Cholesterol Is Excreted From The Body In The Bile As Cholesterol Or Bile Acids Salts

About 1 g of cholesterol is eliminated from the body per day. Approximately half is excreted in the feces after conversion to bile acids. The remainder is excreted as cholesterol. Coprostanol is the principal sterol in the feces; it is formed from cholesterol by the bacteria in the lower intestine.

Bile Acids Are Formed From Cholesterol

The primary bile acids are synthesized in the liver from cholesterol. These are cholic acid (found in the largest amount) and chenodeoxycholic acid (Figure 26-7).

(secondary bile acid) (secondary bile acid)

Figure 26-7. Biosynthesis and degradation of bile acids. A second pathway in mitochondria involves hy-droxylation of cholesterol by sterol 27-hydroxylase. Asterisk: Catalyzed by microbial enzymes.

(secondary bile acid) (secondary bile acid)

Figure 26-7. Biosynthesis and degradation of bile acids. A second pathway in mitochondria involves hy-droxylation of cholesterol by sterol 27-hydroxylase. Asterisk: Catalyzed by microbial enzymes.

The 7a-hydroxylation of cholesterol is the first and principal regulatory step in the biosynthesis of bile acids catalyzed by 7a-hydroxylase, a microsomal enzyme. A typical mono oxygenase, it requires oxygen, NADPH, and cytochrome P450. Subsequent hydroxylation steps are also catalyzed by monooxygenases. The pathway of bile acid biosynthesis divides early into one subpathway leading to cholyl-CoA, characterized by an extra a-OH group on position 12, and another pathway leading to chenodeoxycholyl-CoA (Figure 26-7). A second pathway in mitochondria involving the 27-hydroxylation of cholesterol by sterol 27-hydroxylase as the first step is responsible for a significant proportion of the primary bile acids synthesized. The primary bile acids (Figure 26-7) enter the bile as glycine or taurine conjugates. Conjugation takes place in peroxisomes. In humans, the ratio of the glycine to the taurine conjugates is normally 3:1. In the alkaline bile, the bile acids and their conju gates are assumed to be in a salt form—hence the term "bile salts."

A portion of the primary bile acids in the intestine is subjected to further changes by the activity of the intestinal bacteria. These include deconjugation and 7a-dehydroxylation, which produce the secondary bile acids, deoxycholic acid and lithocholic acid.

Most Bile Acids Return to the Liver in the Enterohepatic Circulation

Although products of fat digestion, including cholesterol, are absorbed in the first 100 cm of small intestine, the primary and secondary bile acids are absorbed almost exclusively in the ileum, and 98-99% are returned to the liver via the portal circulation. This is known as the enterohepatic circulation (Figure 26-6). However, lithocholic acid, because of its insolubility, is not reabsorbed to any significant extent. Only a small fraction of the bile salts escapes absorption and is therefore eliminated in the feces. Nonetheless, this represents a major pathway for the elimination of cholesterol. Each day the small pool of bile acids (about 3-5 g) is cycled through the intestine six to ten times and an amount of bile acid equivalent to that lost in the feces is synthesized from cholesterol, so that a pool of bile acids of constant size is maintained. This is accomplished by a system of feedback controls.

Bile Acid Synthesis Is Regulated at the 7 «-Hydroxylase Step

The principal rate-limiting step in the biosynthesis of bile acids is at the cholesterol 7a-hydroxylase reaction (Figure 26-7). The activity of the enzyme is feedback-regulated via the nuclear bile acid-binding receptor farnesoid X receptor (FXR). When the size of the bile acid pool in the enterohepatic circulation increases, FXR is activated and transcription of the cholesterol 7a-hydroxylase gene is suppressed. Chenodeoxycholic acid is particularly important in activating FXR. Cholesterol 7a-hydroxylase activity is also enhanced by cholesterol of endogenous and dietary origin and regulated by insulin, glucagon, glucocorticoids, and thyroid hormone.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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