Inhibition of Renal Tubular Reabsorption of Hom~cystine by Lysine and Arginine

Asymmetric dimethylarginine in homocystinuria due to cystathionine β‐synthase deficiency: Relevance of renal function

“…The decreased production of nitric oxide is most likely due to inhibition of nitric oxide synthase, but decreased availability of arginine might also contribute. The lower levels of arginine in the patients could be at least partly due to an increase in clearance because of competition with homocysteine at the shared transporter in the proximal renal tubule (Cusworth and Gattereau 1968). All patients were receiving a daily dose of 5 mg of folic acid, which has been reported to lower ADMA levels in healthy subjects with modestly elevated homocysteine levels (Holven et al 2003), but not in several others Sydow et al 2004;Ziegler et al 2005).…”

Reduced urinary excretion of homocysteine could be the reason of elevated plasma homocysteine in patients with psychiatric illnesses

“…Kinetic studies of minced rat renal cortical tissue identified low-Km/high-affinity and high-Km/low-affinity homocystine uptake systems, the former shared with cystine and the dibasic amino acids arginine, ornithine, and lysine [43]. This finding is supported by studies in which rats and human subjects exhibited dramatically increased urinary homocystine excretion after intravenous boluses of arginine and lysine [44] or α-aminoisobutyric acid [45], an inhibitor of lysine, arginine, and ornithine tubular reabsorption.…”

Single amino acid supplementation in aminoacidopathies: a systematic review

“…Arginine has been proposed to be supplemented for two reasons: 1) to decrease endothelial dysfunction [92], and 2) to compete with renal homocysteine reabsorption [93]. Although the exact mechanism of vascular damage in HCU is not well understood, reduced nitrogen oxide (NO) probably plays a central role and increased concentrations of asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, have been found.…”

“…Regarding its second treatment objective, arginine glutamate infusion has been reported to markedly increase urinary homocysteine and homocysteine-cysteine disulphide excretion. However, blood homocysteine concentrations remained unchanged, whereas blood cysteine, lysine, arginine, and ornithine concentrations increased [93]. To conclude, besides the restoration of a cysteine deficiency, cysteine supplementation in HCU patients may have additional effects that should be investigated.…”