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MEH > Lecture 4- Lipid Transort > Flashcards

Lecture 4- Lipid Transort Flashcards

1
Q

Why might GP’s find lipid profiles useful?

A

Can look at these in blood samples and see if patient is at potential risk of atherosclerosis due to high quantities of LDL’s etc

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2
Q

How are lipids transported?

A

2% bound to albumin the rest in lipoproteins

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3
Q

What structure is a lipoprotein?

A

Amphiphatic monolayer that contains triacylglycerol inside it

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4
Q

Which cholesterol is bad cholesterol?

A

There is no such thing as bad cholesterol just the lipoproteins that carry it. Reducing cholesterol reduces the bad lipoproteins

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5
Q

Why is cholesterol important?

A

Essential component of membranes

Precursor for steroid hormones like testosterone and cortisol

Precursor of bile acids

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6
Q

What is cholesterol transported around the body as?

A

Cholesterol ester

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7
Q

Integral vs peripheral apoproteins?

A

Integral= embedded

Peripheral= on surface

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8
Q

What do lipoproteins carry?

A

Triacylglycerol

Cholesterol

Fat soluble vitamins

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9
Q

What are the five classes of lipoproteins?

A

Chylomicrons

VLDL’s

LDLs

HDLs

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10
Q

What are the main fat carrying lipoproteins?

A

Chylomicrons which transport fats from GI tract through lymph and into subclavian vein to br borough to adipose tissue etc

VLDLs

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11
Q

What are the mainly cholesterol transporting lipoproteins?

A

IDLs

HDLs

LDL’s

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12
Q

What is the function of HDL’s

A

These lipoproteins are very good for you as they transport excess cholesterol from adipose tissue etc back to the liver for disposal. Also removes cholesterol deposited in walls of blood vessels

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13
Q

What is the problem with LDLs?

A

They have a very long half life which leaves them susceptible to oxidation by free radicals. They are then consumed by macrophages who now with a high fat content become foam cells. These foam cells deposit in arteries and result in the formation of a fatty streak. This fatty streak can cause atherosclerosis and lead to angina or rupture and subsequent clotting (thrombosis) which can result in stroke or myocardial infarction

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14
Q

Apoprotein function?

A

Structural: packing water insoluble lipid

Functional: ligand for cell surface receptors (endocytosis of LDLs)

Co-factor for enzymes

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15
Q

What does lipoprotein lipase do?

A

Hydrolysed triacylglycerol in lipoproteins to fatty acid and glycerol

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16
Q

How are chylomicrons metabolised?

A

Take up fat, cholesterol and fat soluble vitamins in small intestine. Travels through lymp and thoracic duct before joining circulation at left subclavian vein. Lipoprotein lipase on walls of capillaries at muscle and adipose tissue split triacylglycerol into glycerol and fatty acids to be used by tissues. Chylomicron remnants returned to liver and taken up through receptor mediated endocytosis by hepatocytes. Remaining contents degraded by lysosomes and what’s left used in metabolism

17
Q

VLDL metabolism?

A

Made in liver to transport synthesised fat to tissues. As fat is deposited after binding to lipoprotein lipase on endothelial walls VLDL becomes LDL and IDL

18
Q

LDL and IDL metabolism

A

When VLDL down to 30% of contents forms IDL and at 10% forms LDL which has a high cholesterol content= problematic when consumed by macrophages

19
Q

Why is LDL cleared poorly by the liver?

A

Lacks apoE which the liver recognises for receptor mediated endocytosis and so a lot of VDL remains in circulation

20
Q

How are lipoproteins related to Kwashiorkor?

A

Lack of apolipoproteins results in flat accumaulation and fatty liver

21
Q

How are LDL’s taken up by cells

A

Receptor mediated endocytosis

22
Q

What are the two ways that lipoprotein contents get into cells?

A

Receptor mediated endocytosis and lipoprotein lipase

23
Q

How are HDLs synthesised and why are they important?

A

Synthesised by liver and intestines in an empty form when TAGg levels are low. They can also bud off from chylomicrons and VLDL as they are digested by lipoprotein lipase. They accumulate cholesterol and phospholipids from cells lining the blood vessels

24
Q

What cells often take cholesterol from HDLs?

A

Steroidogenic cells

25
Q

What does LCAT or lecithin cholesterol acyltransferase do?

A

Converts cholesterol to cholesterol ester

26
Q

What is the function of each lipoprotein?

A

Chylomicrons= TAG from small intestine to tissues

VLDL= transfer of TAG synthesised in the liver to tissues

IDL and LDL= transport synthesised cholesterol from liver to tissues.

HDL= transport of excess cholesterol from cells to liver for disposal as bile salts and to cells requiring cholesterol as a precursor for synthesis

27
Q

What are the two main causes of hyperlipoproteinaemias?

A

Over production or under removal. There are 6 classes.

2A is associated with defective LDL receptor

Type 1 associated with chylomicrons is caused by defective lipoprotein lipase

28
Q

What are three clinical signs of khypercholesterolaemia?

A

Xanthelasma= yellow patches on eyelids

Tendon xanthoma= nodules on tendon

Corneal arcus= white circle around the eye

29
Q

How do you trade hyperlipoproteinaemias?

A

First approach is diet and lifestyle modification

Reduce cholesterol and saturated lipids in diet and increase fibre intake.

Increase exercise and stop smoking

Second approach only to be used if first one fails. Uses drugs eg HMG-CoA reductase inhibitor eg atorvastatin

Use bile salts sequesterants eg colestipol which bind bile salts and force liver to produce more

30
Q

Why are bile salt sequestering agents such as colestipol and fibre good to have in the diet?

A

Liver removes cholesterol as bile salts however these can be used to recycle cholesterol. If bile salts are sequestered and secreted liver must look for alternative pathways for cholesterol

31
Q

Cholesterol test levels?

A

Total cholesterol kinder 5mmol/L ideally

Non HDL cholesterol under 4mmol/L ideally

LDL less that 3mmol/L

HDL over 1 for men over 1.2 for women

TAG under 2mmol/L in fasted sample

Total cholesterol: HDL-C ratio of over 6 is high risk. The lower the better

32
Q

Why is lecithin cholesterol acyltransferase important?

A

Maintains the balance between ratio of surface to core lipids in the lipoprotein. An unbalance can lead to failure to transport TAG properly

33
Q

What is dyslipoproteinaemia?

A

A defect in the metabolism of plasma lipoproteins. Can easily lead to hyperlipoproteinaemias

MEH (17 decks)

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