Na+-to-sugar stoichiometry of SGLT3

Sodium-glucose cotransporters (SGLTs) mediate active transport of sugar acr oss cell membranes coupled to Na+, by using the electrochemical gradient as a driving force. In the kidney, there is evidence for two kinds of cotrans porters, a high-affinity, low-capacity system, and a low-affinity, high-cap acity system, with differences in substrate specificity and kinetics. Three renal SGLT clones have been identified: SGLT1 corresponding to the high-af finity system, and SGLT2 and SGLT3 with properties reminiscent of the low-a ffinity system. We have determined the stoichiometry of pig SGLT3 (pSGLT3) by using a direct method, comparing the substrate-induced inward charge to Na-22 or [C-14]alpha -methyl-D-glucopyranoside uptake in the same oocyte. p SGLT3 stoichiometry is 2 Na+:1 sugar, the same as that for SGLT1, but diffe rent from SGLT2 (1:1). The Na+ Hill coefficient for SGLT3 is similar to1.5, suggesting low cooperativity between Na 1 binding sites. Thus SGLT3 has fu nctional characteristics intermediate between SGLT1 and SGLT2, so, whereas SGLT3 stoichiometry is the same as that for SGLT1 (2:1), sugar affinity and specificity are similar to SGLT2.