Question

1-What is the mechanism of action of a statin drug such as lovastatin and cholestyramine in regulating blood cholesterol concentration of humans? 2-Why would you expect a high intake of ethanol leads to greater output of lactate from liver into the blood? 3- Show how the hormonal form of vitamin D3 affects calcium absorption by your small intestine. 4-Some humans experience serious side effects in muscle function because of consumption of Lipitor®. Postulate why you think this may happen.

Answer 1

1. Statins imhiinh HMG- CoA reductase. It is a rate limiting enzyme of mevalonate pathway which is involved in cholesterol synthesis. Statins are similar in structure with HMG - CoA reductase, hence competes with it for the substrate binding. These ensures the limited formation of mevalonate which in turn controls cholesterol formation. Statins blocks the cholesterol formation in the liver. Hence the blood cholesterol levels drop. Reduced levels of cholesterol in the liver are compensated by increased LDL receptors , which will bind to LDL and VLDL lipids to reprocess cholesterol, hence reducing bad cholesterol.

2. Ethanol metabolism is associated with increased NADH/NAD⁺ ratio leading to conversion of pyruvate to lactate. Gluconeogenesis is also stalled leading to hyperlactatemia.

3.D3 i.e. chocalciferol is converted to active form of vitamin D3 by kidneys called as calciteiol.This circulated in blood as hormone which regulates calcium band phosphate balance in the body. It mediates the biological effects by binding to vitamin D receptors which are transcription factors for expression of genes involved in calcium absorption from small intestine. These receptors are present in bones, kidneys, parathyroid all of which are involved in calcium homeostasis. Activation of vi. D receptors by calcitriol is responsible for maintaining calcium balance in blood.

4. Lipitor is administered as a calcium salt. The enzymatic reaction with the substrate may create calcium imbalance in such a way that it could lead to muscle fatigue. Rhabdomyolysis is a sever side effect of Lipitor although rare. Weak muscles may undergo rupture releasing it's contents in the blood, which may cause kidney failure and is untreatable.