Meta-Biol

• Pathways

Dietary phytosterols (sterols derived from plants) are taken up into enterocytes from the gut lumen. The reaction is thought to be mediated by plasma membrane-associated NPC1L1 protein. Detailed studies in Maden-Darby canine kidney cells, both mediated by endogenous (canine) NPC1L1 and by overexpressed human protein, indicate a major role for NPC1L1 in the uptake of extracellular sterol. These studies have also shown that ezetimibe binds both human and canine proteins and renders them incapable of mediating sterol uptake. The molecular mechanisms of cholesterol transport and ezetimibe inhibition, however, remain unclear (Weinglass et al. 2008).