1. L-homoarginine is associated with decreased cardiovascular- and all-cause mortality
Maserame Cleopatra Mokhaneli, Shani Botha-Le Roux, Carla Maria Theresia Fourie, Rainer Böger, Edzard Schwedhelm, Catharina Martha Cornelia Mels Eur J Clin Invest. 2021 May;51(5):e13472. doi: 10.1111/eci.13472. Epub 2020 Dec 24.
Background: Increasing evidence suggests that L-homoarginine, an endogenous analogue of the amino acid L-arginine, may have beneficial effects on vascular homeostasis. We examined whether L-homoarginine is associated with 10-year risk of all-cause and cardiovascular mortality in a black South African population. Methods: We included 669 black South African participants (mean age 59.5 years), 143 of whom died during the 10-year follow-up period. Mortality data were acquired via verbal autopsy. Plasma L-homoarginine (and other related markers) were analysed with liquid chromatography-tandem mass spectrometry. Results: Survivors had higher L-homoarginine levels compared with nonsurvivors (1.25 µM vs. 0.89 µM; P < .001). Multivariable Cox regression analyses revealed that higher plasma L-homoarginine predicted a reduction in 10-year cardiovascular (hazard ratio [HR] per SD increment, 0.61; 95% CI 0.50 to 0.75) and all-cause (hazard ratio [HR] per SD increment, 0.59; 95% CI 0.41 to 0.84) mortality risk. Conclusion: Higher L-homoarginine levels are associated with reduced risk of 10-year cardiovascular and all-cause mortality. Regulation of L-homoarginine levels as a therapeutic target in the management of cardiovascular disease should be investigated.
2. L-homoarginine and cardiovascular disease
Dorothee Atzler, Edzard Schwedhelm, Chi-un Choe Curr Opin Clin Nutr Metab Care. 2015 Jan;18(1):83-8. doi: 10.1097/MCO.0000000000000123.
Purpose of review: An increasing number of reports indicate that low levels of the endogenous amino acid L-homoarginine are linked to cardiovascular disease. In this article, we review the current findings regarding L-homoarginine metabolism and (patho-)physiology with a focus on its clinical impact. Recent findings: Recent clinical and epidemiological studies revealed a strong association of low circulating L-homoarginine with cardiovascular outcomes and mortality. Human and murine studies identified L-arginine:glycine amidinotransferase (AGAT) as the responsible enzyme for endogenous L-homoarginine formation, suggesting a further important function of AGAT apart from its involvement in creatine and energy metabolism. Further studies related L-homoarginine to smoking and hypertension, and metabolic phenotypes. Summary: AGAT deficiency results in diminished intracellular energy stores (i.e., ATP and phosphocreatine), as well as a lack of L-homoarginine, and has been linked to an improved metabolic risk profile, but also to impaired cardiac and cerebrovascular function. L-homoarginine's structural similarity to L-arginine suggested physiological interference with L-arginine pathways (e.g., nitric oxide). Animal experiments and clinical trials are needed to improve knowledge on the physiology of L-homoarginine and differentiate its role as marker and mediator in cardiovascular disease.
3. Possible sources and functions of L-homoarginine in the brain: review of the literature and own findings
Hans-Gert Bernstein, Kristin Jäger, Henrik Dobrowolny, Johann Steiner, Gerburg Keilhoff, Bernhard Bogerts, Gregor Laube Amino Acids. 2015 Sep;47(9):1729-40. doi: 10.1007/s00726-015-1960-y. Epub 2015 Mar 20.
L-Homoarginine is a cationic amino acid derivative, which is structurally related to L-arginine and lysine. Several lines of evidence point to nervous tissue as an important target of homoarginine action. In the mammalian brain homoarginine can be detected in noticeable quantities, but its origin is currently poorly explored. In part I of this review we try to show that both uptake and transport into brain (carried out by cationic amino acid transporters) and local synthesis in the brain (carried out by the homoarginine-synthesizing enzymes L-arginine:glycine amidinotransferase and ornithine transcarbamylse) might contribute to homoarginine brain content. We then give a brief overview about the multiple effects of homoarginine on the healthy brain and show that both homoarginine excess and deficiency are potentially harmful to the central nervous system. In part II, we shortly report about own experiments with regard to the cellular localization of cationic amino acid transporters, as well the enzymes L-arginine:glycine amidinotransferase and ornithine transcarbamylse, in human and rat brains.