Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Transport of proline and hydroxyproline by the neutral amino-acid exchanger ASCT1.
Pinilla-Tenas J
,
Barber A
,
Lostao MP
.
???displayArticle.abstract??? ASCT1 is a member of the glutamate transporter superfamily cloned from human brain and characterized as a Na(+)-dependent neutral amino-acid exchanger, which displays substrate-induced chloride-channel activity and mediates concentrative transport of alanine. Initial studies in ASCT1-expressing Xenopus laevis oocytes showed that proline did not elicit measurable currents, in contrast to what occurred with alanine, serine or cysteine, suggesting that proline was not an ASCT1 substrate, although it induced the release of alanine from preloaded oocytes. Here, we have studied the uptake of proline and hydroxyproline by ASCT1-expressing oocytes in order to investigate the ability of ASCT1 to translocate these imino acids. The results demonstrate ASCT1-mediated proline transport that is Na(+)-dependent, saturable, inhibited by the reported ASCT1 substrates as well as by hydroxyproline and can drive the imino acid against its concentration gradient. The apparent kinetic constants for the transport of alanine and the imino acids, obtained with oocytes from the same batch, showed maximal transport rate for proline and hydroxyproline to be half of that for alanine. However, K(0.5) for proline was 704 +/- 86 microM, about three times higher than alanine K(0.5) (203.3 +/- 36.4 microM), whereas hydroxyproline K(0.5) was 33.2 +/- 4.3 microM, indicating that the hydroxylation on carbon 4 of proline strongly increases the affinity of ASCT1 for this proline derivative. In summary, the present work demonstrates for the first time the ability of ASCT1 to transport proline and hydroxyproline.
Adams,
Metabolism of proline and the hydroxyprolines.
1980, Pubmed
Adams,
Metabolism of proline and the hydroxyprolines.
1980,
Pubmed
Arriza,
Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family.
1993,
Pubmed
,
Xenbase
Bröer,
The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux.
1999,
Pubmed
,
Xenbase
Christensen,
A distinct Na+-requiring transport system for alanine, serine, cysteine, and similar amino acids.
1967,
Pubmed
Christensen,
Role of amino acid transport and countertransport in nutrition and metabolism.
1990,
Pubmed
Cohen,
Proline-induced potentiation of glutamate transmission.
1997,
Pubmed
Fremeau,
Molecular cloning and expression of a high affinity L-proline transporter expressed in putative glutamatergic pathways of rat brain.
1992,
Pubmed
Kilberg,
Characteristics of system ASC for transport of neutral amino acids in the isolated rat hepatocyte.
1981,
Pubmed
Koser,
Effect of substrate structure on coupling ratio for Na + -dependent transport of amino acids.
1971,
Pubmed
Kruse,
Amino acid transport across the human blood-CSF barrier. An evaluation graph for amino acid concentrations in cerebrospinal fluid.
1985,
Pubmed
Lostao,
Phenylglucosides and the Na+/glucose cotransporter (SGLT1): analysis of interactions.
1994,
Pubmed
,
Xenbase
Malandro,
Molecular biology of mammalian amino acid transporters.
1996,
Pubmed
,
Xenbase
Palacín,
Molecular biology of mammalian plasma membrane amino acid transporters.
1998,
Pubmed
Pinilla,
Active transport of alanine by the neutral amino-acid exchanger ASCT1.
2001,
Pubmed
,
Xenbase
Shafqat,
Cloning and expression of a novel Na(+)-dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters.
1993,
Pubmed
Tamarappoo,
Expressed human hippocampal ASCT1 amino acid transporter exhibits a pH-dependent change in substrate specificity.
1996,
Pubmed
Taylor,
Accumulation of free amino acids in growing Xenopus laevis oocytes.
1987,
Pubmed
,
Xenbase
Thomas,
Indications of spatial relations among structures recognizing amino acids and Na+ at a transport receptor site.
1970,
Pubmed
Velaz-Faircloth,
Mammalian brain-specific L-proline transporter. Neuronal localization of mRNA and enrichment of transporter protein in synaptic plasma membranes.
1995,
Pubmed
Weiss,
Ontogeny and localization of the neutral amino acid transporter ASCT1 in rat brain.
2001,
Pubmed
Wheeler,
Interdependent fluxes of amino acids and sodium ion in the pigeon red blood cell.
1967,
Pubmed
Zafra,
Characteristics and regulation of proline transport in cultured glioblastoma cells.
1994,
Pubmed
Zerangue,
ASCT-1 is a neutral amino acid exchanger with chloride channel activity.
1996,
Pubmed
,
Xenbase