Liver function Flashcards
Why is cholesterol important?
It is a key component in the synthesis of cell membranes and contributes to the fluidity of membranes (lipid rafts) and is the precursor for the synthesis of several molecules including vitamin D, cortisol, aldoesterone, progesterone, estrogen, testosterone and bile salts.
What are lipid rafts?
Patches of different fluidity in the membrane due to clustering proteins.
How and where is cholesterol synthesised?
80% of the total daily production is in the liver and it is synthesized from Acetyl Co-A.
What are the first main step in cholesterol synthesis?
3-isopentenyl pyrophosphate is formed from mevalonate.
What are the following steps in cholesterol synthesis?
Squalene is synthesised from isopentenyl pyrophosphate and there is cyclization to form lanosterol. Lanosterol eventually then forms cholesterol.
How is cholesterol transported around the body?
As it is a lipophilic molecule and does not dissolve well in aqueous environments, it is packaged with phospholipids and apolipoproteins to form a series of different lipoproteins.
What is the structure of lipoproteins?
They have a lipid core (cholesterol esters and triglycerides) and a hydrophilic outer surface containing phospholipids, free cholesterol and apolipoproteins.
What are the two main different types of lipoproteins?
Low density and high density (LDL and HDLs).
What are the differences in terms of health of these two different lipoproteins?
LDLs are a risk factor for cardiovascular disease wheres HDLs are protective and are seen as healthy.
What is atherosclerosis?
A progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke.
What is associated with the development of atherosclerosis?
Increasing levels of LDL.
How can atherosclerosis be treated?
Inhibitors of cholesterol synthesis such as statins that inhibit HMG CoA reductase in the cholesterol synthesis pathway.
What is the difference between statins and drugs that target the enzyme PCSK9?
Statins regulate the production of cholesterol whereas these other drugs regulate cholesterol directly in the circulation.
Recap: what is the process for bile sale production?
The sphincter of oddi releases bile, bacterial flora modify the primary bile acids which are then released into the GI tract where they are modified by the bacteria.
What does bile contain?
Bile salts, lecithin, HCO3, cholesterol, bile pigments and trace metals.
How is the volume of bile increased?
Epithelial cells lining bile ducts secrete a bicarbonate rich fluid into the bile.
What are the primary bile acids?
Cholic acid and chenodeoxycholic acid.
What are the secondary bile acids?
Deoxycholic and lithocholic.
How are bile salts generated?
Bile acids are conjugated to amino acids to generate water soluble bile salts.
Give an example of a bile salt and how it is formed.
Glycocholate from cholic acid and glycine.
What are bile salts important for?
For the emulsification of fats.
What happens to bile salts once they have entered the liver?
They are recycled back to the liver via the portal vein.
What is enterohepatic circulation?
Recycling of bile salts from the GI tract to the liver.
How are the bile salts recycled?
When they reach the ileum (last segment of the small intestine) they are re-absorbed by a sodium-dependent pathway.
