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Impact of enteral arginine supplementation on lysine metabolism in humans: A proof‐of‐concept for lysine‐related inborn errors of metabolism
Author(s) -
Schmidt Zoe,
Murthy Gayathri,
Ennis Madeleine,
StocklerIpsiroglu Sylvia,
Elango Rajavel
Publication year - 2020
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12233
Subject(s) - lysine , arginine , enteral administration , metabolism , amino acid , biochemistry , chemistry , pharmacology , medicine , parenteral nutrition
Patients with lysine‐related inborn errors of metabolism (pyridoxine‐dependent epilepsy [PDE] and glutaric aciduria type 1 [GA1]), follow a lysine‐restricted diet with arginine‐fortified lysine‐free amino acid formula and additional oral arginine supplementation as a newer therapy for PDE. The rationale of arginine supplementation is based on arginine's ability to compete with lysine transport across cell membranes via shared transporter systems. Adequate doses of arginine required to competitively inhibit enteral lysine uptake has not been studied in humans This proof‐of‐concept study investigates the effect of incremental enteral arginine doses on whole‐body lysine oxidation using an in vivo stable isotope tracer, L‐[1‐ 13 C] lysine, in healthy humans. Five healthy men completed six study days each consuming one dose of l ‐arginine HCl per study day; range = 50‐600 mg/kg/d. Lysine intake was at DRI (30 mg/kg/d). Breath samples were analysed for L‐[1‐ 13 C] lysine oxidation to 13 CO 2 using an isotope ratio mass spectrometer. Plasma amino acid concentrations were analysed using an amino acid analyser. Increasing doses of l ‐arginine HCl caused a linear decrease in whole‐body lysine oxidation. Plasma arginine concentration increased, and plasma lysine concentration decreased below normal range with high arginine intakes. We provide the first empirical evidence of arginine‐lysine antagonism in response to increasing oral arginine doses. Results suggest 300‐600 mg/kg/d of l ‐arginine HCl and lysine intake restricted to DRI is needed to reduce enteral lysine uptake and systemic lysine oxidation. This could potentially lead to a recommended dose for arginine in lysine‐related inborn errors of metabolism.