The Inhibition of Sterol Biosynthesis in Rat Liver Homogenates by Bile

From the ¹ From the Department of Physiological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The incorporation in vitro of acetate-1-¹⁴C into digitonin-precipitable sterols in rat liver homogenates is markedly inhibited by small amounts of rat bile. The incorporation in vitro of mevalonate-2-¹⁴C into digitonin-precipitable sterols in the same enzyme system is much less sensitive to bile, suggesting that the major site of action of bile in suppressing sterol biosynthesis from acetate is at a pre-mevalonate step in the biosynthetic pathway. Fasting, which is known to suppress the rate of hepatic cholesterol biosynthesis from acetate in the rat, results in a 2-fold increase in the inhibitory activity of bile. A major part of the inhibitory activity appears to be associated with the protein fraction of bile. This inhibitory protein fraction of bile has been partially purified and characterized. An approximate molecular weight of 19,000 has been determined for the inhibitory protein from the results of gel filtration and sucrose density gradient centrifugation experiments.

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