1-Humans get cholesterol from the diet or they synthesize it from Acetyl CoA. An
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Question
1-Humans get cholesterol from the diet or they synthesize it from Acetyl CoA. An adult on a low cholesterol diet synthesizes around 600 mg cholesterol per day. This amount drops dramatically if the person transitions to a redmeat diet. Give a mechanistic explanation for this observation!
2- The amount of HMG-CoA reductase can increase substantially in patients treated with statins. What might be the reason for this side effect?
3- Why do you think some doctors suggest that patients treated with statins also take a coenzyme Q supplement?
4-Why is a drug that prevent reuptake of bile acids often taken together with statins?
5- How many moles of ATP are needed to synthesize one mole of lanosterol (precursor to cholesterol)?
6-Which diet do you think make a person more prone to generate ketone bodies; a “no-carb diet” or a “no-carb diet” supplemented with glucogenic amino acids such as aspartate and valine? Justify very briefly.
Explanation / Answer
(2)
The lipid lowering statins have a structure similar to mevalonate, which is an intermediate in cholesterol synthesis.
Due to this similarity, in the pathway of cholesterol synthesis, the HMG-CoA does not get reduced further to mevalonate and the pathway kind of gets 'blocked' at this step. This in turn increases the HMG-CoA reductase levels back again.
(3)
Generally, the use of statins comes with the side effects like muscle pain, nausea and diarrhea,liver and kidney damage, and increased blood sugar levels.
A Coenzyme , generally CoQ10, is supplemeted to counter these side effects to some extent.
(4)
Drugs that prevent re-uptake of bile acida are termed bile acid resins or sequestrants. They also act as lipid lowering agents like statins.
Prevention of bile acid uptake causes a contraction of the bile acid pool, leading to increased bile acid synthesis. This in turn competes with cholesterol synthesis in the liver, thus effectively lowering the cholesterol levels as well.
(5)
36 moles of ATP are required for the production of 1 mole lanosterol. 18 are used in conversion of 18 moles of citrate to acetyl CoA in the first step.
Next 18 are consumed by 6 moles of Mevalonate ( 3 ATP each ) for conversion to isopentenyl pyrophosphate.
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