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salts of fatty acids and glycerol.

Most cholesterol turnover takes place in the liver and involves the conversion of cholesterol into soluble and readily excreted bile acids. The synthesis of bile acids is limited to the liver, but several enzymes in the bile acid biosynthetic pathway are expressed in extra-hepatic tissues and there also may contribute to cholesterol turnover. An example of the latter type of enzyme is cholesterol 24-hydroxylase, a cytochrome P450 (CYP46A1) that is expressed at 100-fold higher levels in the brain than in the liver. Cholesterol 24-hydroxylase catalyzes the synthesis of the oxysterol 24(S)-hydroxycholesterol. To assess the relative contribution of the 24-hydroxylation pathway to cholesterol turnover, we performed balance studies in mice lacking the cholesterol 24-hydroxylase gene (Cyp46a1-/- mice). Parameters of hepatic cholesterol and bile acid metabolism in the mutant mice remained unchanged relative to wild type controls. In contrast to the liver, the synthesis of new cholesterol was reduced by ∼40% in the brain, despite steady-state levels of cholesterol being similar in the knockout mice. These data suggest that the synthesis of new cholesterol and the secretion of 24(S)-hydroxycholesterol are closely coupled and that at least 40% of cholesterol turnover in the brain is dependent on the action of cholesterol 24-hydroxylase. We conclude that cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain.

cholesterol, bile acids, and steroid hormones …

Bile salts are secreted at a rate of 24 g/day, but synthesized at a rate of only 0.4 g/day in the average individual. This is because, once bile salts have completed their functions in the biliary tree and intestine, almost all are reabsorbed in the distal ileum and returned to the liver through portal venous circulation. Less than 5% of bile salts are lost in the feces each day, which amounts to about 0.4 g/day. The synthesis of bile salts in the liver is adjusted by the body to match the fecal excretion. Considering that cholesterol is the substrate for bile salt synthesis in the liver, a loss of 0.4 g/day of bile salts translates to a loss of the same quantity of cholesterol (i.e., 0.4 g/day).
p. into bile at the rate of up to 2 g/day. The average diet consists of about 0.4 g/day of cholesterol. Therefore, the amount of cholesterol that is derived from bile in the intestine is up to 5-fold in excess of the amount that is taken in through the diet. The biliary cholesterol and dietary cholesterol are admixed in the intestine to form a pool of cholesterol molecules that are indistinguishable. The average individual absorbs 50% of the cholesterol that passes through the intestine each day. This means that 50% is lost in the feces, amounting to 1.2 g/day.

Start studying cholesterol, bile acids, and steroid hormones

the main organ where de novo synthesis of cholesterol takes place

Lipids are digested and absorbed with the help of bile salts. Products of lipid digestion aggregate to form mixed micelles and are absorbed into the small intestine. Lipids are transported in the form of lipoproteins. Fatty acids are activated, transported across mitochondrial membrane with the help of carnitine transporter. β -oxidation of saturated fatty acids takes place in the mitochondrial matrix. Similarly oxidation of unsaturated and odd chain fatty acids also take place with additional reactions. Ketone bodies are formed in the liver but they are utilized by extra hepatic tissues. In uncontrolled diabetes mellitus and starvation, excessive ketone bodies are formed, leading to ketosis. Fatty acid biosynthesis takes place in the cytosol of cells. Fat gets deposited in the adipose tissue. Acetyl Coenzyme A is the precursor of fatty acid synthesis as well as cholesterol biosynthesis. Elevation of lipids in blood leads to deposition of cholesterol plaques in the arterial walls leading to atherosclerosis. Prostaglandins and leukotrienes are synthesized from twenty carbon unsaturated fatty acids. Phosphatidic acid is an important intermediate in the synthesis of glycerophospholipids. In sphingolipids, sphingosine is present as an alcohol.

AB - Most cholesterol turnover takes place in the liver and involves the conversion of cholesterol into soluble and readily excreted bile acids. The synthesis of bile acids is limited to the liver, but several enzymes in the bile acid biosynthetic pathway are expressed in extra-hepatic tissues and there also may contribute to cholesterol turnover. An example of the latter type of enzyme is cholesterol 24-hydroxylase, a cytochrome P450 (CYP46A1) that is expressed at 100-fold higher levels in the brain than in the liver. Cholesterol 24-hydroxylase catalyzes the synthesis of the oxysterol 24(S)-hydroxycholesterol. To assess the relative contribution of the 24-hydroxylation pathway to cholesterol turnover, we performed balance studies in mice lacking the cholesterol 24-hydroxylase gene (Cyp46a1-/- mice). Parameters of hepatic cholesterol and bile acid metabolism in the mutant mice remained unchanged relative to wild type controls. In contrast to the liver, the synthesis of new cholesterol was reduced by ∼40% in the brain, despite steady-state levels of cholesterol being similar in the knockout mice. These data suggest that the synthesis of new cholesterol and the secretion of 24(S)-hydroxycholesterol are closely coupled and that at least 40% of cholesterol turnover in the brain is dependent on the action of cholesterol 24-hydroxylase. We conclude that cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain.

Most of the enzymes of cholesterol synthesis are ..

2/7/2008 · Where in the cell does cholesterol synthesis take place

N2 - Most cholesterol turnover takes place in the liver and involves the conversion of cholesterol into soluble and readily excreted bile acids. The synthesis of bile acids is limited to the liver, but several enzymes in the bile acid biosynthetic pathway are expressed in extra-hepatic tissues and there also may contribute to cholesterol turnover. An example of the latter type of enzyme is cholesterol 24-hydroxylase, a cytochrome P450 (CYP46A1) that is expressed at 100-fold higher levels in the brain than in the liver. Cholesterol 24-hydroxylase catalyzes the synthesis of the oxysterol 24(S)-hydroxycholesterol. To assess the relative contribution of the 24-hydroxylation pathway to cholesterol turnover, we performed balance studies in mice lacking the cholesterol 24-hydroxylase gene (Cyp46a1-/- mice). Parameters of hepatic cholesterol and bile acid metabolism in the mutant mice remained unchanged relative to wild type controls. In contrast to the liver, the synthesis of new cholesterol was reduced by ∼40% in the brain, despite steady-state levels of cholesterol being similar in the knockout mice. These data suggest that the synthesis of new cholesterol and the secretion of 24(S)-hydroxycholesterol are closely coupled and that at least 40% of cholesterol turnover in the brain is dependent on the action of cholesterol 24-hydroxylase. We conclude that cholesterol 24-hydroxylase constitutes a major tissue-specific pathway for cholesterol turnover in the brain.

Cholesterol: Synthesis, Metabolism, Regulation
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