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Trans effects of Na + and glucose on Na + /glucose co‐transport
Author(s) -
Hummel Charles S.,
Hirayama Bruce A.,
Loo Donald D.F.,
Wright Ernest M.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1014.3
Subject(s) - extracellular , chemistry , cytoplasm , biophysics , transporter , glucose transporter , substrate (aquarium) , sugar , brush border , chromosomal translocation , glucose uptake , biochemistry , crystallography , biology , endocrinology , insulin , membrane , vesicle , gene , ecology
The human intestinal Na + /glucose co‐transporter 1 (SGLT1) is responsible for glucose absorption on the brush border of the small intestine. Previously, it has been shown that two Na + ions bind to the extracellular surface of SGLT1 prior to sugar binding and translocation. However, the order of release on the cytoplasmic surface is not well understood. Molecular dynamics simulations based on the X‐ray crystal structure of a homolog of SGLT1 suggest that Na + is the first substrate to dissociate from the cytoplasmic (i.e. trans ) side of the transporter during a reaction cycle. To test this, we obtained whole cell patch clamp recordings in human SGLT1‐expressing HEK293T cells with varying trans substrate concentrations. Compared with control experiments under zero trans conditions, 85 mM trans glucose reduced the V max for transport by greater than two‐fold. In contrast, trans Na + alone had no effect on V max . These results are consistent with kinetic modeling that predicts sugar is first to dissociate on the cytoplasmic surface of SGLT1. This work was supported by NIH grant #DK19567 and pre‐doctoral fellowship #DK821532 to CSH.