Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC–MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear.
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July 2016
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Sagittal section through the retina of a hypertensive dTGR rat: staining in blue (DAPI) of cell nuclei and in red GFAP (glial fibrillary acidic protein). The GFAP staining shows activated astrocytes in the ganglion cell layer of the retina. See pp. 1075–1088 for further details. Image kindly provided by Olaf Strauß.
Research Article|
June 01 2016
Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis
Mariëlle P.K.J. Engelen;
*Center for Translational Research in Aging & Longevity, Health and Kinesiology, Texas A&M University, College Station, TX 77843, U.S.A.
†Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
Correspondence: Mariëlle P.K.J. Engelen (email [email protected]).
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Ahmed M. Safar;
Ahmed M. Safar
‡Department of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
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Thaddeus Bartter;
Thaddeus Bartter
§Department of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
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Fari Koeman;
Fari Koeman
*Center for Translational Research in Aging & Longevity, Health and Kinesiology, Texas A&M University, College Station, TX 77843, U.S.A.
†Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
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Nicolaas E.P. Deutz
Nicolaas E.P. Deutz
*Center for Translational Research in Aging & Longevity, Health and Kinesiology, Texas A&M University, College Station, TX 77843, U.S.A.
†Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
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Publisher: Portland Press Ltd
Received:
December 15 2015
Revision Received:
April 04 2016
Accepted:
April 05 2016
Accepted Manuscript online:
April 07 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (14): 1185–1195.
Article history
Received:
December 15 2015
Revision Received:
April 04 2016
Accepted:
April 05 2016
Accepted Manuscript online:
April 07 2016
Citation
Mariëlle P.K.J. Engelen, Ahmed M. Safar, Thaddeus Bartter, Fari Koeman, Nicolaas E.P. Deutz; Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis. Clin Sci (Lond) 1 July 2016; 130 (14): 1185–1195. doi: https://doi.org/10.1042/CS20160233
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