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MCD Metabolism > 7 Cholesterol > Flashcards

7 Cholesterol Flashcards

1
Q

Q: What is cholesterol and what is its role? depending on? (2) changes?

A

A: steroid hormone

affects membrane stiffness depending on temperature and membrane type

changes interactions with the cytoskeleton

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2
Q

Q: What are the 4 parts of cholesterol synthesis?

A

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)

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3
Q

Q: Describe step 1 of cholesterol synthesis. (2)

A

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)

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4
Q

Q: Describe step 3 of cholesterol synthesis. (4)

A

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)

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5
Q

Q: Describe step 4 of cholesterol synthesis. (3)

A

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

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6
Q

Q: What is cholesterol the basis of?

A

A: steroid hormones

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7
Q

Q: What are the 5 classes of steroid hormones? And what is their precursor?

A

A: precursor is pregnenolone which is generated from cholesterol, E: desmolase

Cholesterol (C27)
          I
         \/
Prognenolone (C21)
          I
         \/
PROGESTAGENS (C21)
          I
         \/
GLUCOCORTICOIDS (C21)

+ MINERALOCORTICOIDS (C21)

+ ANDROGENS (C19)
I
\/
ESTROGENS (C18)

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8
Q

Q: What is bile? Summarise the synthesis of bile acids.

A

A: bile salts are major breakdown products of cholesterol

Cholesterol is converted by a series of reactions to primary bile salts GLYCOCHOLATE + TAUROCHOLATE

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9
Q

Q: Explain the mechanism of transport of cholesterol around the body.

A

A: forms lipoproteins to overcome (packaged within) transportation issue of lipids being insoluble in aqueous solutions

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10
Q

Q: What occurs when bile salts form mixed micelles?

A

A: hydrophobic tails in towards triacylglycerols TAGs

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11
Q

Q: What are lipid rafts? Role?

A

A: fluctuating assemblies of cholesterol and sphingolipids that organise processes eg. cell signalling

They localise key proteins such as the cell surface receptors

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12
Q

Q: What do lipoproteins consist of? (4)

A

A: Phospholipid monolayer - unesterified cholesterol and apoproteins

Core of cholesteryl esters and triacylglycerols

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13
Q

Q: What is the role of apoproteins? Different cells?

A

A: allow recognition of particle (lipoprotein) by tissues

The different types have varying apoproteins content which allows recognition by different cell types

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14
Q

Q: How are cholesterol esters synthesised? (2) ACAT? What’s their purpose?

A

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

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15
Q

Q: By which process is cholesterol taken up by cells?

A

A: endocytosis

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16
Q

Q: Name 5 lipoprotein categories.

A 
A: chylomicrons CM
very low density lipoprotein VLDL
Intermediate density lipoprotein IDL
Low density lipoprotein LDL
High density lipoprotein HDL
17
Q

Q: What are chylomicrons?

A

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

18
Q

Q: What is lipoprotein lipase? Located? (3)

A

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

19
Q

Q: Which is good/bad: HDLs and LDLs?

A

A: LDL- bad cholesterol

HDL- good cholesterol

20
Q

Q: Familial hypercholesterolaemia. Genetics? (2) What can occur in adolescence? What do patients lack? What gives rise to it?

A

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

21
Q

Q: What are LDL receptors responsible for? Result?

A

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

22
Q

Q: Recall pharmacological agents that may be used to control cholesterol metabolism. (2) (1-example, 2-function, result)

A

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

23
Q

Q: What plays a key role in activating lipoprotein lipase?

A

A: apoprotein c-II on the chylomicron

24
Q

Q: What occurs to the products of triacylglycerol hydrolysis? (2)

A

A: glycerol = returned to liver = used in gluconeogenesis

FA= beta oxidation

25
Q

Q: What can isoprenoids do? Give 2 examples.

A

A: covalently attach to proteins to help anchor them in biological membranes

Farnesyl, geranylgeranyl groups

26
Q

Q: What can isoprenoids do? Give 2 examples.

A

A: covalently attach to proteins to help anchor them in biological membranes

Farnesyl, geranylgeranyl groups

27
Q

Q: Describe step 2 of cholesterol synthesis.

A

A: Mevalonate —phosphorylation at hydroxyl groups at position 3 and 5 —then decarboxylation —> 3-isopentenyl pyrophosphate

28
Q

Q: What does prolonged elevation of LDL levels lead to? Function? Specific component?

A

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

29
Q

Q: What’s the function of HDLs? Use?

A

A: Function to take cholesterol from Peripheral tissue —> liver for use or disposal (reverse cholesterol transport)

Help lower total serum cholesterol

MCD Metabolism (11 decks)

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