Renal Handling of Dibasic Amino Acids and Cystine in Cystinuria

Abstract

1. The effect of intravenous infusion of L-lysine and L-arginine on the tubular reabsorption of dibasic amino acids and cystine was studied in normal individuals and in homozygous and heterozygous subjects with cystinuria. 2. The control subjects reabsorbed almost all filtered lysine and arginine until the filtered load was elevated about fourfold. With further increased loads the tubular reabsorption began to fall and tended to approach a maximum reabsorption rate. By contrast, the homozygous subjects could not reabsorb the elevated amino acid beyond the endogenous capacity until the filtered load was increased seven- to ten-fold. When the filtered load was further increased, tubular reabsorption proceeded at the normal rate in the cystinuric patients. 3. These findings may be explained by a low-capacity transport system, which acts at low substrate concentrations, being defective in the cystinuric subjects, while a high-capacity transport system, which predominates at high substrate concentrations, remains intact. 4. Lysine and arginine infusion depressed the percentage tubular reabsorption of other dibasic amino acids and cystine both in the control and the cystinuric subjects. In the control subjects the amino acid infusion caused a gradual linear fall in the fractional reabsorption of the dibasic amino acids and cystine, whereas the depressed reabsorption of the dibasic amono acids in the cystinuric patients returned to that observed under the endogenous condition when the filtered load was high. The amino acid load caused only a gradual decrease in cystine reabsorption in the cystinuric patients. 5. In the heterozygous subjects the slope of the titration curves and the depression of the tubular reabsorption were intermediate between those of the control and homozygous subjects.

Renal transport of lysine and arginine in cystinuria.

“…In the present study the tubular reabsorption of lysine and arginine in the cystinuria patients did not rise as much as that of the control subjects and some of the reabsorption rates gave negative values at low filtered loads, whereas the tubular transport of each amino acid was done at a normal rate with a great increase of the filtered load, showing nearly the same finding as that obtained in the earlier experiments (Kato 1977). An explanation for this might be proposed.…”

“…Dent and Rose (1951) postulated that the dibasic amino acids and cystine have a common transport system which is defective in cystinuria . Lysine or arginine infusion in man (Robson and Rose 1957;Kato 1977) increases the urinary excretion of other dibasic amino acids and cystine , supporting Dent and Rose's hypothesis. However, in vitro studies with renal cortical slices (Rosenberg et al 1962; Fox et al 1964) have shown that the dibasic amino acids have a common transport system that is not shared by cystine .…”

“…The lowconcentration system of the dibasic amino acids would correspond to the low Km system of cystine, and the high-concentration system would separate from the high Km system of cystine. Kato (1977), studying in vivo renal clearance of patients with cystinuria, has postulated a transport defect of the low-concentration system of the dibasic amino acids in cystinuria. Coicadan et al (1980) have suggested a transport defect of lysine in the luminal membrane of the intestinal brush border cell in cystinuria, and Desjeux et al (1980) and Rajantie et al (1980Rajantie et al ( , 1981 have demonstrated a transport defect of the dibasic amino acids in the basolateral membrane of both the gut mucosa and renal tubule in LPI, indicating the location of the defective transport site by the cell membrane.…”

“…exp. Med., 1983, 139 (1), [9][10][11][12][13][14][15][16] To study the defective transport mechanism of cystinuria, renal tubular reabsorption of lysine or arginine in normal and cystinuria subjects was investigated by increasing the filtered load employing intravenous amino acid infusion. In the normal group the amino acid reabsorption rose with increases of the filtered load and reached a maximum (Tm) .…”

Evaluation of Urinary Carnitine and Taurine Excretion in 5 Cystinuric Dogs with Carnitine and Taurine Deficiency

“…Early studies in humans identified 2 transport systems for cystine: a high-Michaelis constant (K m ) system and a low-K m system. 2,3 A defective low-K m system results in excessive amounts of both cystine and dibasic amino acids in urine, whereas a defective high-K m system results only in excessive amounts of cystine in urine. Dibasic aminoaciduria without cystinuria also can occur, and may be due to a defect in a dibasic transport system that is not shared with cystine.…”