There has been an outstanding debate over the route of cholesterol biosynthesis since it was first discovered in the 1950s. Two alternative pathways have been proposed, the Bloch and Kandutsch-Russell pathways. Using deuterium water labeling coupled to LC-MS/MS we mapped the route that is used in mice and cultured cells.
The cholesterol biosynthesis pathway varied widely between tissues, ranging from almost entirely the Bloch pathway in high-cholesterol biosynthesizing tissues, to mostly a modified version of the Kandutsch-Russell pathway in low-sterol synthesizing tissues. The selective use of these pathways allows for regulation of cholesterol biosynthesis through transcription regulation and mass action.
We continue to study the mechanism for the regulation of this pathway and the physiological effects of disruption.