Na+-coupled amino acid transport

U Kompella, KJ Kim, MHI Shiue, VHL Lee. (1995). Possible existence of Na+-coupled amino acid transport in the pigmented rabbit conjunctiva. Life Sci 57 1427-1431. 

T. Hatanaka, M. Haramura, Y. J. Fei, S. Miyauchi, C. C. Bridges, P. S. Ganapathy, S. B. Smith, V. Ganapathy, and M. E. Ganapathy. Transport of amino acid-based prodrugs by the Na" - and Cl -coupled amino acid transporter ATB° + and expression of the transporter in tissues amenable for drug delivery. J Pharmacol Exp Ther 308 1138-1147(2004)... 

A putative Na+-coupled amino acid carrier from LLC-PK cells (A system transporter) (Kong et al., 1993) showed a surprising 76% identity and 89% similarity with the amino acid sequence of the Na+-glucose cotransporter from the same cell line (LLC-PKi cells). Transcripts for this transporter were detected in liver, skeletal muscle, and spleen, tissues that do not express high affinity Na+/glu-cose cotransporter. This putative amino acid transporter has now been identified as a low affinity glucose transporter (Mackenzie et al., 1994). 

It is remarkable that a bacterial Na+-coupled proline transporter is more homologous to a mammalian amino acid (or glucose transporter) than are the Na+-depend-ent amino acid transport systems to NaCl-coupled amino acid transporters. The diversity of the ion requirement from a single Na+ to three different ion requirements for transport of some neurotransmitter amines argues for an adaption of a biologically successful mechanism to achieve specialized functions with enhanced sensitivity and selectivity. 

ATB Na+/Cl -coupled broad specificity amino acid transporter B0,+... 

T. Nakanishi, T. Hatanaka, W. Huang, P. D. Prasad, F. H. Leibach, M. E. Ganapathy, and V. Ganapathy. Na+- and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. J. Physiol. 532 297-304 (2001). 

Except for meAIB no other truly specific substrate for an amino acid transport system has been defined. We deliberately chose not to discuss the properties of the putative different systems defined on the basis of selective inhibition. Instead the discussion has focussed on the nature of the ions coupled to amino acid uptake (e.g., Na+, NaCl, etc.), since it now appears from cloning data that the nature of the cotransported ions identifies different families of transporters (see below). 

Turner, R.J. (1986). p amino acid transport across the renal brush-border membrane is coupled to both Na and Cl. J. Biol. Chem. 261,16060-16066. 

SLC38 System A and N, Na -coupled neutral amino acid transporter 6 ... 

Summarizing these results, one has good evidence that at least in Ehrlich cells the accumulative amino acid transport is coupled to an Na flux in the same direction (cotransport) as postulated by the gradient hypothesis, while no hard evidence can be presented for primary active transport of amino acids. 

MRP2 (Fig. 14.6) [34, 63]. In addition, 2 suppresses L-type amino acid transporter 1 and Na /glucose cotransporter 1 transporter s function through the release of their transporters from the apical membranes of Caco-2R cell monolayers. Interestingly, DM-a-CyD augments H -coupled peptide transporter PepTl-mediated uptake of glycylsarcosine in Caco-2 and Caco-2R cell monolayers. 

Amino acids and some small peptides are absorbed into the enterocytes in the jejnnnm. The transport of amino acids from the lumen into the ceU is an active process, coupled to the transport of Na ions down a concentration gradient. There are at least six carrier systems with different amino acid specificities neutral amino acids (i.e. those with no net charge, e.g. branched-chain amino acids) neutral plus basic amino acids imino acids (proline, hydroxyproline) and glycine basic amino acids (e.g. arginine and lysine) P-amino acids and taurine acidic amino acids (glutamic and aspartic acids). 

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