Function of ASBT

What does ASBT do?

ASBT is located in the apical membrane of the ileum. Its main function is to transport bile acids, or more specifically, taurocholate molecules, across the membrane, into the portal blood vein. 

How does ASBT do this?

The protein binds two sodium ions, which it absorbs from solution. They help facilitate transport of taurocholate. This is achieved by a conformational change in the protein, from the outward state to the inward state. In the outward facing state, the protein picks up the ions, and taurocholate forms intermolecular bonds with some of the residues in the active site of ASBT. Only one hydrogen bond is formed, the rest of the interactions must simply be Van der Waals forces.

After the substrate binds, the protein goes through a conformational change into the inward facing state. The substrate is then released, and the protein reverts back to its previous shape, ready to transport a new bile acid.

Why does this happen?

Research by Steven A. Weinman proved that the activity of ASBT is driven by electrogenicity; i.e. changes in electrical potential across the membrane cause the protein to change conformation. So ASBT is a voltage gated transporter protein, and its activity is driven by electrical currents in the cells surrounding it.

So why is research into ASBT useful?

An observation studied by Bhat BG, et al, 2003 is that inhibition of ASBT results in reduced cholesterol levels in the blood. ASBT is a pharmaceutical target for drugs capable of lowering cholesterol. Some trials with animals have already proven successful. The long term aim is that a drug helping to treat hypercholesterolemia in humans could be produced. The disease results in heightened risk of heart attacks and strokes, ailments people prefer to avoid.