title: Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.
abstract: 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.
authors.affiliation: 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. mpkj.engelen@ctral.org.
authors.forename: Mariëlle P K J
authors.initials: MP
authors.lastname: Engelen
authors.affiliation: Department of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Safar
authors.affiliation: Department of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Bartter
authors.affiliation: 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.
authors.forename: Fari
authors.initials: F
authors.lastname: Koeman
authors.affiliation: 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.
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002956:Citrulline / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*
chemical_list: D000596:Amino Acids; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine
keywords: dietary amino acids; endogenous arginine synthesis; nitric oxide synthesis; non-small cell lung cancer; stable isotope methodology; systemic arginine availability