Homoarginine in health and disease

Abstract

Purpose of reviewHomoarginine (hArg) is an endogenous, nonproteinogenic amino acid. It is enzymatically synthesized from L-arginine and L-lysine. Low hArg concentrations appear to be a risk factor in the renal and cardiovascular systems. This review discusses advances in-vitro and in-vivo experimental and clinical research on hArg in health and disease.Recent findingsRecent studies indicate that low circulating and low urinary concentrations of hArg are associated with morbidity and worse outcome. Although the biological activities of hArg remain still unexplored, hArg supplementation is intensely investigated as a strategy to increase hArg concentration to reach normal levels in cases of low hArg concentrations. The greatest changes in circulating hArg concentrations are observed during pregnancy and after delivery. In healthy adults, a daily dose of 125 mg hArg seems to be optimum to normalize circulating levels. Short-term supplementation of inorganic nitrate enhances hArg biosynthesis in healthy young men. Apart from hArg supplementation, dietary L-arginine and L-citrulline appear to be a promising alternative.SummaryConsiderable progress has been made in recent years, but hArg remains still enigmatic. Further research is required to explore the biological activities of hArg. Supplementation of hArg or its precursors L-citrulline/L-arginine seem to be promising strategies to prevent and overcome altered hArg synthesis.

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease

“…These metabolites have also been associated with the consumption of vegetables and plant-based diets rich in legumes [ 43 , 44 ], both with recognized cardiometabolic benefits [ 45 ], especially in relation to glucose metabolism. N-acetylornithine plays a role in arginine synthesis [ 43 , 46 ], and homoarginine is related to the metabolism of arginine and lysine [ 47 ]. Arginine has previously been linked with enhanced insulin secretion and sensitivity [ 48 ].…”

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

“…Very recently, hArg administration was shown to inhibit atherogenesis by modulating T cell function (Nitz et al 2022). For a recent review on hArg in health and disease, see (Tsikas 2022). AGAT (Humm et al 1997a, b) and dimethylarginine dimethylaminohydrolase (DDAH; EC 3.5.3.1) (Murray-Rust et al 2001; see also Linsky and Fast 2010;) share very similar catalytic mechanisms.…”

“…AGAT mainly catalyzes the reaction of L-arginine (Arg) with glycine (Gly) to form guanidinoacetate (GAA) and L-ornithine (Orn) (R1) (Scheme 1). AGAT also catalyzes the reaction of Arg with L-lysine (Lys) to form L-homoarginine (hArg) and Orn (R2) (Tsikas and Wu 2015;Tsikas 2022). In these reactions, Arg, hArg and GAA are the amidine (NH 2 -C + = NH) group donors; Gly and Orn are the acceptors of the donated amidine groups via their α-and δ-amine groups, respectively.…”

Mass Spectrometry-Based Evaluation of the Bland–Altman Approach: Review, Discussion, and Proposal

“…L-Homoarginine (hArg) is a non-proteinogenic amino acid. Low plasma and urinary hArg concentrations are considered to be risk markers for cardiovascular and renal diseases [ 87 ]. For the quantitative determination of hArg in human plasma, serum and urine samples, we have developed GC-MS and GC-MS/MS methods using L-[ 2 H 3 ]homoarginine (d 3 -hArg) as the internal standard [ 86 ].…”