Practice question

Sodium-dependent glucose transport exemplifies secondary active symport coupling uphill absorption to downhill sodium entry. SGLT1 gene SLC5A1 located apically in intestinal villus enterocytes and kidney proximal tubule contains fourteen transmembrane helices in LeuT fold forming cavity with two sodium sites Na1 and Na2 plus glucose pocket recognizing hydroxyls. Cycle has ordered binding: two sodium ions bind first increasing affinity for D-glucose by opening outer gate then protein transitions from outward open to occluded to inward open releasing cargo inside. Both substrates move same direction into cell hence symporter opposite of antiport exchanger. Energy for concentrative accumulation up to thousandfold in intestine derives from inward sodium electrochemical gradient established by basolateral Na+/K+ ATPase maintaining low intracellular sodium near twelve millimolar. Stoichiometric coupling allows luminal glucose at low concentration to be concentrated inside important during starvation and renal reabsorption preventing glycosuria and calorie loss. Inhibitors like phlorizin from apple bark block SGLT non-selectively used as scaffold for antidiabetic gliflozins empagliflozin dapagliflozin selectively inhibiting SGLT2 isoform lowering plasma glucose via promoting urinary glucose excretion.