Specificity of the imino acid carrier in rat small intestine

Abstract

The rat intestinal imino acid carrier is chloride independent, while in guinea pig and rabbit intestine it is chloride dependent. While non-alpha-amino acids do not significantly interact with guinea pig and rabbit imino acid carriers, inhibition studies had indicated that in rat small intestine beta-alanine, gamma-aminobutyric acid (GABA), and probably taurine might be transported by the imino acid carrier. The present study of rat jejunum demonstrates that the half-maximal activation concentration of beta-alanine (K1/2 beta-Ala) is identical to its inhibition constant (Ki beta-Ala) against GABA, that K1/2GABA is identical to KiGABA against beta-alanine, that proline and sarcosine have identical values of Ki against beta-alanine and GABA, and that Ki of beta-alanine and proline against sarcosine are equal to their K1/2 values. Taurine inhibits the transport of beta-alanine, and 300 mM proline and beta-alanine reduce the transport of taurine measured at 80 mM taurine to the level expected for the diffusive contribution, corresponding to Ki values equal to those against sarcosine. Thus the rat imino acid carrier is the principal carrier of taurine and the only carrier of beta-alanine and GABA. It is also demonstrated that alpha-amino-monocarboxylic acids with side chains in excess of one methyl group do not significantly interact with the imino acid carrier, and the lack of stereospecificity is confirmed.

D‐Cycloserine transport in human intestinal epithelial (Caco‐2) cells: mediation by a H + ‐coupled amino acid transporter

“…In contrast leucine, isoleucine, valine, phenylalanine, methionine, threonine, cysteine, asparagine, glutamine, histidine, arginine, lysine, glutamate and D-aspartate were not effective substrates (Thwaites et at., 1993b,c;1994b;unpublished observa-tions). Many of the amino acid substrates (including proline, fl-alanine, taurine, sarcosine and GABA) accessing the H +-coupled carrier in this human intestinal epithelium are also transported via the Na'-dependent (Cl--independent) Imino carrier characterized in rat small intestine (Munck et at., 1994).…”

“…The main difference in transport via these two transporters is that L-alanine is transported in Caco-2 cells (Thwaites et at., 1994b) but is not transported by the rat Imino carrier (Munck et at., 1994). …”

The molecular basis of neutral aminoacidurias

“…The first is a specific Na + -dependent transporter for proline and hydroxyproline called the IMINO system [61,62], which is encoded by the IMINO or SIT cDNA (SLC6A20) [28,63]. The second is a proton-driven transporter shared by proline and glycine and some other amino acids, such as GABA and b-alanine, which was termed the imino acid carrier [41]. To avoid confusion with the IMINO system, it is now being referred to as the proton-amino acid transporter, encoded by the PAT1 gene (SLC36A1) [1].…”

The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis

“…This proton motive force is also utilized by other nutrient transporters, such as the peptide transporter PEPT1 or the divalent metal ion transporter DMT1 [7,9]. PAT1 is thought to represent the "classic" imino system described in rat intestine [5], supported by the high similarity in its substrate specificity and its only partially Na + -dependent transport activity [12]. The weak dependence on Na + can be explained by the reduced NHE3 activity after the removal of extracellular Na + , leading to a decrease in the transmembrane pH gradient and consequently to a reduced driving force for the H + -coupled PAT1 carrier [5].…”