Cholesterol metabolism and vitamin B6. I. Hepatic cholesterogenesis and pyridoxine deficiency

Abstract

Hepatic cholesterogenesis was studied in pair-fed and pyridoxine-deficient rats as well as in rat liver homogenate systems. Crossover of various subcellular components from pair-fed homogenates into pyridoxine-deficient homogenate systems and vice versa was also done.On 8 weeks of pyridoxine deficiency, acetate-14C incorporation rates into liver cholesterol increased by a factor of approximately 10. The same phenomenon was observed with the total liver homogenate systems.Pyridoxine deficiency does not appear to affect HMG-CoA reductase activity of pyridoxine-deficient liver microsomes sufficiently to explain the rapid acetate-1-14C incorporation rates in this same tissue. The activating system(s) responsible for the 10-fold increase in acetate-14C incorporation rates into pyridoxine-deficient rat liver cholesterol appears to be located in the high-speed supernatant fraction. Other subcellular components such as lysosomes and mitochondria are probably implicated to some extent in this phenomenon. The results indicate that vitamin B6 is necessary for normal hepatic cholesterogenesis in the rat.The significance of these findings and the possible relationship between these factors are discussed.