The enzyme system that oxygenates 4 alpha-methyl sterols to 4 alpha-carboxylic acids will be studied. A non-heme iron enzyme which is a terminal oxygenase in this process will be characterized. A novel protein will be purified which acts in this reaction to transfer electrons from NADH or NADPH to non-heme iron. Partially purified cytochrome P-450 which demethylates C-32 of lanosterol will be further purified and its mechanisms studied. Blood platelets and other cells synthesize lanosterol from mevalonate, but cannot convert lanosterol to cholesterol. The basis for this block will be explored. Thromboembolic phenomena in women owing to the use of oral contraceptives have been correlated with the accumulation of lanosterol in platelets. C-32 demethylase may therefore be a control point in these and other cells.
