Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway

Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7α-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls (P < 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7α-hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls (P < 0.05) and a significant linear correlation (r = 0.771; P < 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7α-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients.—Del Puppo, M., M. Galli Kienle, M. L. Petroni, A. Crosignani, and M. Podda. Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway. J. Lipid Res. 1998. 39: 2477–2482

Catabolism of cholesterol by bovine adrenal-cortex enzymes: in vitro formation of oxygenated sterols and side-chain cleavage products

The identification of sterols and steroids formed by incubation of [7alph-3H, 26-14C]cholesterol with mitochondrial enzymes from bovine adrenal cortex is reported. Only 17% of the radioactivity associated with cholesterol metabolites was found in pregnenolone, whereas 15% was reliable to oxygenated sterols and 6% to steroid compounds. The significance of the formation of these compounds is discussed particularly as regards oxygenated cholesterol derivatives

The effect of cholestyramine on liver HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in various laboratory animals

The activity of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase was assayed in the liver of rats, rabbits, hamsters and guinea pigs at the minimum of the day cycle and after one night fasting. The amount of HMG-CoA reductase, as determined after its complete dephosphorylation in vitro was of the same order of magnitude in the tested species. The dephosphorylated active form of the enzyme was detectable only in the rat. Cholesterol 7 alpha-hydroxylase activity was also much higher in the rat. Cholestyramine treatment stimulated the activity of both enzymes. In particular, the ratio between active and inactive HMG-CoA reductase in rabbits, hamsters and guinea pigs became of the same order of magnitude of that found in rats

Effects of rapeseed oil on fatty acid oxidation and lipid levels in rat heart and liver.

The comparative rates of oxidation of erucic and oleic acids and their CoA esters were studied in heart and liver mitocondria of rats fed a standard diet or semisynthetic diets containing 25% of the calories as either rapesed oil

Chirality of 3 hydroxyoctadecanoic acid from stearoyl CoA by rat liver soluble enzymes

One of the transformation products formed from stearoyl CoA by the soluble enzymes of rat liver homogenate has been identified as 3 hydroxyoctadecanoic acid. The chirality of this acid obtained from incubation of [1 14C]stearoyl CoA with the 105,000 g soluble enzymes of rat liver has been determined. After 10 and 20 min of incubation 70% of the L(+) and 30% of the D(-) enantiomer are formed, whereas racemic 3 hydroxyoctadecanoic acid is isolated after 90 min of incubation. These results suggest either that an epimerizing enzyme is present in the soluble fraction or that 2 enzymes, each specifically forming one of the 2 enantiomers, are present

Evaluation of enzyme activities by gas chromatography-mass spectrometry : HMG-CoA reductase and cholesterol 7\uf061-hydroxylase

Methods are described for the evaluation of HMGCoA reductase and cholesterol 7 alpha-hydroxylase activities. The methods are based on the measurement by selected-ion monitoring of mevalonate, formed from HMGCoA and of 7 alpha-hydroxycholesterol formed from cholesterol, respectively. The methods are as sensitive as those based on the use of radioisotopes but less time-consuming because quantitation is carried out on total lipid extracts. In the case of cholesterol 7 alpha-hydroxylase, the procedure does not require the use of exogenous cholesterol as the substrate, so problems related to its equilibration with endogenous microsomal cholesterol are avoided