7 Cholesterol Flashcards
Q: What is cholesterol and what is its role? depending on? (2) changes?
A: steroid hormone
affects membrane stiffness depending on temperature and membrane type
changes interactions with the cytoskeleton
Q: What are the 4 parts of cholesterol synthesis?
A: synthesis of mevalonate from 3 acetyl CoA units
Activation of mevalonate to isopentenyl pyrophosphate (activated isoprene unit) in cytoplasm
Condensation of 6 molecules of isopentyl pyrophosphate = squalene (in cytoplasm)
Cyclisation and demethylation of squalene
E: monooxygenases = cholesterol (in ER)
Q: Describe step 1 of cholesterol synthesis. (2)
A: 3 acetyl-CoA-> 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
E: HMG-CoA synthase
HMG-CoA -> mevalonate
E: HMG-CoA reductase
(End product inhibition)
Q: Describe step 3 of cholesterol synthesis. (4)
A: isopentenyl pyrophosphate is isomerised to form dimethyl pyrophosphate,
Condenses with another unit of isopentenyl pyrophosphate -> geranyl pyrophosphate
Condenses with another unit of isopentenyl pyrophosphate -> 15C farnesyl pyrophosphate
2 farnesyl pyrophosphate — condense —> 30C squalene + 2 pyrophosphate molecules
(reaction driven by reducing power of NADPH)
Q: Describe step 4 of cholesterol synthesis. (3)
A: squalene is cyclised to cholesterol in 3 steps
Squalene-> squalene epoxide
E: squalene monoxygenase = reduction
Squalene epoxide -> lanosterol
Lanosterol = reduced and 3 methyl units removed (demethylated) -> cholesterol
Q: What is cholesterol the basis of?
A: steroid hormones
Q: What are the 5 classes of steroid hormones? And what is their precursor?
A: precursor is pregnenolone which is generated from cholesterol, E: desmolase
Cholesterol (C27)
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Prognenolone (C21)
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PROGESTAGENS (C21)
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GLUCOCORTICOIDS (C21)
+ MINERALOCORTICOIDS (C21)
+ ANDROGENS (C19)
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ESTROGENS (C18)
Q: What is bile? Summarise the synthesis of bile acids.
A: bile salts are major breakdown products of cholesterol
Cholesterol is converted by a series of reactions to primary bile salts GLYCOCHOLATE + TAUROCHOLATE
Q: Explain the mechanism of transport of cholesterol around the body.
A: forms lipoproteins to overcome (packaged within) transportation issue of lipids being insoluble in aqueous solutions
Q: What occurs when bile salts form mixed micelles?
A: hydrophobic tails in towards triacylglycerols TAGs
Q: What are lipid rafts? Role?
A: fluctuating assemblies of cholesterol and sphingolipids that organise processes eg. cell signalling
They localise key proteins such as the cell surface receptors
Q: What do lipoproteins consist of? (4)
A: Phospholipid monolayer - unesterified cholesterol and apoproteins
Core of cholesteryl esters and triacylglycerols
Q: What is the role of apoproteins? Different cells?
A: allow recognition of particle (lipoprotein) by tissues
The different types have varying apoproteins content which allows recognition by different cell types
Q: How are cholesterol esters synthesised? (2) ACAT? What’s their purpose?
A: in plasma from cholesterol and acyl chain of phosphatidycholine (lecithin)
E: lecithin cholesterol acyltransferase LCAT
Or [acyl CoA cholesterol acyltransferase] ACAT can generate cholesterol esters from long chain fatty acyl CoA species where ACAT is intracellular E and acts on cholesterol taken up by endocytosis
Makes cholesterol esters more hydrophobic= pack more tightly within lipoprotein core
Q: By which process is cholesterol taken up by cells?
A: endocytosis
Q: Name 5 lipoprotein categories.
A: chylomicrons CM very low density lipoprotein VLDL Intermediate density lipoprotein IDL Low density lipoprotein LDL High density lipoprotein HDL
Q: What are chylomicrons?
A: fats are absorbed and packaged into them which travel in lymphatics from intestines to thoracic duct and subclavian vein where they enter blood stream
Q: What is lipoprotein lipase? Located? (3)
A: catalyses hydrolysis of triacylglycerols in chylomicrons to glycerol and fatty acids
Located on the capillary endothelial cells which line variety of tissues eg adipose, heart and skeletal muscle
Q: Which is good/bad: HDLs and LDLs?
A: LDL- bad cholesterol
HDL- good cholesterol
Q: Familial hypercholesterolaemia. Genetics? (2) What can occur in adolescence? What do patients lack? What gives rise to it?
A: monogenic dominant trait
Homozygotes = severely affected with very high serum cholesterol
severe atherosclerosis and coronary infarction
They lack functional LDLRs LDL-receptors on cell surface membrane of cells that take up LDLs
Given rise by mutations in LDLR gene
Q: What are LDL receptors responsible for? Result?
A: LDL receptors are responsible for receiving LDLs and sending them to the early endosome where they’re recycled back to the plasma membrane
The LDLs are transferred to lysosomes where it is degraded to give free cholesterol
Q: Recall pharmacological agents that may be used to control cholesterol metabolism. (2) (1-example, 2-function, result)
A: HMG-CoA reductase inhibitors (AKA stains)
-Lovastatin is a competitive inhibitor of HMG-CoA reductase
Resins/ sequestrants
Bind/sequester bile acid-cholesterol complexes preventing their reabsorption by the intestine
Lowers LDL levels and raises HDL
Q: What plays a key role in activating lipoprotein lipase?
A: apoprotein c-II on the chylomicron
Q: What occurs to the products of triacylglycerol hydrolysis? (2)
A: glycerol = returned to liver = used in gluconeogenesis
FA= beta oxidation
Q: What can isoprenoids do? Give 2 examples.
A: covalently attach to proteins to help anchor them in biological membranes
Farnesyl, geranylgeranyl groups
Q: What can isoprenoids do? Give 2 examples.
A: covalently attach to proteins to help anchor them in biological membranes
Farnesyl, geranylgeranyl groups
Q: Describe step 2 of cholesterol synthesis.
A: Mevalonate —phosphorylation at hydroxyl groups at position 3 and 5 —then decarboxylation —> 3-isopentenyl pyrophosphate
Q: What does prolonged elevation of LDL levels lead to? Function? Specific component?
A: Prolonged elevation of LDL levels leads to atherosclerosis
Function to take cholesterol Liver —> peripheral tissue
>40% of weight is made up of cholesterol esters
Q: What’s the function of HDLs? Use?
A: Function to take cholesterol from Peripheral tissue —> liver for use or disposal (reverse cholesterol transport)
Help lower total serum cholesterol
