Ch 32 pp 716-724

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Questions and Answers

What is the precursor for cholesterol synthesis?

Hydroxymethylglutaryl CoA (HMG-CoA)

Acetoacetyl CoA

Mevalonate

Acetyl coenzyme A (acetyl CoA) (correct)

Where does cholesterol synthesis primarily occur in the body?

Lungs

Liver, intestine, adrenal cortex, and gonads (correct)

Spleen

Kidneys

In which form can cholesterol appear in blood lipoproteins?

Free, unesterified form in the outer shell and as cholesterol esters in the core (correct)

As a part of triglycerides

Only as cholesterol esters in the core

Only in its free, unesterified form in the outer shell

What is the active form of vitamin D produced in the skin?

Cholecalciferol Signup and view all the answers

What is the relationship between cholesterol concentrations in blood and the development of atherosclerotic vascular disease?

There is a direct relationship Signup and view all the answers

What is the main function of cholesterol in the body?

Stabilizing component of cell membranes and synthetic precursor of bile salts and steroid hormones Signup and view all the answers

Which enzyme phosphorylates HMG-CoA reductase?

Adenosine monophosphate (AMP)-activated protein kinase Signup and view all the answers

What effect does glucocorticoids have on the activity of HMG-CoA reductase?

Decreases its activity Signup and view all the answers

Where does most of the biosynthesis of cholesterol occur?

Liver cells Signup and view all the answers

What is the primary transporter of cholesterol esters from the liver to the tissues?

VLDL Signup and view all the answers

What is the fate of residual cholesterol esters not used by tissues?

Stored in the liver for later use Signup and view all the answers

What is the primary source of cholesterol for the synthesis of bile acids?

Hepatic cholesterol pool Signup and view all the answers

Which lipoprotein particles package cholesterol in the intestine?

Chylomicrons Signup and view all the answers

What is the major rate-limiting step of cholesterol synthesis?

HMG-CoA reductase catalysis Signup and view all the answers

Which lipoprotein particles endocytose LDL?

Nonhepatic tissues Signup and view all the answers

What is the primary function of bile salts produced in the liver?

Aid in digestion by emulsifying dietary triacylglycerols Signup and view all the answers

What percentage of bile salts that enter the lumen of the small intestine are eventually excreted in feces?

Less than 5% Signup and view all the answers

Which test isolates LDL cholesterol and is not affected by mildly to moderately elevated serum triacylglycerol levels?

LDL direct Signup and view all the answers

Which protein is involved in reverse cholesterol transport and HDL biogenesis?

ABCA1 Signup and view all the answers

What is the main route for cholesterol elimination from the body?

Feces Signup and view all the answers

Which genetic condition results from a defect in ABCG5 or ABCG8 function?

Sitosterolemia Signup and view all the answers

How does Ezetimibe lower serum cholesterol levels?

By blocking cholesterol absorption through NPC1L1 protein Signup and view all the answers

Which pathway provides NADPH required for cholesterol synthesis?

Pentose phosphate pathway Signup and view all the answers

What is the committed, rate-limiting step in cholesterol formation?

Catalysis of mevalonate to cholesterol by HMG-CoA reductase Signup and view all the answers

What is the role of squalene monooxygenase in cholesterol biosynthesis?

It converts squalene into lanosterol, a precursor of cholesterol Signup and view all the answers

What is the function of HMG-CoA reductase in cholesterol biosynthesis?

It is the rate-limiting step of cholesterol biosynthesis Signup and view all the answers

How is the activity of HMG-CoA reductase controlled?

Through transcriptional regulation, proteolytic degradation, and covalent modification Signup and view all the answers

What is the role of geranyl pyrophosphate and farnesyl pyrophosphate in cholesterol biosynthesis?

They are key components in cholesterol biosynthesis Signup and view all the answers

What activates the carbon 5 and the hydroxyl group on carbon 3 for further reactions in cholesterol biosynthesis?

Phosphate transfers Signup and view all the answers

What is the first product of the removal of the phosphate group from the C3 hydroxyl group of mevalonate in cholesterol biosynthesis?

Δ3-isopentenyl pyrophosphate Signup and view all the answers

Study Notes

Cholesterol Biosynthesis and HMG-CoA Reductase Regulation

Phosphate transfers activate carbon 5 and the hydroxyl group on carbon 3 for further reactions in cholesterol biosynthesis.
Removal of the phosphate group from the C3 hydroxyl group of mevalonate produces Δ3-isopentenyl pyrophosphate, the first of two activated isoprenes for cholesterol synthesis.
Isoprenes are used for cholesterol biosynthesis, coenzyme Q synthesis, and dolichol synthesis.
Stage 3 of cholesterol biosynthesis involves the condensation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate to form geranyl pyrophosphate and farnesyl pyrophosphate.
Geranyl pyrophosphate and farnesyl pyrophosphate are key components in cholesterol biosynthesis and can form covalent bonds with proteins involved in signal transduction.
Squalene, a compound with 30 carbons, is formed from the fusion of two molecules of farnesyl pyrophosphate.
Squalene monooxygenase converts squalene into lanosterol, a sterol with the four-ring structure characteristic of the steroid nucleus, which ultimately forms cholesterol.
HMG-CoA reductase is the rate-limiting step of cholesterol biosynthesis and is the target of cholesterol-lowering drugs called statins.
Transcriptional regulation of HMG-CoA reductase is controlled by sterol-regulatory element-binding proteins (SREBPs) that directly activate the expression of genes dedicated to cholesterol synthesis.
Rising levels of cholesterol and bile salts may change the oligomerization state of HMG-CoA reductase, rendering the enzyme more susceptible to ubiquitination and proteolysis, decreasing its activity.
HMG-CoA reductase is also regulated by phosphorylation and dephosphorylation, with glucagon inactivating the enzyme and hyperinsulinemia increasing its activity.
The regulation of HMG-CoA reductase activity is controlled through transcriptional regulation, proteolytic degradation, and covalent modification.

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Test your knowledge of cholesterol biosynthesis and the regulation of HMG-CoA reductase with this quiz. Explore the key stages and components involved in cholesterol synthesis, as well as the mechanisms that control the activity of HMG-CoA reductase, the rate-limiting enzyme in this process.