Substrate cotransport

Wilson, T. H. and Ding, P. Z. (2001). Sodium-substrate cotransport in bacteria, Biochim. Biophys. Acta - Bioenerg., 1505, 121-130. 

Baringhaus KH, Matter H, Stengelin S and Kramer W. Substrate specificity of the ileal and the hepatic Na /bile acid cotransporters of the rabbit. II. A reliable... 

Terada, T., et al. Identification of the histidine residues involved in substrate recognition by a rat H+/ peptide cotransporter, PEPT1. FEES Lett. 1996, 394, 196-200. 

Schroeder, A., et al. Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am. J. Physiol. 1998, 274, G370-G375. 

Kouzuki, H., Suzuki, H., Ito, K., Ohashi, R., Sugiyama, Y., Contribution of sodium taurocholate cotransporting polypeptide to the uptake of its possible substrates into rat hepatocytes, J. Pharmacol. Exp. 

Biegel, A., Gebauer, S., Hartrodt, B., Brandsch, M., Neubert, K and Thondorf, 1. (2005) Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H-E/peptide cotransporter PEPTl.Journal of Medicinal Chemistry, 48, 4410-4419. 

The approach described here can be applied to other cotransporters and antiporters for the development of highly sensitive and selective sensing membranes for substrates (analytes) such as sugars other than D-glucose and amino acids. 

The Na+ gradient established by the (Na+, K+)-ATPase is utilized in the transport of a number of solutes into animal cells via Na-solute cotransport or symport.68 This is well known for glutamate. Renal Na+ cotransport systems for mono- and di-carboxylic acids and for various amino acids have been functionally reconstituted in proteoliposomes. These transport systems are polypeptides solubilized from brush border membranes of renal proximal tubules. The establishment of Na+ gradients (high Na+ outside) resulted in increases in concentrations of substrate inside the proteoliposomes.69... 

Further demonstrations of this sort of counterflow phenomenon for many different substrates in virtually every type of cell have been used as functional hallmarks of carrier-mediated transport. Experimental demonstration of this effect precludes transport being mediated either by simple diffusion or by fixed pores in the membrane. In reviewing 20 years of experimental work related to the carrier hypothesis, LeFevre (1975) lists a number of key functional properties of carrier mediated transport, all of which have stood the test of the subsequent 20 years. These include saturation of transport with increased substrate concentration and associated phenomena such as competition between similar substrates, high rates of unidirectional transport, and countertransport. Also covered are flux coupling (including trans effects and cotransport), chemical specificity, inhibition by protein-specific reagents, hormonal regulation, and a steep dependence of the rate of transport on temperature (included only to bemoan its common inclusion in textbooks ). 

The outer membrane, the plasmalemma, efficiently protects the cell from the environment while, at the same time, carrying out functions important for cell metabolism the uptake of substrates and the elimination of toxic compounds. Substrate exchange with the environment is controlled by transport proteins embedded in the membrane (energy-requiring pumps such as Na+,K+-ATPase, or other transport units such as the Na+/glucose cotransporter and sodium and calcium ion channels) [1],... 

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). 

OCTN2 was identified as an Na+/camitine cotransporter and is also located in the apical membrane of proximal tubular cells. Substrates of OCTN2 are TEA, verapamil, pyrilamine, choline and quinidine (Koepsell et al. 2003). 

It is believed that the major part of inorganic phosphor absorption in the intestine occurs via Na+-dependent phosphate cotransporter NaPi-Iib (SLC34A2, Xu et al. 1999). Small drugs like phosphocarbonic acid and foscamet are transported by this transporter (Swaan et al. 1995 Tsuji and Tamai 1996). However, the substrate range is rather limited including only inorganic phosphate compounds. 

Peptide transporters (PEPT1-2 SLC15A) Proton coupled cotransporters Substrates di- and tripeptides, -lactam antibiotics, valacyclovir, ACE inhibitors, bestatin... 

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