SGLT1 - Sodium/Glucose Cotransporter 1 - SLC5A1

Targets and Family: SGLT1 belongs to the Solute:Sodium Symporter Family (SSSF, TCDB: 2.A.21). Since it is a human transporter, it’s also classified as an SLC transporter: SGLT1 equals to SLC5a1 and belongs to the sodium/glucose cotransport family (SLC5).

Function: Absorption of D-glucose in the small intestine using the sodium transmembrane gradient, which is established by the Na⁺/K⁺ ATPase. Na⁺/sugar symport occurs with 2:1 stoichiometry. SGLT1 is known as a high-affinity / low-capacity transporter, having an affinity for its main substrate D-glucose of 0.5 mM and a transport rate of 20 molecules per second.

Organism and Localisation: SGLT1 is a mammalian transporter, localized within the plasma membrane of the small intestine, specifically in the lower segments. Here the high affinity allows for absorption of D-glucose, which was not absorbed by SGLT2. Defects in SGLT1 function can lead to congenital glucose/galactose malabsorption (GGM), an autosomal recessive disorder.

Substrates and Inhibitors: D-glucose is the physiological most relevant substrate. Methyl-D-glucose is often used for experiments on SGLT1, due to the fact that it is not metabolized, but exhibits similar transport properties as D-glucose. Other substrates are galactose; some transport activity was also observed for D-xylose, 2-Desoxy-D-glucose and 3-O-Methyl-D-glucose. Sugar transport is coupled to Na⁺ translocation, but Na⁺ can be replaced by Li⁺ and H⁺. Well-characterized inhibitors are Phlorizin, which has a very high affinity in the nM range for the extracellular site of SGLT1, but very week affinity for the intracellular site. SGLT1 is also inhibited by Phloretin with an IC₅₀ of ~ 100 µM.

Related Transporters: SGLT2 has a different tissue distribution than SGLT1, and is expressed predominantly in the upper segments of the small intestine. It has a higher transport capacity, but lower affinity for D-glucose and a 1:1 Na⁺/D-glucose transport stoichiometry. Other functionally related transporters belong to the GLUT family, which are human D-glucose uniporters or the SWEET family, which contain sugar transporters first found in plants. Highly relevant is also the prototypical and famous bacterial proton-coupled lactose transporter LacY from E.coli.

Data and Applications

SGLT1 - Sugar transport and binding

Icon N1 SURFE²R N1 data and applications:

Short Description: Na⁺/sugar translocation is detected using a sugar concentration jump in presence of sodium. In absence of sodium, we found a pre steady-state signal, representing sugar binding. Under these conditions, no transport is observed.
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SGLT1 - EC50 for D-glucose transport

Icon N1 SURFE²R N1 data and applications:

Short Description: Na+/sugar translocation is detected using a sugar concentration jump in presence of sodium. Here we determined the KM for glucose transport by SGLT1.
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