Hepatic cholesterol 7a-hydroxylase

Axelson M, Bjorkhem I, Relhner E, Einarsson K. The plasma level of 7a-hydroxy-4-cholesten-3-one reflects the activity of hepatic cholesterol 7a-hydroxylase in man. Febs Lett 1991 284 216-8. 

Sesame oil affects cholesterol mobility in the human organism. To study the potential activity of other kinds of compounds, Hirose et al. [222] analysed the effects of sesamin, a lignan present in the oil, on various aspects of cholesterol metabolism, and they observed that a diet with sesamin reduced the concentration of serum and liver cholesterol except in the group free of cholesterol. Sesamin decreased lymphatic absorption of cholesterol and increased the fecal excretion of the neutral but not the acidic form. At the liver level, there was a significant reduction in the activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase, but the activity of hepatic cholesterol 7a-hydroxylase and alcohol dehydrogenase were not affected. Microscopic histological examination did... 

Kushwaha, R.S. and K.M. Born (1991). Effect of estrogen and progesterone on the hepatic cholesterol 7a-hydroxylase activity in... 

One of the most important enzymes of type A is the hepatic cholesterol 7a-hydroxylase, which catalyzes 7a-hydroxylation of cholesterol [16]. This is the initial and rate-determining reaction in mammalian bile acid biosynthesis. This enzyme is located only in the liver. 

An acetone extract of ginger administered intraduodenally resulted in an increase in bile secretion of rats. In the same study, an aqueous ginger extract had no effects on bile secretion (Yamahara et al. 1985). In rats, ginger has been shown to stimulate hepatic cholesterol 7a-hydroxylase, an enzyme responsible for the conversion of cholesterol to bile acids (Srinivasan and Sambaiah 1991). 

Norlin M, Toll A, Bj6rkhem I, Wikvall K (2000) 24-hydroxycholesterol is a substrate for hepatic cholesterol 7a-hydroxylase (CYP7A). J Lipid Res 41 1629-1639... 

Hypercholesterolemic rats Dietary capsaicin stimulated activity of hepatic cholesterol-7a-hydroxylase [107]... 

Improved methodology for the rapid assay of hepatic HMG-CoA reductase has been described and new and simplified assays are available for cholesterol 7a-hydroxylase, 4-methylsterol oxidase, 3/3-hydroxy-steroid dehydrogen-ase, the biosynthesis of bile acids, and microsomal cholesterol levels.The rate of biosynthesis of gibberellins has been monitored by a bioassay based on /3-amyrin production of Amaranthus seeds. 

Since plasma lipoprotein cholesterol must be the major substrate for bile acid biosynthesis under conditions when the rate of hepatic synthesis of cholesterol is low, regulation of the uptake of lipoprotein cholesterol by the hepatocytes should be of importance not only for the rate of cholesterol synthesis but also for the activity of cholesterol 7a-hydroxylase. It should be mentioned that bile acids are included among the different factors known to be able to modulate the receptor-mediated uptake of cholesterol by the apo-B, E or LDL receptor. The apo-B, E receptor can thus be induced to high levels by treatment with a bile acid sequestrant ]259]. Angelin et al. have shown that preparation of a bile fistula in adult dogs markedly induced the expression of the apo-B, E receptor and that the binding of this receptor could be almost totally abolished by reinfusion of taurocholate [260]. 

Bremer and Gloor [40] concluded that enzymes for both reactions were present in hepatic microsomes, but recent studies with microsomes of rat [40-42] and human liver [43] have confirmed the presence of only one enzyme, CoA ligase. The assay system, essentially that for long-chain acyl-CoA ligase [42,43], includes 50 mM NaF, a phosphate buffer (pH 7.5), the enzyme preparation, and constituents of Eqn. 1. Product formation was linear up to 12 min with added protein (between 0.1 and 1.2 mg) from a crude microsomal fraction. Sterol carrier protein [44], cysteine or nicotinamide [38,40] were without effect. This rate-limiting enzyme in the two-step sequence catalyzing conjugation of bile acids exhibits a diurnal variation such that the time of maximum enzyme activity coincides with predicted maximum activity of cholesterol 7a-hydroxylase and the time of maximal biosynthesis of bile acids [45]. The enzyme has not been purified. 

A. Pinelli, G. Galli, and M. Crestani (2001). The negative effects of bile acids and tumor necrosis factor-a on the transcription of cholesterol 7a-hydroxylase gene (CYP7AI) converge to hepatic nuclear factor-4 A novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors. J. Biol. Chem. 276, 30708-30716. 

Reihner, E., I. Bjbrkhem, B. Angelin, S. Ewerth, and K. Einarsson (1989). Bile acid synthesis in humans Regulation of hepatic microsomal cholesterol 7a-hydroxylase activity. Gastroenterology 97, 1498-1505. 

The possible mechanism of action of capsaicinoids is the net effect of decreased cholesterol absorption and increased excretion of cholesterol and bile acids in the feces which may lead to a decrease in plasma LDL-cholesterol concentration by induced expression of hepatic LDL receptors [110]. These authors also have discussed the differences in response between normal and cholesterol-fed animals to possible hypocholesterolemic compounds. It has been demonstrated that dietary capsaicin stimulates hepatic conversion of cholesterol to bile acids through a stimulation of the activity of cholesterol-7a-hydroxylase, an important pathway... 

Babu PS, Srinivasan K (1997) Influence of dietary capsaicin and onion on the metabolic abnormalities associated with diabetes mellitus. Mol Cell Biochem 175 49-57 Srinivasan K, Sambaiah K (1991) Effect of spices on cholesterol-7a-hydroxylase activity and on serum and hepatic cholesterol levels in the rat. Int J Vitam Nutr Res 61 364—369 Negulesco JA, Young RM, Ki P (1983) Capsaicin lowers plasma cholesterol and triglycerides of lagomorphs. Artery 12 301-311... 

Bile acids are formed from cholesterol in the liver via a sequence of reactions initiated by 7a-hydroxylase. Two primary bile acids, cholic acid and chenodeoxycholic acid, are formed and secreted as glycine or taurine conjugates into the bile and intestine. Most of them are reabsorbed, taken up by the liver and resecreted, completing enterohepatic circulation of bile salts. During each cycle a small amount of bile acids escape into the colon and feces and is regenerated by new hepatic synthesis. 

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