Cholesterol is essential to human health, and its levels are tightly regulated by a balance of synthesis, uptake, Wide Brim Hats and efflux.Cholesterol synthesis requires the actions of more than twenty enzymes to reach the final product, through two alternate pathways.Here we describe a physical and functional interaction between the two terminal enzymes.
24-Dehydrocholesterol reductase (DHCR24) and 7-dehydrocholesterol reductase (DHCR7) coimmunoprecipitate, and when the DHCR24 gene is knocked down by siRNA, DHCR7 activity is also ablated.Conversely, overexpression of DHCR24 enhances DHCR7 activity, but only when a functional form of TRAY DHCR24 is used.DHCR7 is important for both cholesterol and vitamin D synthesis, and we have identified a novel layer of regulation, whereby its activity is controlled by DHCR24.
This suggests the existence of a cholesterol #x201C;metabolon#x201D;, where enzymes from the same metabolic pathway interact with each other to provide a substrate channeling benefit.We predict that other enzymes in cholesterol synthesis may similarly interact, and this should be explored in future studies.