L14 Cholesterol and Lipoprotein Metabolism Flashcards

1
Q

What is the composition of a triglyceride?

A

Glycerol backbone and three fatty acids

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2
Q

What is the composition of a phospholipid?

A

Two fatty acids attached to glycerol and phosphate with a variable head group

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3
Q

What are some roles of cholesterol? (good and not so good) (3)

A
  • Structural component of cell membrane for cell integrity and fluidity
  • Precursor of steroid hormones, vitamin D and bile acids
  • Accumulation in arteries leading to CHD and stroke
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4
Q

Where is cholesterol mainly synthesised?

A

Liver and intestine, however can be synthesised in all cells

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5
Q

What is cholesterol synthesis controlled by? (3)

A
  • Dietary intake
  • Cholesterol levels
  • Hormones
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6
Q

What condition do ‘statins’ treat?

A

Hypercholesterolaemia

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7
Q

How are cholesterol levels normally balanced?

A

Balance between intake, synthesis, use, reabsorption and excretion

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8
Q

What is HMG-CoA reductase?

A

A rate limiting enzyme to control cholesterol synthesis

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9
Q

What is the structure of a lipoprotein?

A

Polar surface with phospholipids, cholesterol and proteins
Non-polar lipid core with TGs and cholesteryl esters

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10
Q

What is the main component of chylomicrons? Is it the highest or lowest density?

A

Triglycerides
Lowest density due to its high fat and low protein content

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11
Q

What is the main component of VLDL?

A

Triglycerides

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12
Q

What is the main component of LDL?

A

Cholesterol

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13
Q

What is the main component of HDL?

A

Protein

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14
Q

Where are chylomicrons produced?

A

Inside enterocytes

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15
Q

Where are VLDLs produced?

A

In the liver from chylomicron remnants and lipids

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16
Q

How are LDLs produced?

A

From VLDL (via IDL) after lipoprotein lipase removes triglycerides

17
Q

Where are HDLs produced?

A

Initiated in the liver but mature in circulation

18
Q

What apo-lipoporotein is associated with HDL?

19
Q

What apo-lipoporotein is associated with LDL and VLDL?

20
Q

What apo-lipoporotein is associated with chylomicrons and chylomicron remnants?

21
Q

What is the main function of lipoproteins? (1)
What are its three pathways? (3)

A
  • Used for transporting lipids
  • Exogenous pathway - digestive system to liver
  • Endogenous pathway - liver to other tissues
  • Reverse transport - from tissues back to the liver
22
Q

What are functions of apolipoproteins? (2)

A
  • Helping stabilise lipoproteins
  • Interact with receptors on cell surfaces
23
Q

How does the exogenous lipid transport pathway work? (4 steps)

A
  • Dietary lipids are packaged into chylomicrons inside enterocytes
  • Chylomicrons are absorbed into the lymphatic system via lacteals
  • Then enter the bloodstream via thoracic and right lymphatic ducts
  • Remodelling of chylomicrons
24
Q

How do chylomicrons work? (4 steps)

A
  • Chylomicrons interact with capillaries of muscle and adipose tissue
  • Lipoprotein lipase hydrolyses TGs
  • FAs and glycerol enter the cell for storage or fuel
  • Converted into chylomicron remnants that travel back to the liver
25
Q

How does the VLDL lipid transport pathway work? (3 steps)

A
  • Liver produces VLDLs which carry TGs and cholesteryl esters to tissues
  • Lipoprotein lipase removes TGs from VLDL to cells
  • Removal of TGs result in VLDL remnants which are mostly returned to the liver
26
Q

How is LDL formed? (3 steps)

A
  • Remaining VLDL remnants in circulation become IDLs
  • Some IDLs are reabsorbed by the liver via LDL receptor
  • Remaining IDLs are hydrolysed by hepatic lipase which forms LDLs
27
Q

What lipoprotein is the main lipoprotein that transports cholesterol to cells in the body?

28
Q

How is LDL taken up by cells? (3 steps)

A
  • LDL’s apoB-100 binds to LDL receptor (LDLR) on the cell surface
  • LDLR-mediated endocytosis occurs; cell membrane encloses LDL into a vesicle which enters the cell
  • LDL is hydrolysed and cholesterol is released
29
Q

What is the chain of events from an oversupply of cholesterol? (6)

A
  • Increased intracellular cholesterol
  • Inhibited cholesterol synthesis
  • Inhibited LDLR synthesis
  • Down-regulation of LDLR synthesis
  • Decreased LDL uptake
  • Hypercholesterolaemia
30
Q

What happens when there is excess LDL? (2)

A
  • LDL accumulates in the arterial walls
  • May become oxidised leading to atheroma formation
31
Q

How do HDL particles fill with cholesterol? (1)

A

By ApoAI binding to ABCAI

32
Q

Describe HDL maturation (3 steps)

A
  • HDL binding to ABCAI causes efflux of free cholesterol and phospholipids
  • Free cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT) and stored as cholesterol esters
  • Cholesterol esters move to hydrophobic core of particle and produces a mature HDL
33
Q

Describe HDL reverse transport - direct pathway (2)

A
  • HDL particles circulate and remove cholesterol from cells, and pick up phospholipids via phospholipid transport protein (PLTP)
  • HDL then delivers cholesterol to the liver or steroidogenic organs such as adrenals, testes and ovaries
34
Q

a) What does HDL use in its indirect transport pathway? (1)
b) What does it promote the transfer of? (2)
c) Why is this pathway beneficial? (1)

A

a) Cholesteryl ester transfer protein (CETP)
b) Promotes the transfer of:
- TG from VLDL and LDL to HDL
- Cholesterol esters from HDL to VLDL and LDL
c) Enables HDLs to stay in circulation to remove cholesterol