Biosynthesis of Cholesterol

These flashcards cover key concepts regarding the biosynthesis and metabolism of cholesterol, including its functions, synthesis stages, disorders related to metabolism, and pharmaceutical interventions.

What are two key functions of cholesterol in the body?

Component of cell membranes and precursor of bile acids, steroid hormones, and Vitamin D.

What is the main site of cholesterol synthesis?

Liver.

What percentage of cholesterol is synthesized in the body?

Approximately 70%.

What dietary sources contribute to cholesterol intake?

Only animal sources like eggs, meat, and milk.

What range of cholesterol is typically consumed in a Western diet daily?

500-2000 mg.

Which enzyme plays a regulatory role in the first stage of cholesterol synthesis?

HMG-CoA Reductase.

What are the initial substrates used to synthesize cholesterol?

Acetyl-CoA.

What are the three moles of activators required in the energetic cost of cholesterol production?

18 moles of acetyl CoA, 18 moles of ATP, and 16 moles of NADPH.

Describe the second stage of cholesterol synthesis.

Mevalonate forms Active Isoprenoid Units, specifically farnesyl pyrophosphate.

What final compound is formed from mevalonate during stage 2?

Farnesyl pyrophosphate.

What enzyme is used in the condensation of two molecules of farnesyl pyrophosphate?

Squalene Synthase.

What is the purpose of bile acids?

To assist in the digestion of dietary fat as emulsifiers.

What percentage of bile acids is reabsorbed in the enterohepatic circulation?

Up to 98%.

What is the proposed mechanism by which Vitamin C deficiency leads to cholesterol accumulation?

Decreased activity of 7 alpha hydroxylase leading to decreased bile acid production.

Which drug class inhibits HMG-CoA Reductase?

Statin drugs.

List two examples of statin drugs.

Lipitor and Zocor.

What is a common side effect of statin drugs regarding nutritional supplementation?

Inhibition of the synthesis of CoQ10, requiring supplementation.

How do lifestyle factors like smoking and lack of exercise affect cholesterol levels?

They elevate blood cholesterol levels.

How is intracellular cholesterol concentration influenced?

By the inhibition of cholesterol biosynthesis and downregulation of LDL receptors.

What is the end product of cholesterol metabolism?

It cannot be digested and is primarily eliminated in feces.

What role does bran, specifically oat bran, play in cholesterol management?

It binds cholesterol and bile acids, helping to excrete them in feces.

Which disease can result from cholesterol metabolism disorders?

Cardiovascular disease.

What are gall stones, and how are they diagnosed?

They are not visible on X-ray and are diagnosed using a cholecystogram (ultrasound).

What is the function of bile acids after being synthesized in the liver?

They are secreted to aid in fat digestion.

What physiological conditions can increase cholesterol levels in the body?

De novo biosynthesis and dietary intake.

Which enzyme's activity is increased by insulin and T3 thyroid hormones?

HMG-CoA Reductase.

What are secondary bile acids, and where are they formed?

Deoxycholic acid and lithocholic acid; they are formed in the intestine.

Where does the conversion of squalene to lanosterol take place?

In the cell membrane or endoplasmic reticulum.

Describe the process of cholesterol metabolism and how cholesterol is eliminated from the body.

Cholesterol is removed from the body by being transferred into the gut for fecal excretion.

What non-invasive method can be used to assess gall stones?

Cholecystogram (ultrasound).

What is the primary product of cholesterol synthesis that acts as a precursor to steroid hormones?

Pregnenolone.

What are the consequences of elevated serum free fatty acids?

They can lead to increased blood cholesterol levels.

Describe the pathway from cholesterol to testosterone.

Cholesterol is converted to pregnanolone, then to androstenedione, and finally to testosterone.

Identify two factors that decrease intracellular free cholesterol concentration.

Inhibition of cholesterol biosynthesis and downregulation of LDL receptors.

What substances are necessary to form bile acids from cholesterol?

NADPH, O2, and cytochrome P450.