Role of the liver is cholesterol metabolism?

Explain the role of the liver and gastro-intestinal tract in cholesterol metabolism.

This is a sample question from a past paper, and I understand how cholesterol is synthesised from acetyl CoA from food in the gastro intestinal tract, and that it is carried to the liver via the lymph system, where it is then used to synthesis bile and lipo-proteins, but thats where I get stuck as this question is worth 8 marks I think I have missed something. Can anyone help?

You've maybe got a little bit mixed up with where stuff happens, but you've essentially got the right processes in place. You have dietary cholesterol which with the aid of bile salts, acids and such is able to enter the mucosal cells of the gastro-intestinal tract and converted to chylomicrons by adding triglycerides and phospholipids. These pass into the blood stream and travel to the liver where they are processed to cholesterol and can be formed into the lipoproteins we have in our bodies. In addition to this, nutrients from our diet also pass to the liver or are obtained from elsewhere in the body and are converted to acetyl coA in the liver, which through a series of reactions can be converted into cholesterol, which again can be processed into the lipoproteins of the body. The liver provides tryglycerides and proteins in the synthesis of the lipoproteins.

The blood of course returns cholesterol already in the bloodstream back to the liver, but also it can be deposited straight back into the gastro-intestinal tract from the bloodstream. This again can be taken back up by the gastro-intestinal tract as dietary cholesterol and processed again by the gastro-intestinal tract and liver as mentioned before. The biliary system works mainly by means of the bile acids aiding in the digestion and subsequent uptake of dietary cholesterol components by the gastro-intestinal tract. The liver itself can pass cholesterol straight into the bile and again this goes back into the gastro-intestinal tract only to form part of the dietary cholesterol and return back into the system as mentioned before. The more important bile acids aside from their aiding digestion and absorption of dietary cholesterol also have a feedback mechanism, these bile acids can be re-absorbed by the gastro-intestinal tract and returned to the liver where their concentration obviously will increase. Now concentration of bile acids within the liver act as an inhibitor to the synthesis of cholesterol from mevalonic acid (one of the stages from acetyl coA to cholesterol pathway), so if a lot of bile acids are returning to the liver or if the excretion of bile from the liver is slowed for whatever reason, then the production of cholesterol from acetyl coA will ultimately be slowed.

Now the bile acids are of course an end product of metabolism of cholesterol and therefore considered waste in a sense and the ultimate fate of these is to pass into the gastro-intestinal tract and not be reabsorbed that particular time whereby the action of bacteria form them into cholesterol, coprostanol and various other steroids which pass out of the body in the faeces. That's about all I can think of involving the liver and the gastro-intestinal tract. Of course the whole system is more complex when including body tissues, sex hormones, blood and their various feedback systems as well but you weren't asked about that so it's unnecessary to mention.

Hope this helps