Gosset Apical sodium-dependent bile acid transporter Overview
The apical sodium-dependent bile acid transporter (ASBT, SLC10A2) is a transmembrane protein responsible for the active reabsorption of bile acids from the terminal ileum. It plays an essential role in the enterohepatic circulation, enabling efficient recycling of bile acids from the intestine to the liver. ASBT is sodium-dependent, functioning as a symporter that uses the sodium gradient to transport bile acids against their concentration gradient. By reclaiming bile acids, ASBT maintains cholesterol and lipid metabolism, supports digestion and absorption of dietary fats and vitamins, and prevents excessive loss of bile acids. Dysregulation or mutations affecting ASBT or related bile acid transporters can cause diverse hepatic, metabolic, or intestinal disorders. ASBT is the pharmacological target for several drugs that modulate bile acid flow and have therapeutic applications in liver disease and chronic constipation.
Mechanism of Action
Inhibition of ASBT/IBAT increases colonic delivery of bile acids, promoting water secretion and reducing pruritus in cholestatic liver disease. Targeting hepatic bile acid transporters (e.g., NTCP) can reduce bile acid uptake into hepatocytes, used experimentally in viral hepatitis therapy. Modulation of enterohepatic circulation to influence cholesterol and lipid absorption.
Biological Functions
Disease Associations
Safety Considerations
- Disruption of bile acid reabsorption can cause diarrhea and fat-soluble vitamin malabsorption
- Inhibition may increase risk of colonic mucosal irritation or exacerbate certain gastrointestinal disorders.
- Genetic deficiency can lead to cholestasis or early liver disease.
Interacting Drugs
Associated Biomarkers
| Biomarker |
|---|
| Serum bile acid levels (as a marker of bile acid reabsorption/transport efficiency) |
| Genetic testing for SLC10A2 mutations |
| Fecal bile acid concentration |