Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2)

Hdl Handle:
http://hdl.handle.net/10675.2/616
Title:
Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2)
Authors:
Ganapathy, Vadivel
Abstract:
The H+-coupled amino acid transporter PAT2 (SLC36A2) transports the amino acids proline, glycine, alanine and hydroxyproline. A physiological role played by PAT2 in amino acid reabsorption in the renal proximal tubule is demonstrated by mutations in SLC36A2 that lead to an iminoglycinuric phenotype (imino acid and glycine uria) in humans. A number of proline, GABA and tryptophan derivatives were examined to determine if they function either as transported substrates or non-transported inhibitors of PAT2. The compounds were investigated following heterologous expression of rat PAT2 in Xenopus laevis oocytes. PAT2 function was characterised by: radiotracer uptake and competition (cis-inhibition) studies; radiotracer efflux and trans-stimulation; and measurement of substrate-induced positive inward current by two-electrode voltage-clamp. In general, the proline derivatives appeared to be transported substrates and the relative ability to induce current flow was closely related to the inhibitory effects on PAT2-mediated; Research Highlights: ⠺PAT2 (SLC36A2) transports proline, glycine, alanine and hydroxyproline. ⠺Heterocyclic proline derivatives are transported substrates. ⠺Heterocyclic GABA derivatives are translocated slowly. ⠺Tryptophan derivatives (e.g. α-methyl-; Abbreviations: 1-ACHC, 1-aminocyclohexanecarboxylic acid; Keywords: PAT2
Citation:
Biochim Biophys Acta. 2011 Jan; 1808(1):260-270
Issue Date:
Jan-2011
URI:
http://hdl.handle.net/10675.2/616
DOI:
10.1016/j.bbamem.2010.07.032
PubMed ID:
20691150
PubMed Central ID:
PMC3000476
Type:
Article
Appears in Collections:
Department of Biochemistry and Molecular Biology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorGanapathy, Vadivelen_US
dc.date.accessioned2012-10-26T16:26:53Z-
dc.date.available2012-10-26T16:26:53Z-
dc.date.issued2011-01en_US
dc.identifier.citationBiochim Biophys Acta. 2011 Jan; 1808(1):260-270en_US
dc.identifier.pmid20691150en_US
dc.identifier.doi10.1016/j.bbamem.2010.07.032en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/616-
dc.description.abstractThe H+-coupled amino acid transporter PAT2 (SLC36A2) transports the amino acids proline, glycine, alanine and hydroxyproline. A physiological role played by PAT2 in amino acid reabsorption in the renal proximal tubule is demonstrated by mutations in SLC36A2 that lead to an iminoglycinuric phenotype (imino acid and glycine uria) in humans. A number of proline, GABA and tryptophan derivatives were examined to determine if they function either as transported substrates or non-transported inhibitors of PAT2. The compounds were investigated following heterologous expression of rat PAT2 in Xenopus laevis oocytes. PAT2 function was characterised by: radiotracer uptake and competition (cis-inhibition) studies; radiotracer efflux and trans-stimulation; and measurement of substrate-induced positive inward current by two-electrode voltage-clamp. In general, the proline derivatives appeared to be transported substrates and the relative ability to induce current flow was closely related to the inhibitory effects on PAT2-mediateden_US
dc.description.abstractResearch Highlights: ⠺PAT2 (SLC36A2) transports proline, glycine, alanine and hydroxyproline. ⠺Heterocyclic proline derivatives are transported substrates. ⠺Heterocyclic GABA derivatives are translocated slowly. ⠺Tryptophan derivatives (e.g. α-methyl-en_US
dc.description.abstractAbbreviations: 1-ACHC, 1-aminocyclohexanecarboxylic aciden_US
dc.description.abstractKeywords: PAT2en_US
dc.rights© 2011 Elsevier B.V.en_US
dc.titleAmino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2)en_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3000476en_US
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biology-

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