Homocitrulline and Homoarginine Synthesis from Lysine

Ryan, Wayne L.; Wells, Ibert C.

doi:10.1126/science.144.3622.1122

Cited by 78 publications

(41 citation statements)

References 8 publications

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“…This may be due to the fact that the kidney is one of the sites for the transaminidation of L-lysine to homoarginine. 21,22 In the LURIC study, homoarginine consistently was found to be low in patients with a low estimated glomerular filtration rate, 23 and hemodialysis patients (4D study) had even lower concentrations. Because homoarginine is synthesized from the amino acid lysine and is suggested to indicate intestinal absorption of exogenous amino acids, 24 it is likely that homoarginine plays a role in the nutritional status of patients.…”

Section: Discussionmentioning

confidence: 99%

Homoarginine, Cardiovascular Risk, and Mortality

et al. 2010

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Background-Homoarginine is an amino acid derivative that may increase nitric oxide availability and enhance endothelial function. The effect of the level of homoarginine on cardiovascular outcome and mortality is unknown. Methods and Results-We assessed cardiovascular and all-cause mortality according to homoarginine levels in a cohort of 3305 subjects referred for coronary angiography from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. After investigating the relation of homoarginine with kidney function and markers of endothelial dysfunction, we explored its effects on adverse outcomes in a second high-risk cohort of 1244 patients with type 2 diabetes mellitus receiving maintenance hemodialysis (4D study [Die Deutsche Diabetes Dialyse Studie]). In the LURIC study, mean serum homoarginine levels were 2.6Ϯ1.1 mol/L. During a median follow-up of 7.7 years, 766 patients died. After adjustments for age and sex, patients in the lowest quartile (Ͻ1.85 mol/L) had a Ͼ4-fold higher rate of dying of cardiovascular disease (hazard ratio 4.1, 95% confidence interval 3.0 to 5.7) than patients in the highest quartile (Ͼ3.1 mol/L). Lower homoarginine levels were associated with lower estimated glomerular filtration rate and higher levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Hemodialysed patients had lower mean homoarginine levels of 1.2Ϯ0.5 mol/L and experienced a 5-fold increased mortality rate compared with LURIC patients (608 deaths during a median follow-up of 4 years). Homoarginine consistently affected mortality, which was 2-fold higher in 4D study patients in the lowest quartile (Ͻ0.87 mol/L) than in patients in the highest quartile (Ͼ1.4 mol/L). Conclusions-Homoarginine levels are independently associated with cardiovascular and all-cause mortality in patients referred for coronary angiography and in patients undergoing hemodialysis. Future studies are needed to elucidate the underlying pathomechanisms. (Circulation. 2010;122:967-975.)

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Section: Discussionmentioning

confidence: 99%

Homoarginine, Cardiovascular Risk, and Mortality

et al. 2010

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“…Elevated plasma a-aminoadipic acid and homoarginine, two metabolites of L-Lys, in group Lys indicated that the rats in group Lys had increased intestinal absorption of L-Lys. [23][24][25] However, the elevation of plasma Lys in group Lys was not statistically significant. As far as we examined, plasma Ala, Pro, Arg, Gln, Asn, homoarginine, and a-aminoadipic acid in group Lys seemed to play some roles in the suppression of vascular calcification.…”

Section: L-ly Protected the Femora From Osteoporotic Changes In Adenimentioning

confidence: 83%

Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Shimomura¹,

Matsui²,

Hamano

et al. 2014

Journal of the American Society of Nephrology

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Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary L-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+L-lysinezHCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. L-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary L-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of L-lysine. Dietary L-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/ phosphate solution. In conclusion, dietary supplementation of L-lysine ameliorated VC by modifying key pathways that exacerbate VC.

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“…Homoarginine is a naturally occurring amino acid derived from lysine, produced mainly in the kidney 31 and found at low concentrations in most bodily fluids. 32,33 Low plasma homoarginine has been associated with decreased renal function, energy metabolism, and NO regulation.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo 31 P magnetic resonance spectroscopy measurements were performed as described previously. 28 At 7-T field strength with the use of a quadrature 31 P coil, spectra were selected from voxels of 160 to 230 µL in the cerebrum of AGAT wild-type (WT; n=5), AGAT −/− (n=4), and AGAT −/− Cr (n=1) mice.…”

Section: Magnetic Resonance Spectroscopy Measurementmentioning

confidence: 99%

“…28 At 7-T field strength with the use of a quadrature 31 P coil, spectra were selected from voxels of 160 to 230 µL in the cerebrum of AGAT wild-type (WT; n=5), AGAT −/− (n=4), and AGAT −/− Cr (n=1) mice. To obtain phosphocreatine/nucleoside triphosphate ratios, the signal intensities of phosphocreatine and nucleoside triphosphate were fitted with the use of Java-based Magnetic Resonance User Interface and corrected for T1 relaxation.…”

Section: Magnetic Resonance Spectroscopy Measurementmentioning

confidence: 99%

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Homoarginine Levels Are Regulated by l -Arginine:Glycine Amidinotransferase and Affect Stroke Outcome

Choe¹,

Atzler²,

Wild³

et al. 2013

Circulation

135

167

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Background— Endogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. Our studies of human cohorts and a confirmatory murine model associated the arginine homologue homoarginine and its metabolism with stroke pathology and outcome. Methods and Results— Increasing homoarginine levels were independently associated with a reduction in all-cause mortality in patients with ischemic stroke (7.4 years of follow-up; hazard ratio for 1-SD homoarginine, 0.79 [95% confidence interval, 0.64–0.96]; P =0.019; n=389). Homoarginine was also independently associated with the National Institutes of Health Stroke Scale+age score and 30-day mortality after ischemic stroke ( P <0.05; n=137). A genome-wide association study revealed that plasma homoarginine was strongly associated with single nucleotide polymorphisms in the l -arginine:glycine amidinotransferase ( AGAT ) gene ( P <2.1×10 −8 ; n=2806), and increased AGAT expression in a cell model was associated with increased homoarginine. Next, we used 2 genetic murine models to investigate the link between plasma homoarginine and outcome after experimental ischemic stroke: (1) an AGAT deletion (AGAT −/− ) and (2) a guanidinoacetate N -methyltransferase deletion (GAMT −/− ) causing AGAT upregulation. As suggested by the genome-wide association study, homoarginine was absent in AGAT −/− mice and increased in GAMT −/− mice. Cerebral damage and neurological deficits in experimental stroke were increased in AGAT −/− mice and attenuated by homoarginine supplementation, whereas infarct size in GAMT −/− mice was decreased compared with controls. Conclusions— Low homoarginine appears to be related to poor outcome after ischemic stroke. Further validation in future trials may lead to therapeutic adjustments of homoarginine metabolism that alleviate stroke and other vascular disorders.

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Homocitrulline and Homoarginine Synthesis from Lysine

Cited by 78 publications

References 8 publications

Homoarginine, Cardiovascular Risk, and Mortality

Homoarginine, Cardiovascular Risk, and Mortality

Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Homoarginine Levels Are Regulated by l -Arginine:Glycine Amidinotransferase and Affect Stroke Outcome

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