Cationic amino acid transport through system y+L in erythrocytes of patients with lysinuric protein intolerance

2000 ◽  
Vol 439 (5) ◽  
pp. 513-516 ◽  
Author(s):  
C.A.R. Boyd ◽  
R. Deves ◽  
R. Laynes ◽  
Y Kudo ◽  
G. Sebastio
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Acid Transport ◽  
Lysinuric Protein Intolerance ◽  
Cationic Amino Acid ◽  
Lysinuric Protein ◽  
Protein Intolerance

Lysinuric Protein Intolerance and Hartnup Disease

2016 ◽  
Author(s):  
Gianfranco Sebastio ◽  
Manuel Schiff ◽  
Hélène Ogier de Baulny
Keyword(s):  
Amino Acid ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Basolateral Membrane ◽  
Neurological Involvement ◽  
Lysinuric Protein Intolerance ◽  
Cationic Amino Acid ◽  
Transporter Family ◽  
Lysinuric Protein ◽  
Protein Intolerance

Lysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective cationic amino acid transport at the basolateral membrane of epithelial cells in intestine and kidney. LPI is caused by mutations in the SLC7A7 gene, which encodes the y+LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family. Symptoms usually begin after weaning with refusal of feeding, vomiting, and consequent failure to thrive. Hepatosplenomegaly, hematological anomalies, and neurological involvement including hyperammonemic coma will progressively appear. Lung involvement (specifically pulmonary alveolar proteinosis), chronic renal disease that may lead to end stage renal disease, and hemophagocytic lymphohistiocytosis with macrophage activation all represent complications of LPI that may appear at any time from childhood to adulthood. The great variability of the clinical presentation frequently causes misdiagnosis or delayed diagnosis. The basic therapy of LPI consist of a low-protein diet, low-dose citrulline supplementation, nitrogen-scavenging compounds to prevent hyperammonemia, lysine, and carnitine supplements.

Multiple pathways for cationic amino acid transport in rat thyroid epithelial cell line PC Cl3

2005 ◽  
Vol 288 (2) ◽  
pp. C290-C303 ◽  
Author(s):  
Tiziano Verri ◽  
Cinzia Dimitri ◽  
Sonia Treglia ◽  
Fabio Storelli ◽  
Stefania De Micheli ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Line ◽  
Amino Acid Transport ◽  
Transport Systems ◽  
Residual Fraction ◽  
Acid Transport ◽  
Thyroid Cells ◽  
Cationic Amino Acid ◽  
Rat Thyroid

Information regarding cationic amino acid transport systems in thyroid is limited to Northern blot detection of y+LAT1 mRNA in the mouse. This study investigated cationic amino acid transport in PC cell line clone 3 (PC Cl3 cells), a thyroid follicular cell line derived from a normal Fisher rat retaining many features of normal differentiated follicular thyroid cells. We provide evidence that in PC Cl3 cells plasmalemmal transport of cationic amino acids is Na+ independent and occurs, besides diffusion, with the contribution of high-affinity, carrier-mediated processes. Carrier-mediated transport is via y+, y+L, and b0,+ systems, as assessed by l-arginine uptake and kinetics, inhibition of l-arginine transport by N-ethylmaleimide and neutral amino acids, and l-cystine transport studies. y+L and y+ systems account for the highest transport rate (with y+L > y+) and b0,+ for a residual fraction of the transport. Uptake data correlate to expression of the genes encoding for CAT-1, CAT-2B, 4F2hc, y+LAT1, y+LAT2, rBAT, and b0,+AT, an expression profile that is also shown by the rat thyroid gland. In PC Cl3 cells cationic amino acid uptake is under TSH and/or cAMP control (with transport increasing with increasing TSH concentration), and upregulation of CAT-1, CAT-2B, 4F2hc/y+LAT1, and rBAT/b0,+AT occurs at the mRNA level under TSH stimulation. Our results provide the first description of an expression pattern of cationic amino acid transport systems in thyroid cells. Furthermore, we provide evidence that extracellular l-arginine is a crucial requirement for normal PC Cl3 cell growth and that long-term l-arginine deprivation negatively influences CAT-2B expression, as it correlates to reduction of CAT-2B mRNA levels.

scholarly journals Inducible Slc7a7 Knockout Mouse Model Recapitulates Lysinuric Protein Intolerance Disease

2019 ◽  
Vol 20 (21) ◽  
pp. 5294 ◽  
Author(s):  
Bodoy ◽  
Sotillo ◽  
Espino-Guarch ◽  
Sperandeo ◽  
Ormazabal ◽  
...  
Keyword(s):  
Knockout Mouse ◽  
Failure To Thrive ◽  
Neurological Impairment ◽  
Lysinuric Protein Intolerance ◽  
Metabolic Derangement ◽  
Knockout Mouse Model ◽  
Cationic Amino Acid ◽  
Promising Tool ◽  
Lysinuric Protein ◽  
Protein Intolerance

Lysinuric protein intolerance (LPI) is a rare autosomal disease caused by defective cationic amino acid (CAA) transport due to mutations in SLC7A7, which encodes for the y+LAT1 transporter. LPI patients suffer from a wide variety of symptoms, which range from failure to thrive, hyperammonemia, and nephropathy to pulmonar alveolar proteinosis (PAP), a potentially life-threatening complication. Hyperammonemia is currently prevented by citrulline supplementation. However, the full impact of this treatment is not completely understood. In contrast, there is no defined therapy for the multiple reported complications of LPI, including PAP, for which bronchoalveolar lavages do not prevent progression of the disease. The lack of a viable LPI model prompted us to generate a tamoxifen-inducible Slc7a7 knockout mouse (Slc7a7−/−). The Slc7a7−/− model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of CAA, hypoargininemia and hyperammonemia. Interestingly, the Slc7a7−/− mice also develops PAP and neurological impairment. We observed that citrulline treatment improves the metabolic derangement and survival. On the basis of our findings, the Slc7a7−/− model emerges as a promising tool to further study the complexity of LPI, including its immune-like complications, and to design evidence-based therapies to halt its progression.

scholarly journals Waste Nitrogen Excretion Via Amino Acid Acylation: Benzoate and Phenylacetate in Lysinuric Protein Intolerance

1986 ◽  
Vol 20 (11) ◽  
pp. 1117-1121 ◽  
Author(s):  
Olli Simell ◽  
Ilkka Sipilä ◽  
Jukka Rajantie ◽  
David L Valle ◽  
Saul W Brusilow
Keyword(s):  
Amino Acid ◽  
Nitrogen Excretion ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Protein Intolerance

Apical Transporters for Neutral Amino Acids: Physiology and Pathophysiology

Physiology ◽  
2008 ◽  
Vol 23 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Stefan Bröer
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Molecular Identification ◽  
Molecular Basis ◽  
Amino Acid Transporters ◽  
Lysinuric Protein Intolerance ◽  
Inherited Disorders ◽  
Lysinuric Protein ◽  
Hartnup Disorder ◽  
Protein Intolerance

Absorption of amino acids in kidney and intestine involves a variety of transporters for different groups of amino acids. This is illustrated by inherited disorders of amino acid absorption, such as Hartnup disorder, cystinuria, iminoglycinuria, dicarboxylic aminoaciduria, and lysinuric protein intolerance, affecting separate groups of amino acids. Recent advances in the molecular identification of apical neutral amino acid transporters has shed a light on the molecular basis of Hartnup disorder and iminoglycinuria.

scholarly journals Interactions of y+LAT1 and 4F2hc in the y+l amino acid transporter complex: consequences of lysinuric protein intolerance-causing mutations

2013 ◽  
Vol 32 (04) ◽  
pp. 479-488 ◽  
Author(s):  
Minna Toivonen, ◽  
Maaria Tringham ◽  
Johanna Kurko ◽  
Perttu Terho ◽  
Olli Simell ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transporter ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Acid Transporter ◽  
Protein Intolerance

Lysinuric protein intolerance. Urinary amino acid excretion at 2 and 9 days of age

1994 ◽  
Vol 17 (2) ◽  
pp. 252-253 ◽  
Author(s):  
M. Candito ◽  
C. Vianey-Saban ◽  
J. P. Ferraci ◽  
B. B�bin ◽  
J. P. Chazalette ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Excretion ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Urinary Amino ◽  
Protein Intolerance
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