The accessory organs: Pancreas, liver and gallbladder
Paul Ong, Rachel Skittrall in Gastrointestinal Nursing, 2017
Bile salts make up one of the most important constituents of bile. They are water-soluble derivatives of cholesterol. Two important bile acids are produced in the liver: cholic acid and chenodeoxycholic acid. These are conjugated (made soluble) to an amino acid to produce the conjugated form that is released into the canaliculi (Figure 6.12). Bile acids perform two important functions. First they help to break down, or emulsify (not digest), fat globules to smaller fat droplets. This helps to increase the surface area across which the enzyme lipase can work to digest fats. When bile salts have completed their function they are released back into the lumen of the small intestine and are transported with chyme to the terminal ileum. The majority of bile acids are reabsorbed across the terminal ileum epithelium into blood and are then transported via the hepatic portal vein to the sinusoids in the liver lobules. Here the bile salts are then taken up by the hepatocytes and are effectively recycled so that they can be secreted again as an important constituent of bile. The continuous recycling of bile acids is known as the enterohepatic circulation (Figure 6.13). In early infancy the secretion of bile salts into the small intestine is much reduced. This has the effect of reducing the digestion of fats, and in particular long-chain fatty acids. This should not present a problem for breastfed infants as breast milk contains fats that are already emulsified.
Steroid Carboxylic Acids
Ronald Hobkirk in Steroid Biochemistry, 1979
Is is probable that all these acids originate from cholesterol after prior modification of the sterol ring. Some are secondary products of microbial action in the gut, which are reabsorbed and modified still further in the liver. The C24 bile acids are by far the major products of cholesterol metabolism and comprise 80 to 90% of the products of cholesterol degradation in humans.61 On the average, a normal human converts about 1000 mg of cholesterol to bile acids each day. Hepatic cholesterol degradation, accompanied by enterohepatic circulation, controls a major proportion of cholesterol metabolism.56,62 Because of the efficient recirculation of bile acids, their half-lives are long. Cholic acid has a half-life of 2.3 days and a pool size of 1.4 g, compared to a total pool of bile acids in man of 3 to 5 g, and an enterohepatic circulation of 20 to 30 g daily.63 The size of the enterohepatic circulation regulates the extent of bile acid formation inversely. The greater the recirculation, the less the production of new bile acids.
Atherosclerosis
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The elimination of cholesterol metabolites takes place entirely through the stool, either as unchanged cholesterol, or bile acids produced in the liver, or coprostanol formed from cholesterol by bacterial action (Figure 13). Small amounts of cholesterol are converted to steroid hormones. The excreted cholesterol mixes with dietary cholesterol and probably limited amounts reenter the pool. Bile acids are reabsorbed efficiently via the enterohepatic circulation into the liver, and only small quantities leave the body (Figure 14). A fraction of cholesterol is excreted through the skin and in the milk during lactation. In the production of bile acids, the conversion of cholesterol to 7α-hydroxycholesterol is the rate-limiting step. The enzyme is located in the microsomal fraction of the hepatocyte and has a short halflife of 2.5 to 3.0 h. Bile salts returning to the liver via the portal circulation exercise a feedback control on 7α-hydroxylase.521,576
Diversification of host bile acids by members of the gut microbiota
Published in Gut Microbes, 2020
Jenessa A. Winston, Casey M. Theriot
High concentrations of conjugated primary bile acids are noted within the duodenum, jejunum, and proximal ileum.13 The primary role of bile acids in the small intestine is to aid in fat emulsification and absorption. Bile acids undergo enterohepatic recirculation, a process which involves: (1). Passive absorption of conjugated and unconjugated bile acids in the small intestine and colon; (2) High-affinity active transport in the distal ileum.1,17,23 Absorbed bile acids enter into the portal bloodstream and are rapidly taken up by hepatocytes and resecreted into bile (Figure 1). A small fraction of bile acids escape enterohepatic recirculation and spill into systemic circulation, which allows bile signaling to occur in other organs and tissues.24,25 Enterohepatic recirculation is extremely efficient, with 95% of bile acids reabsorbed and only 5% lost into the feces.1 Hepatocytes maintain the bile acid pool by synthesizing bile acids to make up for fecal loss. In healthy humans, the total bile acid pool cycles about 10 times each day, which requires enterocytes and hepatocytes to transport about 20 g of bile acids every hour.5,26
Studies of xenobiotic-induced gut microbiota dysbiosis: from correlation to mechanisms
Published in Gut Microbes, 2021
Liang Chi, Pengcheng Tu, Hongyu Ru, Kun Lu
Bile acids are originally synthesized from cholesterol in livers known as primary bile acids, stored in gall bladders and then secreted to small intestines to solubilize lipid and fat-soluble vitamins as potent detergents after a meal. Most of the bile acids can be reabsorbed and backed to our bodies, which is called bile acid enterohepatic circulation. Gut bacteria can hydrolyze the amino acid residues (taurine or glycine) in conjugated bile acids to generate free bile acids. Moreover, some gut bacteria also can synthesize secondary bile acids utilizing primary bile acids.117 Gut bacteria-performed bile acid biotransformation is a critical interaction between the gut microbiota and host, which is not only required to maintain the bile acid homeostasis but also provides key metabolic signaling to multiple tissues in host bodies.118
Insights from pharmacokinetic models of host-microbiome drug metabolism
Published in Gut Microbes, 2020
Maria Zimmermann-Kogadeeva, Michael Zimmermann, Andrew L. Goodman
To this end, we simulated the model for each of the 10,000 random parameter sets with two (low and high) values of either biliary secretion coefficient kEH, or bacterial glucuronidase activity kdglB, and calculated the systemic exposure differences of both drug and drug metabolites between conditions. Enterohepatic circulation most strongly affects drug exposure under conditions that lead to an intact drug in the intestine that can be reabsorbed into circulation (Figure 4b). This is achieved if the drug is readily absorbed from the large intestine, if bacterial glucuronidase activity is high, or if bacterial drug metabolism activity is low. Under the same conditions, systemic metabolite exposure is determined by microbial glucuronidase and host glucuronyl-transferase activity. The propagation coefficient in the large intestine (kp3) also affected systemic metabolite exposure, underlining the importance of intestinal motility in determining host and microbiome contributions to metabolism of enterohepatically cycled drugs. Bacterial glucuronidase activity affected systemic drug levels under the same conditions as enterohepatic circulation, as it directly depends on the latter (Figure 4c).