Download Enterohepatic circulation of bile acids

APPENDICES
I.
THEORY
PRACTICAL LESSON 1
LIPIDS: BIOLOGICAL FUNCTIONS AND CLASSIFICATION.
METABOLIC PATHWAY OF LIPIDS. DIGESTION AND
CATABOLISM
Bile acids and saults
Bile acids are synthesized in the liver by a multistep, multi-organelle
pathway from cholesterol.
Cholic acid and chenodeoxycholic acid are called “primary” bile acids.
Before the bile acids leave the liver, they are conjugated to a molecule of
either glycine or taurine by an amide bond between the carboxyl group of the added
compound. The ratio of glycine to taurine forms in the bile is approximately 3:1.
In the bile they exist as bile salts (sodium or potassium salts of conjugated
bile acids). Bile saults are more effective detergents than bile acids because of their
enhanced amphipathic nature. Bacteria in the intestine can remove glycine and
taurine from bile saults. The deconjugated bile acids are then partly converted to
secondary bile acids by removal of the α- hydroxyl group at position 7. Cholic
acid is converted to deoxycholic acid and chenodeoxycholic acid to lithocholic
acid.
Biological significant of the bile acids
1)They form of pH optimum for lipase:
2)They can be used as emulsifying agent;
3)They can activate phospholipase A2;
4)They can form micelle;
5)They stimulate peristalsis of the gut;
6)They have a bactericidal effect.
Enterohepatic circulation of bile acids
Bile salts secreted into the intestine are efficiently reabsorbed (greater than 95
percent) and reused. The mixture of primary and secondary bile acids and bile salts
is absorbed primarily in the ileum. They are actively transported from the intestinal
mucosal cells into the portal blood, and are efficiently removed by the liver
parenchymal cells. Bile acids are hydrophobic and require a carrier in the portal
blood. Albumin carries them in a noncovalent complex, just as it transport fatty acids
in blood. The liver converts both primary and secondary bile acids into bile salts by
conjugation with glycine or taurine, and secretes them into the bile. The continuous
process of secretion of bile saults into the bile, their passage through the duodenum
where some are converted to bile acids, and their subsequent return to the liver as a
mixture of bile acids and saults is termed the enterohepatic circulation. Between
15 and 30g of bile saults are secreted from the liver into the duodenum each day, yet
only about 0.5g is lost daily in the feces. Approximately 0.5g per day is synthesized
from cholesterol in the liver to replace the lost bile acids.
Metabolism of the chylomicrons
Chylomicrons are assembled in intestinal mucosal cells and carry
triacylglycerol, cholesterol, fat-soluble vitamins and cholesterol esters to the
peripheral tissues. They have only apoprotein B48.
The particle released by the intestinal mucosal cell is called a “nascent”
chylomicron because it is functionally incomplete. When it reaches the plasma, the
particle is rapidly modified, receiving apo E (which is recognized by hepatic
receptors) and apo CII (which is necessary for the activation of lipoprotein lipase, the
enzyme that degrades the TG contained in the chylomicron). The source of these
apolipoproteins is circulating HDL.
Lipoprotein lipase (LPL) is an extra cellular enzyme that is anchored by
heparan sulfate to the capillary walls of the most tissues, but predominantly those
of adipose tissue and cardiac and skeletal muscle. Adult liver does not have this
enzyme. LPL synthesis and transfer to the luminal surface of the capillary is
stimulated by insulin. LPL activated by apo CII on circulating lipoprotein particles
to yield fatty acids and glycerol. The fatty acids are stored (by the adipose tissue)
or used for energy (by the muscle). If they are not immediately taken up by a cell,
the long-chain fatty acids are transported by serum albumin until their uptake does
occur. Glycerol is used by liver (for lipid synthesis, oxidation, gluconeogenesis).
As more than 90 percent of TG in a core of chylomicron is degraded by LPL,
the particle decreases in size and increases in density. The apo C II are returned to
HDLs. The remaining particle, called “remnant”, is rapidly removed from
circulation by the liver, whose cell membranes contain lipoprotein receptors that
recognize apo E. Chylomicron remnants bind to these receptors and are taken into
the hepatocytes by endocytosis. The endocytosed vesicle then fuses with a lysosome,
and the apolipoproteins, cholesteryl esters, and other components of the remnant are
hydrolytically degraded, releasing amino acids, free cholesterol, and fatty acids. The
receptor is recycled.
Patients with deficiency of LPL or apo CII show an accumulation of
chylomicrons in the plasma (type I hyperlipoproteinemia, or familial LPL
deficiency).