Design, Synthesis, and Biological Activity of Novel Triazole Amino Acids Used to Probe Binding Interactions Between Ligand and Neutral Amino Acid Transport Protein SN1.

ChemInform ◽  
2007 ◽  
Vol 38 (48) ◽  
Author(s):  
Mariusz Gajewski ◽  
Ben Seaver ◽  
C. Sean Esslinger
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Transport Protein ◽  
Neutral Amino Acid ◽  
Acid Transport ◽  
Binding Interactions ◽  
Design Synthesis

Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder

2005 ◽  
Vol 33 (1) ◽  
pp. 233-236 ◽  
Author(s):  
S. Bröer ◽  
J.A. Cavanaugh ◽  
J.E.J. Rasko
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Neutral Amino Acid ◽  
Electrophysiological Recording ◽  
Candidate Gene Approach ◽  
Acid Transport ◽  
Japanese Family ◽  
Transporter Family ◽  
Hartnup Disorder

Hartnup disorder is an autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport. A corresponding transport activity has been characterized in kidney and intestinal cells and named system B0. The failure to resorb amino acids in this disorder is thought to be compensated by a protein-rich diet. However, in combination with a poor diet and other factors, more severe symptoms can develop in Hartnup patients, including a photosensitive pellagra-like skin rash, cerebellar ataxia and other neurological symptoms. Homozygosity mapping in a Japanese family and linkage analysis on six Australian pedigrees placed the Hartnup disorder gene at a locus on chromosome 5p15. This fine mapping facilitated a candidate gene approach within the interval, which resulted in the cloning and characterization of a novel member of the sodium-dependent neurotransmitter transporter family (B0AT1, SLC6A19) from mouse and human kidney, which shows all properties of system B0. Flux experiments and electrophysiological recording showed that the transporter is Na+ dependent and Cl− independent, electrogenic and actively transports most neutral amino acids. In situ hybridization showed strong expression in intestinal villi and in the proximal tubule of the kidney. Expression of B0AT1 was restricted to kidney, intestine and skin. A total of ten mutations have been identified in SLC6A19 that co-segregate with disease in the predicted recessive manner, with the majority of affected individuals being compound heterozygotes. These mutations lead to altered neutral amino acid transport function compared to the wild-type allele in vitro. One of the mutations occurs in members of the original Hartnup family described in 1956, thereby defining SLC6A19 as the ‘Hartnup’-gene.

Amino acid transport: microinfusion and micropuncture of Henle's loops and vasa recta

1990 ◽  
Vol 258 (3) ◽  
pp. F504-F513 ◽  
Author(s):  
W. H. Dantzler ◽  
S. Silbernagl
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Systemic Circulation ◽  
Passive Movement ◽  
Neutral Amino Acid ◽  
Acid Transport ◽  
Similar Extent ◽  
Endogenous Amino Acids ◽  
Vasa Recta

Amino acids appear to be reabsorbed distal to the tips of loops of Henle and may be recycled between loops and vasa recta in rat papilla. These possibilities were examined further by microinfusion and micropuncture of loops of Henle and vasa recta. To obtain information on the specificity of amino acid transport distal to the tips of the loops, ascending limbs were continuously microinfused with radioactively labeled L- and D-alanine, L-glutamate, taurine, and mannitol. About 30% of the L- and D-alanine and L-glutamate but none of the taurine or mannitol appeared to be reabsorbed. These results suggest that an acidic and a neutral amino acid are reabsorbed to a similar extent, that reabsorption is not stereospecific, but that it does not occur indiscriminately for all amino acids or for all molecules of similar size. Continuous microinfusion of ascending vasa recta with radioactively labeled L- and D-alanine suggests that amino acids may be able to move from vasa recta into tubules (apparently loops of Henle) without first entering the systemic circulation. However, micropuncture measurements of concentrations of endogenous amino acids in thin ascending limbs and adjacent descending vasa recta do not demonstrate a gradient for passive movement out of loops.

scholarly journals Kinetic parameters of neutral amino acid transport in hybrids between malignant and non-malignant cells

1984 ◽  
Vol 67 (1) ◽  
pp. 63-68
Author(s):  
M.K. White
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Neutral Amino Acid ◽  
Systematic Change ◽  
Acid Transport ◽  
Molecular Change ◽  
L System ◽  
Sodium Dependent ◽  
Kinetics Of

The kinetics of neutral amino acid transport were examined in isogeneic matched pairs of hybrid cells, one member of each pair being tumorigenic, the other not. The L system of transport, which is sodium-independent, was measured by the uptake of leucine, and the A system, which is sodium-dependent, by the uptake of methylaminoisobutyric acid. Although there was variation from one cell type to another in both Km and Vmax for the transport of these amino acids, no systematic change was found to be associated with tumorigenicity. This is in marked contrast with hexose uptake where tumorigenicity was invariably found to be associated with a reduction in Km. It thus appears that whatever molecular change is responsible for the alteration in the kinetics of hexose transport, it is specific, at least to the extent that it does not affect either sodium-dependent or sodium-independent transport of neutral amino acids.

scholarly journals Amino acid sensing by enteroendocrine STC-1 cells: role of the Na+-coupled neutral amino acid transporter 2

2010 ◽  
Vol 298 (6) ◽  
pp. C1401-C1413 ◽  
Author(s):  
Steven H. Young ◽  
Osvaldo Rey ◽  
Catia Sternini ◽  
Enrique Rozengurt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Isobutyric Acid ◽  
Amino Acid Transporter ◽  
Membrane Depolarization ◽  
Neutral Amino Acid ◽  
Acid Transport ◽  
Neutral Amino Acid Transporter ◽  
Acid Transporter

The results presented here show that STC-1 cells, a model of intestinal endocrine cells, respond to a broad range of amino acids, including l-proline, l-serine, l-alanine, l-methionine, l-glycine, l-histidine, and α-methyl-amino-isobutyric acid (MeAIB) with a rapid increase in the intracellular Ca2+ concentration ([Ca2+]i). We sought to identify the mechanism by which amino acids induce Ca2+ signaling in these cells. Several lines of evidence suggest that amino acid transport through the Na+-coupled neutral amino acid transporter 2 (SNAT2) is a major mechanism by which amino acids induced Ca2+ signaling in STC-1 cells: 1) the amino acid efficacy profile for inducing Ca2+ signaling in STC-1 cells closely matches the amino acid specificity of SNAT2; 2) amino acid-induced Ca2+ signaling in STC-1 cells was suppressed by removing Na+ from the medium; 3) the nonmetabolized synthetic substrate of amino acid transport MeAIB produced a marked increase in [Ca2+]i; 4) transfection of small interfering RNA targeting SNAT2 produced a marked decrease in Ca2+ signaling in response to l-proline in STC-1 cells; 5) amino acid-induced increase in [Ca2+]i was associated with membrane depolarization and mediated by Ca2+ influx, since it depended on extracellular Ca2+; 6) the increase in [Ca2+]i in response to l-proline, l-alanine, or MeAIB was abrogated by either nifedipine (1–10 μM) or nitrendipine (1 μM), which block L-type voltage-sensitive Ca2+ channels. We hypothesize that the inward current of Na+ associated with the function of SNAT2 leads to membrane depolarization and activation of voltage-sensitive Ca2+ channels that mediate Ca2+ influx, thereby leading to an increase in the [Ca2+]i in enteroendocrine STC-1 cells.

Brush-border amino acid transport mechanisms in carnivorous eel intestine

1989 ◽  
Vol 257 (3) ◽  
pp. R506-R510 ◽  
Author(s):  
C. Storelli ◽  
S. Vilella ◽  
M. P. Romano ◽  
M. Maffia ◽  
G. Cassano
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brush Border ◽  
Amino Acid Transport ◽  
Membrane Vesicles ◽  
Anguilla Anguilla ◽  
Neutral Amino Acid ◽  
Transport Systems ◽  
European Eel ◽  
Acid Transport

Brush-border membrane vesicles (BBMV) were prepared from European eel (Anguilla anguilla) intestinal epithelium by a magnesium-ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) precipitation technique. Amino acid transport by these purified vesicle preparations was investigated using either radiolabeled substrates or the voltage-sensitive fluorescent dye 3,3'-diethylthiadicarbocyanine iodide [DiSC2(5)]. All amino acids tested exhibited carrier-mediated, Na+-dependent and Na+-independent transfer processes plus diffusion. The only exceptions were glutamic acid and proline, which displayed Na+ dependency and diffusion but did not appear to be transported by Na+-independent agencies. Carrier-mediated transport kinetic constants (Kapp and Jmax) for several amino acids are reported. Cis-inhibition experiments suggested the presence of at least four distinct Na+-dependent transport systems in eel intestinal BBMV: 1) an anionic transport process for glutamic and aspartic acids; 2) a cationic mechanism for lysine and arginine; 3) a relatively specific neutral amino acid carrier for proline and alpha-(methylamino)isobutyric acid; and 4) a nonspecific neutral amino acid system for most other substrates of this group. This scheme for carnivorous fish intestine most closely approximates that reported for mammalian gut with minor dissimilarities that may relate to metabolic differences or specific dietary requirements of the two vertebrate groups.

Sign in / Sign up

Export Citation Format

Share Document