Opposite Associations of Plasma Homoarginine and Ornithine with Arginine in Healthy Children and Adolescents

Abstract

Homoarginine, a non-proteinogenic amino acid, is formed when lysine replaces ornithine in reactions catalyzed by hepatic urea cycle enzymes or lysine substitutes for glycine as a substrate of renal arginine:glycine amidinotransferase. Decreased circulating homoarginine and elevated ornithine, a downstream product of arginase, predict adverse cardiovascular outcome. Our aim was to investigate correlates of plasma homoarginine and ornithine and their relations with carotid vascular structure in 40 healthy children and adolescents aged 3–18 years without coexistent diseases or subclinical carotid atherosclerosis. Homoarginine, ornithine, arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry with stable isotope-labeled internal standards. Intima-media thickness (IMT) and extra-medial thickness (EMT) of common carotid arteries were estimated by B-mode ultrasound. Homoarginine correlated with arginine (r = 0.43, p = 0.005), age (r = 0.42, p = 0.007) and, weakly, with an increased arginine-to-ornithine ratio, a putative measure of lower arginase activity (r = 0.31, p = 0.048). Ornithine correlated inversely with arginine (r = −0.64, p < 0.001). IMT, EMT or their sum were unrelated to any of the biochemical parameters (p > 0.12). Thus, opposite associations of plasma homoarginine and ornithine with arginine may partially result from possible involvement of arginase, an enzyme controlling homoarginine degradation and ornithine synthesis from arginine. Age-dependency of homoarginine levels can reflect developmental changes in homoarginine metabolism. However, neither homoarginine nor ornithine appears to be associated with carotid vascular structure in healthy children and adolescents.

Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease

“…The second interesting finding of the present study is that the plasma concentrations of hArg and ADMA did not correlate with each other in RA. However, in our RA patients circulating hArg and ADMA correlated with the plasma concentration of Arg, i.e., their common precursor, confirming data reported by other groups for healthy and ill subjects (Jaźwińska-Kozuba et al 2013;Khalil et al 2013;van der Zwan et al 2013). In PAOD and CAD, plasma thCys and ADMA also did not correlate with each other.…”

L-Arginine and SDMA Serum Concentrations Are Associated with Subclinical Atherosclerosis in the Study of Health in Pomerania (SHIP)

“…Specifically, one study reported a significant correlation between ADMA concentration and cIMT in Australian children [ 35 ]. However, this association was not significant for a study conducted in Polish children [ 36 ]. Therefore, whether circulating ADMA levels are a biomarker for atherosclerosis may be dependent upon the geographical location and ethnicity of the population of interest.…”

Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin

“…Interestingly, in another study with 40 healthy children and adolescents, the same median plasma homoarginine concentration was measured as in our controls. An association between intimamedia thickness or extramedial thickness of common carotid arteries and homoarginine could not be found (22). In general, children with T1D however are at high risk of premature, subclinical atherosclerosis which has been confirmed by providing evidence of endothelial dysfunction and increased intimamedia thickness (7,23).…”