Sterol carrier protein hypothesis: Requirement for three substrate-specific soluble proteins in liver cholesterol biosynthesis

The 105,000 x g supernatant (S 105) of liver is required for the conversion of squalene to cholesterol by microsomal membranes. Substantial controversy has existed concerning the properties of what was originally considered to be a single sterol carrier protein present in S 105 and required for this conversion. We have now resolved this controversy by the discovery that S 105 contains several sterol carrier proteins. Based upon experiments with three substrates, three substrate-specific soluble proteins (with different properties) have been identified which operate at distinct points in microsomal cholesterol synthesis. These proteins are provisionally designated sterol carrier protein 1 (SCP 1), sterol carrier protein 2 (SCP 2), and sterol carrier protein 3 (SCP 3). SCP 1 is required for the microsomal conversion of squalene to lanosterol, SCP 2 for the microsomal conversion of 4,4-dimethyl-Δ 8-cholesterol to C 27-sterols, and SCP 3 for the microsomal conversion of 7-dehydrocholesterol to cholesterol. Available evidence is consistent with the proposal that a given sterol carrier protein is a soluble constituent of a single microsomal enzyme or enzyme complex, and that it participates both as a carrier for the water-insoluble substrate and as an essential enzyme constituent facilitating catalysis. It may well be that enzymatic transformations of water-insoluble substrates require both microsomal membranes and substrate-specific soluble proteins. This requirement could be a common biological mechanism for water-insoluble substrates.