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Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. The body produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis producing 400–600 mg daily. Human adults secrete between 12 and 18 g of bile acids into the intestine each day, mostly after meals.
It is metabolized by the enzyme 7α-hydroxycholest-4-en-3-one 12α-hydroxylase to 7α,12α-dihydroxycholest-4-en-3-one and then to cholic acid, the major primary bile acid in humans. Alternatively, it can be converted into 5β-cholestane-3α,7α-diol and then to chenodeoxycholic acid , the other major primary bile acid in humans.
Cholesterol 7 alpha-hydroxylase is the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7α-hydroxycholesterol. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. [8]
This enzyme is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. This enzyme is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates.
7α-Hydroxycholesterol is a precursor of bile acids, created by cholesterol 7α-hydroxylase (CYP7A1). Its formation is the rate-determining step in bile acid synthesis. [ 1 ]
This is why chenodeoxycholic acid, and not cholic acid, can be used to treat gallstones (because decreasing bile acid synthesis would supersaturate the stones even more). [6] [7] Cholic acid and chenodeoxycholic acid are the most important human bile acids. Other species may synthesize different bile acids as their predominant primary bile ...
These bile acids travel to the gall bladder during the interdigestive phase for storage and to the descending part of the duodenum via the common bile duct through the major duodenal papilla during digestion. 95% of the bile acids which are delivered to the duodenum will be recycled by the enterohepatic circulation.
Between meals, secreted bile is stored in the gall bladder, where 80–90% of the water and electrolytes can be absorbed, leaving the bile acids and cholesterol. [5] During a meal, the smooth muscles in the gallbladder wall contract, causing bile to be secreted into the duodenum to rid the body of waste stored in the bile as well as aid in the ...