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Review
. 2007 Jul;92(4):603-19.
doi: 10.1113/expphysiol.2005.029959. Epub 2007 Apr 27.

H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine

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Review

H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine

David T Thwaites et al. Exp Physiol. 2007 Jul.

Abstract

The H(+)-electrochemical gradient was originally considered as a driving force for solute transport only across cellular membranes of bacteria, plants and yeast. However, in the mammalian small intestine, a H(+)-electrochemical gradient is present at the epithelial brush-border membrane in the form of an acid microclimate. Over recent years, a large number of H(+)-coupled cotransport mechanisms have been identified at the luminal membrane of the mammalian small intestine. These transporters are responsible for the initial stage in absorption of a remarkable variety of essential and non-essential nutrients and micronutrients, including protein digestion products (di/tripeptides and amino acids), vitamins, short-chain fatty acids and divalent metal ions. Proton-coupled cotransporters expressed at the mammalian small intestinal brush-border membrane include: the di/tripeptide transporter PepT1 (SLC15A1); the proton-coupled amino-acid transporter PAT1 (SLC36A1); the divalent metal transporter DMT1 (SLC11A2); the organic anion transporting polypeptide OATP2B1 (SLC02B1); the monocarboxylate transporter MCT1 (SLC16A1); the proton-coupled folate transporter PCFT (SLC46A1); the sodium-glucose linked cotransporter SGLT1 (SLC5A1); and the excitatory amino acid carrier EAAC1 (SLC1A1). Emerging research demonstrates that the optimal intestinal absorptive capacity of certain H(+)-coupled cotransporters (PepT1 and PAT1) is dependent upon function of the brush-border Na(+)-H(+) exchanger NHE3 (SLC9A3). The high oral bioavailability of a large number of pharmaceutical compounds results, in part, from absorptive transport via the same H(+)-coupled cotransporters. Drugs undergoing H(+)-coupled cotransport across the intestinal brush-border membrane include those used to treat bacterial infections, hypercholesterolaemia, hypertension, hyperglycaemia, viral infections, allergies, epilepsy, schizophrenia, rheumatoid arthritis and cancer.

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Figures

Figure 1
Figure 1
Schematic representation of Na+-coupled solute cotransport (the “Na+ gradient hypothesis”) (A) and the relationship (“functional cooperativity”) between H+-coupled cotransport (via PepT1 or PAT1) and the Na+/H+ exchanger NHE3 (B).
Figure 2
Figure 2
Schematic representation of the H+-coupled nutrient, micronutrient and drug transporters at the brush-border membrane of the mammalian small intestine.

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References

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