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Pochini L, Scalise M, Galluccio M, et al. Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front Chem. 2014;2:61doi: 10.3389/fchem.2014.00061.
Pochini, L., Scalise, M., Galluccio, M., & Indiveri, C. (2014). Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Frontiers in chemistry, 261. https://doi.org/10.3389/fchem.2014.00061
Pochini, Lorena, et al. "Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health." Frontiers in chemistry vol. 2 (2014): 61. doi: https://doi.org/10.3389/fchem.2014.00061
Pochini L, Scalise M, Galluccio M, Indiveri C. Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front Chem. 2014 Aug 11;2:61. doi: 10.3389/fchem.2014.00061. eCollection 2014. PMID: 25157349; PMCID: PMC4127817.
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Front Chem. 2014 Aug 11;2:61. doi: 10.3389/fchem.2014.00061. eCollection 2014.

Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health.

Frontiers in chemistry

Lorena Pochini, Mariafrancesca Scalise, Michele Galluccio, Cesare Indiveri

Affiliations

  1. Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria Arcavacata di Rende, Italy.

PMID: 25157349 PMCID: PMC4127817 DOI: 10.3389/fchem.2014.00061

Abstract

Glutamine together with glucose is essential for body's homeostasis. It is the most abundant amino acid and is involved in many biosynthetic, regulatory and energy production processes. Several membrane transporters which differ in transport modes, ensure glutamine homeostasis by coordinating its absorption, reabsorption and delivery to tissues. These transporters belong to different protein families, are redundant and ubiquitous. Their classification, originally based on functional properties, has recently been associated with the SLC nomenclature. Function of glutamine transporters is studied in cells over-expressing the transporters or, more recently in proteoliposomes harboring the proteins extracted from animal tissues or over-expressed in microorganisms. The role of the glutamine transporters is linked to their transport modes and coupling with Na(+) and H(+). Most transporters share specificity for other neutral or cationic amino acids. Na(+)-dependent co-transporters efficiently accumulate glutamine while antiporters regulate the pools of glutamine and other amino acids. The most acknowledged glutamine transporters belong to the SLC1, 6, 7, and 38 families. The members involved in the homeostasis are the co-transporters B0AT1 and the SNAT members 1, 2, 3, 5, and 7; the antiporters ASCT2, LAT1 and 2. The last two are associated to the ancillary CD98 protein. Some information on regulation of the glutamine transporters exist, which, however, need to be deepened. No information at all is available on structures, besides some homology models obtained using similar bacterial transporters as templates. Some models of rat and human glutamine transporters highlight very similar structures between the orthologs. Moreover the presence of glycosylation and/or phosphorylation sites located at the extracellular or intracellular faces has been predicted. ASCT2 and LAT1 are over-expressed in several cancers, thus representing potential targets for pharmacological intervention.

Keywords: amino acids; cancer; glutamine; homology models; membrane; nutrients; transporters

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