Details
Bile acid (Breeding) are steroid acids found predominantly in the bile of mammals and other vertebrates. Different molecular forms of Bile acid (Breeding) can be synthesized in the liver by different species. Bile acid (Breeding) are conjugated with taurine or glycine in the liver, and the sodium and potassium salts of these conjugated Bile acid (Breeding) are called bile salts.
Primary Bile acid (Breeding) are those synthesized by the liver. Secondary Bile acid (Breeding) result from bacterial actions in the colon. In humans, taurocholic acid and glycocholic acid (derivatives of cholic acid) and taurochenodeoxycholic acid and glycochenodeoxycholic acid (derivatives of chenodeoxycholic acid) are the major bile salts in bile and are roughly equal in concentration. The conjugated salts of their 7-alpha-dehydroxylated derivatives, deoxycholic acid and lithocholic acid, are also found, with derivatives of cholic, chenodeoxycholic and deoxycholic acids accounting for over 90% of human biliary Bile acid (Breeding).
Bile acid (Breeding) are about 80% of the organic compounds in bile (others are phospholipids and cholesterol). An increased secretion of Bile acid (Breeding) produces an increase in bile flow. The main function of Bile acid (Breeding) is to allow digestion of dietary fats and oils by acting as a surfactant that emulsifies them into micelles, allowing them to be colloidally suspended in the chyme before further processing. They also have hormonal actions throughout the body, particularly through the farnesoid X receptor and GPBAR1 (also known as TGR5).
Production
Bile acid (Breeding) synthesis occurs in liver cells which synthesize primary Bile acid (Breeding) (cholic acid and chenodeoxycholic acid in humans) via cytochrome P450-mediated oxidation of cholesterol in a multi-step process. Approximately 600 mg of bile salts are synthesized daily to replace Bile acid (Breeding) lost in the feces, although, as described below, much larger amounts are secreted, reabsorbed in the gut and recycled. The rate-limiting step in synthesis is the addition of a hydroxyl group of the 7th position of the steroid nucleus by the enzyme cholesterol 7 alpha-hydroxylase. This enzyme is down-regulated by cholic acid, up-regulated by cholesterol and is inhibited by the actions of the ileal hormone FGF15/19.
Prior to secreting any of the Bile acid (Breeding) (primary or secondary, see below), liver cells conjugate them with one of two amino acids, glycine or taurine, to form a total of 8 possible conjugated Bile acid (Breeding). These conjugated Bile acid (Breeding) are often referred to as bile salts because of their physiologically-important acid-base properties. The pKa of the unconjugated Bile acid (Breeding) are between 5 and 6.5, and the pH of the duodenum ranges between 3 and 5, so when unconjugated Bile acid (Breeding) are in the duodenum, they are almost always protonated (HA form), which makes them relatively insoluble in water. Conjugating Bile acid (Breeding) with amino acids lowers the pKa of the bile-acid/amino-acid conjugate to between 1 and 4. Thus conjugated Bile acid (Breeding) are almost always in their deprotonated (A-) form in the duodenum, which makes them much more water-soluble and much more able to fulfil their physiologic function of emulsifying fats.
When these bile salts are secreted into the lumen of the intestine, bacterial partial dehydroxylation and removal of the glycine and taurine groups forms the secondary Bile acid (Breeding), deoxycholic acid and lithocholic acid. Cholic acid is converted into deoxycholic acid and chenodeoxycholic acid into lithocholic acid. All four of these Bile acid (Breeding) can be taken back up into the blood stream, return to the liver, and be re-secreted in a process known as enterohepatic circulation.
Functions
As amphipathic molecules with hydrophobic and hydrophilic regions, conjugated bile salts sit at the lipid/water interface and, at the right concentration, form micelles. The added solubility of conjugated bile salts aids in their function by preventing passive re-absorption in the small intestine. As a result, the concentration of Bile acid (Breeding) (Breeding)/salts in the small intestine is high enough to form micelles and solubilize lipids. "Critical micellar concentration" refers to both an intrinsic property of the Bile acid (Breeding) itself and amount of Bile acid (Breeding) necessary to function in the spontaneous and dynamic formation of micelles. Bile acid-containing micelles aid lipases to digest lipids and bring them near the intestinal brush border membrane, which results in fat absorption.
Synthesis of Bile acid (Breeding) 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 12-18 g of Bile acid (Breeding) into the intestine each day, mostly after meals. The bile acid pool size is between 4–6 g, which means that Bile acid (Breeding) are recycled several times each day. About 95% of Bile acid (Breeding) are reabsorbed by active transport in the ileum and recycled back to the liver for further secretion into the biliary system and gallbladder. This enterohepatic circulation of Bile acid (Breeding) allows a low rate of synthesis but with large amounts being secreted into the intestine.
Bile acid (Breeding) have other functions, including eliminating cholesterol from the body, driving the flow of bile to eliminate certain catabolites (including bilirubin), emulsifying fat-soluble vitamins to enable their absorption, and aiding in motility and the reduction of the bacteria flora found in the small intestine and biliary tract.
Bile acid (Breeding) have metabolic actions in the body resembling those of hormones, acting through two specific receptors, the farnesoid X receptor and G protein-coupled bile acid receptor/TGR5. They bind less specifically to some other receptors and have been reported to regulate the activity of certain enzymes and ion channels and the synthesis of diverse substances including endogenous fatty acid ethanolamides.
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