bile acids and poetry
 

Man's liver is a brownish blob
That does a most prodigious job.
It manufactures gall, or bile
And normally keeps some on file
Stored neatly in a pear-shaped sac.
From there the liver's yields attack
The food man eats, to change its state
By methods man can't duplicate,
Or even halfway understand.
He ought to treat this outsize gland,
With due respect and loving care
To keep it in top-notch repair,
Because to get along at all
Man needs an awful lot of gall.

Irene Warsaw, JAMA, 1975, v. 231, p. 1260


Heinrich Otto Wieland

The Nobel Prize in Chemistry 1927

"for his investigations of the constitution of the bile acids and related substances"

Clinically, measurement of serum bile acids can be important to veterinarians as a screening tool for hepatobiliary function. Normally, animals will produce bile acids from cholesterol in their liver and store it in their gall bladder. Bile salts are formed in the hepatocytes by a series of enzymatic steps that convert cholesterol to cholic or chenodeoxycholic acids. The rate limiting step is hydroxylation at the 7-alpha position. These reactions include the activity of 8 enzymes belonging to either monooxygenase or dehydrogenase enzyme classes. These acids are then conjugated with glycine or taurine and secreted as Na+ (or K+) salts. Conjugation causes a decrease in their pKa values, making them more water soluble.


Site of attack of 3-α-hydroxysteroid dehydrogenase used in DCL’s Bile Acids assay for total bile acids

Fast, fast relief from surface tension headaches

When bile acids are conjugated to an amino acid (glycine or taurine) they become amphipathic, they have both hydrophilic and hydrophobic properties and serve as detergents in the gastro intestinal tract to help solubilize dietary fats. As detergents, bile acids act to emulsify fat and reduce the surface tension on fat droplets to prepare them for the action of pancreatic and intestinal fat-splitting enzymes such as lipase.

  • bile acids and phospholipids solubilize cholesterol in the bile, thereby preventing the precipitation of cholesterol in the gall bladder

  • they act as emulsifying agents that render fats accessible to pancreatic lipases

  • they facilitate the intestinal absorption of fat and fat soluble vitamins

The bile acids will then be released into the small intestine via the bile duct during intestinal contraction and play an integral role in the absorption of dietary lipids and lipid soluble vitamins. In most species, more than 90% of the bile salts are actively reabsorbed (by a sodium-dependent co-transport process) from the ileum into the hepatic-portal circulation from where they are cleared and resecreted by the liver to once again be stored in the gall bladder. This secretion/reabsorption cycle is called the Enterohepatic Circulation.



See a full animation of Enterohepatic Circulation

Enterohepatic Recirculation

Large amounts of bile acids are secreted into the intestine every day but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum. Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this Enterohepatic Recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase. It should be noted that liver disease can dramatically alter this pattern of recirculation, for instance, sick hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system can result in escape of bile acids into the systemic circulation. Assays of systemic levels of bile acids such as DCL’s Bile Acids are used clinically as a sensitive indicator of hepatic disease.

Source: Republished with permission by Richard Bowen - Hypertexts for Biomedical Sciences