An interstrain difference in cholesterol synthesis in vitro in mice, dependent upon a difference in endogenous NADPH-generating capacity.

Earlier experiments have shown that significantly more endogenously generated NADPH is available for reduction of corticosterone in liver homogenates from C57BL/10 male mice than in those from the DBA/2 strain. To test the effect of this interstrain difference upon a representative NADPH-requiring biosynthetic pathway in vitro, the biosynthesis of cholesterol from mevalonic acid was studied in homogenates of livers from the two strains of mice, with and without addition of an NADPH-generating system. The incorporation of mevalonic acid into cholesterol in homogenates from the C57BL/10 strain is little affected by omission of the NADPH-generating system, but in the DBA/2 strain, addition of an NADPH-generating system is necessary to elevate the level of cholesterol synthesis to that of the C57BL/10 strain. Without this addition, the DBA/2 homogenate mainly produces lanosterol and other precursors of cholesterol which require NADPH for their further metabolism.