2. Cholesterol is an important component of cell membranes, yet high levels of circulating cholesterol are associated with an increased risk of coronary heart disease. a. Summarise the mechanisms that control cholesterol biosynthesis. b. Why do bile sequesterants help to reduce levels of circulating cholesterol?

a. The mechanisms that control cholesterol biosynthesis are complex and involve several steps. The process begins in the cytoplasm, where the molecule acetyl-CoA is converted into 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This is then reduced to mevalonate by the enzyme HMG-CoA reductase, which is the rate-limiting step in cholesterol synthesis. Mevalonate is then converted into isopentenyl pyrophosphate, which is used to form squalene. Squalene is then converted into lanosterol, which is finally converted into cholesterol. The production of cholesterol is tightly regulated by the body. When cholesterol levels are high, the body reduces the production of HMG-CoA reductase, thereby slowing down cholesterol synthesis. Additionally, excess cholesterol can be converted into bile acids in the liver and excreted in the feces.

b. Bile sequestrants, also known as bile acid binders, help to reduce levels of circulating cholesterol by binding to bile acids in the intestine. Bile acids are made from cholesterol in the liver and are used to digest dietary fats. When bile sequestrants bind to these acids, they form a complex that cannot be absorbed by the intestine. This forces the liver to use more cholesterol to produce new bile acids, thereby reducing the amount of cholesterol in the bloodstream. Additionally, the unabsorbed complex of bile acids and sequestrants is excreted in the feces, further reducing cholesterol levels.