Hepatic cholesterogenesis

Rao, D. R., Chawan, C. B. and Pulusani, S. R. 1981. Influence of milks and S. thermo-philus milk on plasma cholesterol levels and hepatic cholesterogenesis in rats. J. Food Sci. 46, 1339-1341. 

Kato N, Yoshida A. 1980. Effect of dietary PCB on hepatic cholesterogenesis in rats. NutrRepInt 21 107-112. 

Serum cholesterol is usually markedly elevated in biliary obstruction, with especially high values in biliary cirrhosis. A positive correlation is found occasionally (196) but not constantly (193) between the serum bile acid and cholesterol levels. An absence of bile acids in the gut lumen and a reduced cholesterol absorption may stimulate, at least initially, both intestinal and hepatic cholesterol production cf. 92,223), and this in association with a block in elimination both as bile acids and as cholesterol itself rapidly raises the serum cholesterol level. However, in biliary obstruction of long duration, e.g., in biliary cirrhosis, sterol balance studies and urinary bile acid measurement indicate that cholesterol synthesis is markedly reduced (88). In parenchymal cell damage of the liver, the serum cholesterol is normal or decreased, probably because the hepatic cholesterol synthesis, due to cell injury, is reduced in proportion to, or proportionally more than, the decreased cholesterol elimination (11,182) and, furthermore, intestinal and hepatic cholesterogenesis may still be under the partial feedback control of bile acids and absorbed cholesterol, respectively. 

Very recently interest has focused on still earlier control sites in the sterol pathway. According to the important findings of Lane e. al. (3), beta-ketoacyl thiolase and HMG-CoA synthetase occur in the cytoplasm as well as in the mitochondria. A cytoplasmic provision of acetoacetyl-CoA and HMG-CoA would first of all make sterol synthesis autonomous and independent of the mitochondrial supply of these precursors. At the same time HMG-CoA would lose its status as the common intermediate in both keto-genesis and cholesterol synthesis. It seems significant in this context that the citric acid analogue, hydroxycitrate, not only blocks hepatic cholesterogenesis but also inhibits ATP citrate lyase, the enzyme that supplies extramitochondrial acetyl-CoA. 

Sullivan, A.C., Triscari, J. and Miller, O.N. (1974)The influence of (-(-hydroxycitrate on in vivo rates of hepatic glycogenesis and cholesterogenesis. Federal Proceedings 33, 656. 

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