Abstract
Effect of 1, 1'-decamethylenediguanidine dihydrochloride, phenylhydrazine hydrochloride, 5-nitrosotropolone, 2-(2-aminoethyl)-1'-(p-chlorophenyl) isothiuronium bromide hydrobromide (AEPCIT), vitamin K3, 2-methyl-3, 6-dibromo-1, 4-benzoquinone, ubiquinone-0 (UQ-0), UQ-7, and UQ-9 on the incorporation of mevalonate [2-14C] into cholesterol was examined in the rat liver homogenate. Of the test compounds, 1, 1'-decamethylenediguanidine dihydrochloride, vitamin K3 and 2-methyl-3, 6-dibromo-1, 4-benzoquinone showed a potent inhibitory action, but phenylhydrazine hydrochloride and UQ-0 showed only a slight inhibition. Further, examination was made on the effect of 1, 1'-decamethylenediguanidine dihydrochloride, vitamin K3, and 2-methyl-3, 6-dibromo-1, 4-benzoquinone on the incorporation of mevalonate [2-14C] into total nonsaponifiable lipid and, using a thin-layer chromatogram scanner, changes in the distribution of radioactivity of the intermediates in total nonsaponifiable lipid due to them were examined. In the case of 1, 1'-decamethylenediguanidine dihydrochloride and vitamin K3, only the peak of squalene remained, the peaks of cholesterol and lanosterol disappearing. At the same time they partially inhibited the incorporation of mevalonate [2-14C] into total nonsaponifiable lipid. On the other hand, in the case of 2-methyl-3, 6-dibromo-1, 4-benzoquinone, the peaks of radioactivity were not found, and also the incorporation of mevalonate [2-14C] into total nonsaponifiable lipid was inhibited completely. On the basis of these experiments, the inhibition sites of test compounds on cholesterol biosynthesis were discussed.
