Flashcards in Cholesterol Deck (46)
What is cholesterol synthesised from?
- all the requirments are supplied by the liver
What are the three main parts of cholesterol biosynthesis?
- Generation of isopentyl pyrophosphate from acetyl-CoA this acts as a building block
- Condensation of six molecules of isopentyl pyrophosphate to form squalene (cytoplasm)
- Cyclisation and demethylation of squalene by monooxygenases to give cholesterol (occurs in ER).
What steroid hormone precursor is derived from cholesterol?
Pregnenolone – gives rise to all 5 types of steroid hormone
What Vitamin is synthesised from cholesterol?
What breakdown products of cholesterol are used as bile salts?
Taurocholate and Glycocholate
Describe the role of cholesterol in signalling.
Cholesterol and sphingolipids form lipid rafts that are involved in localising proteins involved in signalling
What do the phospholipid monolayers of lipoproteins consist of?
What is contained in the core of a lipoprotein?
How are lipoproteins categorised?
Based on density Chylomicrons Very Low Intermediate Low High
Where is lipoprotein lipase found and what does it do?
It is found in capillary endothelial cells
Hydrolyses triacylglycerols to glycerol and fatty acids
Fatty acids are then used in beta-oxidation
What is the role of apoproteins in lipoproteins?
Allows the lipoprotein to be recognised by tissues
What are the clinical features of familial hypercholesterolaemia?
High risk of severe atherosclerosis and coronary infarction in adolescence
What mutation causes FH?
LDLR (LDL receptor)
How do statins reduce the accumulation of cholesterol? Give an example.
Statins are HMG-CoA Reductase inhibitors
Lovastatin – competitively inhibits HMG-CoA Reductase
What do Resins and Sequestrants do?
Hide bile acid-cholesterol complexes and prevents reabsorption by the intestines
Lowers LDL levels
Raises HDL levels
what is cholestrol?
- cholestrol is a steroid
step 1 of biosynthesis of cholestrol?
1. Condensation of 2 acetyl-CoA molecules to form Acetoacetyl CoA.
enzyme = B - ketothiolase
step 2 of biosynthesis of cholestrol?
2. Condensation of another Acetyl-CoA molecule to form HMG-CoA
enzyme = HMG - CoA synthase
step 3 of biosynthesis of cholestrol?
3. HMG-CoA is reduced to generate Mevalonate
enzyme = HMG - CoA reductase
what regulates the activity of HMG - CoA reductase
- bile salts
what happens to the mevalonate?
- undergoes sequential phosphorylation at the hydroxyl groups at positions 3 and 5
- followed by decarboxylation
- to eventually form 3-ISOPENTENYL PYROPHOSPHATE
what happens to the isopentenyl pyrophosphate?
it is isomerised to Dimethylallyl pyrophosphate by Isopentenyl Pyrophosphate Isomerase.
what happens to the Dimethylallyl pyrophosphate?
this condenses with a unit of Isopentenyl pyrophosphate to form geranyl pyrophosphate
what happens to the geranyl pyrophosphate?
Then a third isopentyl pyrophosphate molecule condenses with geranyl pyrophosphate to form
15-carbon Farnesyl Pyrophosphate.
what happens to the Farnesyl Pyrosphosphate ?
-two molecules of the farnesyl pyrophosphate condense to make 30 carbon squalene and 2 molecules of pyrophosphate
what is the first step as squalene gets cyclised to cholesterol?
Squalene is first reduced in the presence of oxygen and NADPH to form squalene epoxide
what is the second step as squalene gets cyclised to cholesterol?
- Squalene epoxide lanosterol-cyclase catalyses the formation of Lanosterol.
what is the third step as squalene gets cyclised to cholesterol?
A series of 1,2-methyl group and hybride shifts along the chain of the squalene molecule result in the formation of four rings.
what is the precursor derived from cholesterol which makes steroid hormones?
- the precursor is pregenolone
- generated by action of enzyme desmolase
- all five classes of steroid hormones come from pregnenolone