand, like growth, inflammation or wound healing processes, L-arginine-rich food intake is pivotal for the sustain of an adequate supply [4, 13, 14]. Hence, a dietary intake of L-arginine of 1-3g/d through food is recommended [4, 15].…”

Section: Introductionmentioning

confidence: 99%

Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats

Kitay

Link

Geibel

2017

Cell Physiol Biochem

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Background/Aims: L-arginine is an important mediator of cell division, wound healing, and immune function. It can be transformed by the nitric oxide synthase (NOS) to nitric oxide (NO), an important cell signaling molecule. Recent studies from our laboratory demonstrate specific effects of L-arginine (10mM) exposure on gastric acid secretion in rat parietal cells. Methods: Studies were performed with isolated gastric glands and the pH sensitive dye BCECF-AM +/- L-arginine to examine its effects on acid secretion. The direct NO-donor diethylamine NONOate sodium salt hydrate, was also used while monitoring intracellular pH. The specific inhibitor of the intracellular NO signal cascade ODQ was also used. Results: We found that gastric proton extrusion was activated with application of L-arginine (10mM), in a separate series when L-arginine (10mM) + L-NAME (30µM) were added there was no acid secretion. Addition of the NO-donor diethylamine NONOate sodium salt hydrate (10µM) also induced acid secretion. When the selective sGC-inhibitor ODQ was added with NONOate we did not observe acid secretion. Conclusion: We conclude that L-arginine is a novel secretagogue, which can mediate gastric acid secretion. Furthermore, the intake of L-arginine causes direct activation of the H⁺, K⁺ ATPase and increased proton extrusion from parietal cells resulting in the increased risk for acid-related diseases. The NO/sGC/cGMP pathway has never been described as a possible intracellular mechanism for H⁺, K⁺ ATPase activation before and presents a completely new scientific finding. Moreover, our studies demonstrate a novel role for L-NAME to effectively eliminate NOS induced acid secretion and thereby reducing the risk for L-arginine inducible ulcer disease.

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Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation

et al. 2021

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Intensive care unit patients and chronic airway inflammatory disease are characterized by chronic systemic hypoxia and inflammation inducing a decrease in nitric oxide release due to impaired L-arginine (ARG) homeostasis. As ARG is synthesized from circulating L-citrulline (CIT), an alteration of CIT production in small intestine by ornithine carbamoyltransferase could be involved. Here, we posit that hypoxia and/or inflammation has effects on ornithine carbamoyltransferase regulation in enterocytes. A duodenal explant incubation model was used. Biopsy specimens taken from 25 selected patients were incubated for 6 h in 4 groups: control, inflammation, hypoxia, and hypoxia + inflammation. At the end of the incubation period, we measured CIT concentration in culture media, ornithine carbamoyltransferase activity, ornithine carbamoyltransferase protein and gene expression, protein expression of enzymes involved in the CIT production pathway, and expression of energy status proteins. Inflammation and/or hypoxia conditions did not affect CIT production. Ornithine carbamoyltransferase activity was increased in hypoxia conditions (p = 0.023). Expression of enzymes implicated in the CIT crossroads pathway and enzymes reflecting energy status variation was not affected by inflammation and hypoxia. Data sets were pooled to evaluate the variability of the four quartiles for each parameter. CIT production was found to increase over the quartiles whereas other parameters remained stable. Our results showed that intestinal CIT production is preserved during inflammation and/or hypoxia, thus confirming the significance of this metabolic pathway. This suggests that the CIT deficiency observed in clinical hypercatabolic states could be a consequence of high utilization for ARG synthesis.

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

Abstract: 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.

Cited by 29 publications

References 46 publications

Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults

Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults

Activation of Secretagogue Independent Gastric Acid Secretion via Endothelial Nitric Oxide Synthase Stimulation in Rats

Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation

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