TBR: LDL Question

[justadream]

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TBR Bio I page 264 #62 says that

"An LDL particle is a low density lipoprotein which transports cholesterol from the liver to the body cells via the blood. The cells take up these particles through receptor mediated endocytosis. However, high levels of cholesterol will inhibit LDL receptor synthesis, and the particles will remain in the circulatory system. The build up of cholesterol in the blood is thought to be a prime cause of atherosclerosis..."

Can someone why high levels of cholesterol inhibits LDL receptor synthesis?

Why doesn't the body just take up the excess cholesterol (thus reducing atherosclerosis chances)?

 

[kraskadva]

It's a feedback loop.

Normal:
LDL gets snagged by receptor, endocytosed with receptor
Receptor degraded & new one made to replace it on the cell surface. Cholesterol used for cell functions or stored.

BUT, once the cell has all the cholesterol it needs, a checkpoint is set off and the cell will stop replacing the receptors on the cell surface by inhibiting the txn of that gene, so that no more cholesterol is brought in.

 

[Czarcasm]

Just to add onto what kraskadva said -- this scenario is very similar to what happens with water-soluble hormones in blood. Up-regulation of hormone receptors occurs when hormone levels are low, but down-regulation of receptors occurs when hormone levels are high. In this way, cells can also regulate the input they receive to ensure it's not excessive or minimal. This is one of the primary explanations for the cause of diabetes type II. Beta cells of obese individuals produce large amounts of insulin which circulates the blood and cells respond by down-regulating the receptors on their surface, causing insulin resistance. LDL receptors function in a similar fashion, but the key difference here is that the receptors themselves are endocytosed (hormone receptors are not), degraded, and the materials recycled. Only when cholesterol levels are sufficiently low, are receptors regenerated and sent to the plasma membrane.