Reexamination of the interplay between dibasic amino acids andl-cystine/l-cysteine during tubular reabsorption

1982 ◽  
Vol 395 (3) ◽  
pp. 196-200 ◽  
Author(s):  
Harald V�lkl ◽  
Stefan Silbernagl ◽  
A. Ascher
Keyword(s):  
Amino Acids ◽  
Tubular Reabsorption ◽  
Dibasic Amino Acids

Renal Handling of Dibasic Amino Acids and Cystine in Cystinuria

1977 ◽  
Vol 53 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Tomoaki Kato
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Transport System ◽  
Tubular Reabsorption ◽  
Arginine Infusion ◽  
Amino Acid Infusion ◽  
Control Subjects ◽  
Substrate Concentrations ◽  
Filtered Load ◽  
Dibasic Amino Acids

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 amino 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.

scholarly journals Expression cloning of a human renal cDNA that induces high affinity transport of L-cystine shared with dibasic amino acids in Xenopus oocytes

1993 ◽  
Vol 268 (20) ◽  
pp. 14842-14849
Author(s):  
J. Bertran ◽  
A. Werner ◽  
J. Chillarón ◽  
V. Nunes ◽  
J. Biber ◽  
...  
Keyword(s):  
Amino Acids ◽  
Xenopus Oocytes ◽  
Expression Cloning ◽  
High Affinity ◽  
Dibasic Amino Acids

Experimental Cystinuria: the Cycloleucine Model. I. Amino Acid Interactions in Renal and Intestinal Epithelia

1975 ◽  
Vol 53 (6) ◽  
pp. 1027-1036 ◽  
Author(s):  
André G. Craan ◽  
Michel Bergeron
Keyword(s):  
Amino Acids ◽  
Renal Tubules ◽  
Intestinal Epithelia ◽  
Luminal Membrane ◽  
Luminal Side ◽  
Convoluted Tubules ◽  
Dibasic Amino Acids ◽  
Everted Sacs

The injection of cycloleucine (1-aminocyclopentanecarboxylic acid (ACPC)) into rats produces a hyperexcretion of dibasic amino acids and cystine, an aberration resembling cystinuria. This may constitute a model of experimental cystinuria, and the transport of amino acids involved in this disease was studied with the techniques of everted intestinal sacs (in vitro) and microinjections into renal tubules (in vivo). In everted sacs from normal rats, there was a decrease in transfer and in accumulation of L-cystine (0.03 mM), L-lysine (0.065 mM) and L-valine (0.065 mM) when ACPC was on the mucosal (luminal) side. Dibasic amino acids such as L-ariginine and L-lysine caused a similar inhibition of the transport of L-cystine. However, when ACPC was on the serosal (antiluminal) side, a lesser effect was noted while arginine and lysine had no effect. Intestinal sacs from treated rats (ACPC, 300 mg/kg × 3 days) transferred and accumulated as much L-cystine as those from control rats. The interaction between cycloleucine and L-cystine was competitive at the luminal and non-competitive at the antiluminal side of the intestine. Cycloleucine inhibited L-lysine transport in a non-competitive fashion at either side of the intestine. L-Lysine also interacted in a non-competitive fashion with L-cystine transport at the luminal membrane. In proximal convoluted tubules, the presence of L-arginine or ACPC caused a decrease in the transport of L-cystine and L-lysine. L-Valine exerted no effect. Furthermore, L-lysine and ACPC did not impair the reabsorption of L-valine significantly.These results suggest a functional heterogeneity between luminal and antiluminal membranes of renal and intestinal epithelia and the existence, at both membranes, of different transport sites for cystine and dibasic amino acids.

The synthesis and opioid receptor binding affinities of dermorphin and deltorphin analogs with dibasic amino acids in position 2

1993 ◽  
pp. 455-457
Author(s):  
Andrzej W. Lipkowski ◽  
Aleksandra Misicka ◽  
Jirina Slaninova ◽  
Robert Horvath ◽  
Henry I. Yamamura ◽  
...  
Keyword(s):  
Amino Acids ◽  
Opioid Receptor ◽  
Receptor Binding ◽  
Binding Affinities ◽  
Dibasic Amino Acids ◽  
Opioid Receptor Binding

scholarly journals Cooperation of Antiporter LAT2/CD98hc with Uniporter TAT1 for Renal Reabsorption of Neutral Amino Acids

2018 ◽  
Vol 29 (6) ◽  
pp. 1624-1635 ◽  
Author(s):  
Clara Vilches ◽  
Emilia Boiadjieva-Knöpfel ◽  
Susanna Bodoy ◽  
Simone Camargo ◽  
Miguel López de Heredia ◽  
...  
Keyword(s):  
Amino Acids ◽  
Knockout Mouse ◽  
Functional Relationship ◽  
Tubular Reabsorption ◽  
Compensatory Mechanisms ◽  
Double Knockout ◽  
Knockout Mouse Model ◽  
Relationship Of

Background Reabsorption of amino acids (AAs) across the renal proximal tubule is crucial for intracellular and whole organism AA homeostasis. Although the luminal transport step is well understood, with several diseases caused by dysregulation of this process, the basolateral transport step is not understood. In humans, only cationic aminoaciduria due to malfunction of the basolateral transporter y+LAT1/CD98hc (SLC7A7/SLC3A2), which mediates the export of cationic AAs, has been described. Thus, the physiologic roles of basolateral transporters of neutral AAs, such as the antiporter LAT2/CD98hc (SLC7A8/SLC3A2), a heterodimer that exports most neutral AAs, and the uniporter TAT1 (SLC16A10), which exports only aromatic AAs, remain unclear. Functional cooperation between TAT1 and LAT2/CD98hc has been suggested by in vitro studies but has not been evaluated in vivo.Methods To study the functional relationship of TAT1 and LAT2/CD98hc in vivo, we generated a double-knockout mouse model lacking TAT1 and LAT2, the catalytic subunit of LAT2/CD98hc (dKO LAT2-TAT1 mice).Results Compared with mice lacking only TAT1 or LAT2, dKO LAT2-TAT1 mice lost larger amounts of aromatic and other neutral AAs in their urine due to a tubular reabsorption defect. Notably, dKO mice also displayed decreased tubular reabsorption of cationic AAs and increased expression of y+LAT1/CD98hc.Conclusions The LAT2/CD98hc and TAT1 transporters functionally cooperate in vivo, and y+LAT1/CD98hc may compensate for the loss of LAT2/CD98hc and TAT1, functioning as a neutral AA exporter at the expense of some urinary loss of cationic AAs. Cooperative and compensatory mechanisms of AA transporters may explain the lack of basolateral neutral aminoacidurias in humans.

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