Lysine and homoarginine are closely interrelated metabolites in the rat

Abstract

L-Lysine (Lys) and L-arginine (Arg), but not L-homoarginine (hArg), are proteinogenic amino acids. In healthy humans, oral administration of hArg increased the plasma concentration of Lys, suggesting Lys as a metabolite of hArg. In humans and animals, hArg is biosynthesized from Arg and Lys by arginine:glycine amidinotransferase (AGAT). In vitro, recombinant human arginase and bovine liver arginase I hydrolyzed hArg to Lys, suggesting Lys as a metabolite of hArg. The aim of the present study was to investigate whether changes in blood concentrations of hArg and Lys in old rats fed for 4 months with varied controlled experimental diets could suggest interconversion of these amino acids. Blood samples (n = 253) were taken before (T0) and after 2 months (T2) and 4 months (T4) of the experiment. Plasma concentrations of Lys and hArg were determined by gas chromatography–mass spectrometry. The plasma hArg concentration markedly correlated with the plasma Lys concentration at all timepoints (r ≥ 0.7, P < 0.0001). Further analysis demonstrated that hArg and Lys are closely and specifically associated independently of experimental time/rat age and diet, suggesting that hArg and Lys are mutual metabolites in old rats. Based on the plasma concentration changes, the median yield of hArg from Lys was determined to be 0.17% at T0 and each 0.27% at T2 and T4. With a circulating concentration of about 3 µM, hArg a major metabolite of Lys in healthy humans. hArg supplementation is currently investigated as a cardioprotective means to improve impaired hArg synthesis. Present knowledge suggests that Lys rather than hArg supplementation may be even more favorable.

Determination of equilibria constants of arginine:glycine amidinotransferase (AGAT)-catalyzed reactions using concentrations of circulating amino acids

“…Supplementary Cit has a therapeutic potential as a source of Arg in health and diseases associated with Arg deficiency (Schwedhelm et al 2007;Rashid et al 2020). (Bollenbach et al 2019) and in rats (Baskal et al 2022b). In the AGAT pathway, Lys is the second substrate needed to produce hArg.…”

Homoarginine in health and disease

“…Arginase hydrolyzes hArg to Lys, yet the activity of arginase is several orders of magnitude lower than the hydrolysis of Arg to Orn [15]. hArg and Lys are closely inter-related metabolites in humans [15] and rats [16 ▪▪ ]. Yet, it seems that Lys is metabolically favoured.…”

Homoarginine in the cardiovascular system: Pathophysiology and recent developments

“…42,56,57,[59][60][61] Another catabolic pathway of L-hArg is catalyzed by L-arginase hydrolyzing L-hArg to urea and lysine. 62 However, the ability of L-hArg to serve as an alternative substrate for arginase requires further research.…”