Homocitrullinuria and homoargininuria in hyperargininaemia

Abstract

A four-year-old boy with hyperargininaemia had increased urinary excretion of homocitrulline and homoarginine. A single oral lysine load created a marked increase in these amino acids in plasma. A daily oral lysine supplementation resulted in a remarkable urinary leakage of homocitrulline and homoarginine. These findings suggest that the patient had an enhanced synthesis of these amino acids.

Homocitrullinuria and homoargininuria in lysinuric protein intolerance

“…Homoarginine synthesis is thus enhanced when lysine or arginine accumulates as in hyperlysinaemia including saccharopinuria (Carson et al, 1968;Ghadimi, 1978) and in hyperargininaemia (Kato et al, 1988). However, our patient with LPI had high plasma concentration of homoarginine with no accompanying accumulation of either lysine or arginine.…”

“…Homocitrullinuria is observed in hyperlysinaemia (Ghadimi, 1983), saccharopinuria (Carson et al, 1968) and in hype~ornithinaemia, hyperammonaemia and homocitrullinuria (HHH) syndrome (Walser, 1983), citrullinaemia (Walser, 1983 and hyperargininaemia (Kato, et aL, 1988). Lysine is accumulated in the former two diseases and in the latter urea cycl e disorders the accumulation of carbamylphosphate due to retarded conversion 6f ornithine to citrulline may be responsible for the homocitrulline formation.…”

“…In a patient with LPI we observed homocitrullinuria and homoargininuria. These aminoacidurias appear in hyperlysinaemia (Ghadimi, 1978), saccharopinuria (Carson et al, 1968), and in some urea cycle disorders (Walser, 1983;Kato et al, 1988). In LPI, homocitrullinuria has been observed in two sibling patients (Oyanagi et al, 1970), but homoargininuria has not been reported in this disease.…”

L-Homoarginine and L-arginine are antagonistically related to blood pressure in an elderly population

“…4. L-Homoarginine may be synthesized by two metabolic routes, catalyzed by enzymes of the urea cycle [29,30] and L-arginine:glycine amidinotransferase (AGAT) [31][32][33], respectively. AGAT is a key enzyme in the synthesis of creatine [34], but we have recently shown that by substrate promiscuity, it may also play a key role in synthesis of homoarginine in humans [33].…”

Promiscuous activity of arginine:glycine amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine

“…Evidence for in vivo synthesis of homoarginine from lysine was first reported in rats, where 14 C-labeled homoarginine was measured in liver and kidney after injection of 14 C-labeled lysine [16]. In humans, an increase in urinary homoarginine after oral lysine administration has been demonstrated in adults [16] as well as children [17]. The metabolic routes responsible for homoarginine synthesis from lysine in vivo have not yet been unraveled completely.…”