9 lipoproteins + Cholesterol

What is cholesterol?

A sterol lipid essential for membranes, hormone synthesis, and bile acid production.

What is the role of cholesterol in cell membranes?

Regulates membrane fluidity and stability.

What molecules are synthesised from cholesterol?

Steroid hormones, vitamin D, and bile acids.

Examples of steroid hormones derived from cholesterol?

Progesterone, testosterone, oestradiol, cortisol.

Why must cholesterol levels be regulated?

Excess cholesterol causes pathological deposition, especially in arteries.

What determines plasma cholesterol levels?

Diet, endogenous synthesis, metabolism, excretion, and tissue use.

Can all cells synthesise cholesterol?

Yes, but liver and small intestine are major sites.

What is cholesterol homeostasis?

Balance between synthesis, uptake, use, and excretion.

What is the precursor for cholesterol synthesis?

Acetyl CoA.

How many steps are in cholesterol synthesis?

Approximately 26.

What is the rate-limiting step in cholesterol synthesis?

HMG-CoA reduction to mevalonate.

What enzyme catalyses the rate-limiting step?

HMG-CoA reductase.

Reaction catalysed by HMG-CoA reductase?

HMG-CoA → mevalonate.

What cofactor does HMG-CoA reductase require?

NADPH.

Why is HMG-CoA reductase important?

Main control point in cholesterol synthesis.

How does cholesterol regulate HMG-CoA reductase transcriptionally?

Inhibits mRNA synthesis.

How does cholesterol regulate HMG-CoA reductase translationally?

Reduces protein production.

How does cholesterol regulate HMG-CoA reductase post-translationally?

Promotes enzyme degradation.

How does AMPK affect HMG-CoA reductase?

Phosphorylation inhibits it.

Why does AMPK inhibit cholesterol synthesis?

Low energy state conserves ATP.

What drugs inhibit HMG-CoA reductase?

Statins.

How do statins lower cholesterol?

Reduce endogenous cholesterol synthesis.

Why are cholesterol and TAG transport difficult in plasma?

They are hydrophobic and poorly soluble.

How are cholesterol and TAG transported in blood?

In lipoproteins.

What is a lipoprotein?

A lipid-protein transport particle.

Structure of a lipoprotein?

Hydrophobic core + phospholipid/cholesterol shell + apolipoproteins.

What is in the lipoprotein core?

Triacylglycerol and cholesteryl esters.

What is in the lipoprotein shell?

Phospholipids, cholesterol, apolipoproteins.

What are apolipoproteins?

Proteins involved in lipoprotein structure and receptor recognition.

Major lipoprotein classes?

Chylomicrons, VLDL, IDL, LDL, HDL.

What do chylomicrons mainly transport?

Dietary triacylglycerol.

What does VLDL mainly transport?

Endogenous triacylglycerol.

What does IDL mainly transport?

Cholesteryl esters.

What does LDL mainly transport?

Cholesteryl esters.

What does HDL mainly transport?

Cholesterol/phospholipids for reverse transport.

How are lipoproteins named?

By density.

Why does HDL have high density?

High protein content.

Why do chylomicrons have low density?

Very high lipid content.

What is LDL?

The major cholesterol delivery particle.

What is the main apolipoprotein on LDL?

ApoB-100.

Function of ApoB-100?

Binds LDL receptors.

What is the role of LDL?

Deliver cholesterol to peripheral tissues.

What is the LDL receptor?

A cell surface receptor mediating LDL uptake.

How does LDL enter cells?

Receptor-mediated endocytosis.

Who discovered LDL receptor-mediated uptake?

Goldstein and Brown.

What happens after LDL binds its receptor?

Endocytosis into coated vesicles.

What happens to LDL after endocytosis?

Delivered to lysosomes, cholesterol released.

What happens to intracellular cholesterol after LDL uptake?

Used for membranes/hormones or stored.

How does LDL uptake affect cholesterol synthesis?

Reduces HMG-CoA reductase activity.

How does LDL uptake affect LDL receptor expression?

Reduces receptor synthesis.

Why is LDL called “bad cholesterol”?

High levels increase atherosclerosis risk.

What enzyme hydrolyses lipoprotein TAG?

Lipoprotein lipase.

Where is lipoprotein lipase located?

Capillary endothelial surfaces.

Major tissues with lipoprotein lipase?

Skeletal muscle, adipose tissue, heart.

Reaction catalysed by lipoprotein lipase?

TAG → fatty acids + monoacylglycerol.

What happens to fatty acids released by lipoprotein lipase?

Oxidised for energy or re-stored as TAG.

What happens to chylomicrons after TAG removal?

Become remnants.

What happens to VLDL after TAG removal?

Become IDL then LDL.

What is HDL’s major protective role?

Reverse cholesterol transport.

What is reverse cholesterol transport?

Removal of cholesterol from tissues/arteries back to liver.

Why is HDL considered “good cholesterol”?

Removes excess cholesterol.

What is familial hypercholesterolaemia (FH)?

Inherited LDL receptor deficiency.

Effect of FH on plasma LDL?

Markedly increased LDL.

Why does FH cause early heart disease?

Reduced LDL clearance causes cholesterol deposition.

What happens if LDL receptors are defective?

High circulating LDL.

Why is high LDL dangerous?

Promotes cholesterol accumulation in arteries.

What is atherosclerosis?

Cholesterol-rich plaque formation in arteries.

Main lipid in atherosclerotic plaques?

Cholesteryl esters.

How do foam cells form?

Macrophages take up modified LDL.

What are foam cells?

Cholesterol-loaded macrophages.

Why are foam cells dangerous?

Promote plaque growth and inflammation.

What can happen if an atherosclerotic plaque ruptures?

Thrombosis causing heart attack/stroke.

Major risk factors for atherosclerosis?

High LDL, saturated fat diet, reduced LDL receptors, FH.

How does saturated fat increase cardiovascular risk?

Raises LDL cholesterol.

How is cholesterol excreted?

Converted to bile acids.

What is the rate-limiting enzyme in bile acid synthesis?

Cholesterol 7α-hydroxylase.

Why are bile acids important?

Emulsify dietary lipids.

Where are bile acids released?

Into bile then small intestine.

What percentage of bile acids are reabsorbed?

Approximately 95%.

What is enterohepatic circulation?

Recycling of bile acids between liver and intestine.

Why is only a small fraction of cholesterol eliminated?

Most bile acids are reabsorbed.

How does HDL protect against atherosclerosis?

Removes cholesterol from lesions.

What is the key overall balance in cholesterol metabolism?

Synthesis + intake vs excretion + tissue uptake.