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Couchet M, Pestour S, Breuillard C, et al. Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation. Biofactors. 2021;doi: 10.1002/biof.1810.
Couchet, M., Pestour, S., Breuillard, C., Corne, C., Rendu, J., Fontaine, E., & Moinard, C. (2021). Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation. BioFactors (Oxford, England), . https://doi.org/10.1002/biof.1810
Couchet, Morgane, et al. "Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation." BioFactors (Oxford, England) vol. (2021). doi: https://doi.org/10.1002/biof.1810
Couchet M, Pestour S, Breuillard C, Corne C, Rendu J, Fontaine E, Moinard C. Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation. Biofactors. 2021 Dec 09; doi: 10.1002/biof.1810. Epub 2021 Dec 09. PMID: 34882863.
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Biofactors. 2021 Dec 09; doi: 10.1002/biof.1810. Epub 2021 Dec 09.

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

BioFactors (Oxford, England)

Morgane Couchet, Sandie Pestour, Charlotte Breuillard, Christelle Corne, John Rendu, Eric Fontaine, Christophe Moinard

Affiliations

  1. Université Grenoble-Alpes, Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U 1055, Grenoble, France.
  2. Centre Hospitalier Universitaire Grenoble-Alpes, Grenoble, France.

PMID: 34882863 DOI: 10.1002/biof.1810

Abstract

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.

© 2021 International Union of Biochemistry and Molecular Biology.

Keywords: amino acid; duodenum; metabolism; ornithine carbamoyltransferase; sepsis

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