Renal arginine synthesis: studies in vitro and in vivo.

Abstract

Renal arginine synthesis is a major endogenous source of arginine. Argininosuccinate lyase occurs almost exclusively in kidney cortex. In studies with isolated renal cortical tubules, we observed rapid rates of arginine synthesis from citrulline, provided a source of the N atom of the guanidino group of arginine was supplied. Aspartate, glutamate, or glutamine were effective, whereas glycine, alanine, serine, or NH4Cl were ineffective as this second substrate. Arginine synthesis as a function of citrulline concentration was determined and was found to be highly sensitive to citrulline concentrations in the physiological range (60 microM), suggesting that renal arginine synthesis in vivo could be regulated by circulating citrulline levels. Therefore, arginine synthesis by the kidney was investigated in vivo by measuring the net flux of citrulline and arginine in saline-infused (control group) and citrulline-infused rats. In normal animals, uptake of citrulline was 60.5 +/- 20.7 nmol.min-1.100 g body wt-1, and a similar arginine release was observed. Citrulline infusion that increased circulating citrulline levels fourfold resulted in a similar increase in renal citrulline uptake (224 +/- 33 nmol.min-1.100 g-1) and a similar increase in renal production of arginine. The results suggest that the availability of citrulline is a limiting factor for renal arginine synthesis in rats.

Effects ofdl-2-hydroxy-4-methylthiobutyrate on the first-pass intestinal metabolism of dietary methionine and its extra-intestinal availability

“…Thus, the increased portal plasma concentration of citrulline may provide a direct evidence for the increased degradation of glutamate in DL-HMTB-fed piglets. Furthermore, given that the citrulline released by the small intestine is not taken up by the liver, and is utilised for arginine synthesis primarily in the kidneys (23) , the increased citrulline concentration in the arterial plasma may 7·01 0·31 5·46 0·36 7·58 0·56 4·71 0·27 67 5 DL-HMTB 7·01 0·19 5·77 0·37 7·48 0·64 4·95 0·28 71 4 P 0·99 0·21 0·79 0·15 0·26 Table 3. The average concentration (mmol/l) of citrulline, ornithine, taurine and urea in the arterial and portal plasma of piglets fed DL-methionine (DL-MET) or DL-2-hydroxy- also be ascribed to the increased catabolism of glutamate by the intestine.…”

Arginine metabolism: nitric oxide and beyond

“…Thus in most animals the complete pathway for net arginine synthesis outlined in Figure 2 is found only in the small intestine of neonates ; in pigs, however, the complete pathway is also present in weaned animals. In adults, the majority of endogenous arginine synthesis involves an interorgan pathway (also known as the intestinal-renal axis), in which the small intestine releases citrulline into the blood circulation which is then extracted primarily by the kidney for conversion into arginine [50,51]. [52] for infants recovering from persistent pulmonary hypertension.…”

“…in 30 kg pigs [56] and arginine concentration in the pig (69 mg/g of protein) [57]. 6 Data are from Dhanakoti et al [50] for plasma concentrations of citrulline and arginine. Data on endogenous synthesis of arginine from citrulline are from Windmueller and Spaeth [20].…”

“…Analyses of the arginine biosynthetic enzymes in kidney in the 1940s [110,111] paved the way for physiological studies which established the kidney as the major organ involved in endogenous arginine synthesis [50,51]. Approximately 60 % of net arginine synthesis in adult mammals occurs in the kidney [50,60], where citrulline is extracted from the blood and converted stoichiometrically into arginine by the action of ASS and ASL (Figure 2), which are localized within the proximal convoluted tubules [81,[112][113][114][115].…”

“…Approximately 60 % of net arginine synthesis in adult mammals occurs in the kidney [50,60], where citrulline is extracted from the blood and converted stoichiometrically into arginine by the action of ASS and ASL (Figure 2), which are localized within the proximal convoluted tubules [81,[112][113][114][115]. A tight correlation between renal citrulline uptake and renal arginine output has been elegantly demonstrated for both humans and rats [50,116]. Furthermore, in i o rates of arginine synthesis in adult rats are limited primarily by the amount of citrulline produced by other organs, such as the small intestine, rather than by the renal arginine biosynthetic capacity [50].…”