Ch 32 pp 724-736

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Questions and Answers

What is the first and rate-limiting reaction in the synthesis of bile salts?

Oxidation reaction removing three carbons from the side chain

Addition of an α-hydroxyl group to carbon 7 (correct)

Reduction of the double bond in the B-ring

Hydroxylation at positions 3, 7, and 12

What percentage of bile acid molecules are present in the protonated form in the contents of the intestinal lumen?

75%

50% (correct)

25%

10%

Which series of bile salts is produced from compounds with α-hydroxyl groups at positions 3, 7, and 12?

Chenodeoxycholic acid series

Deoxycholic acid series

Cholic acid series (correct)

Chenocholic acid series

What is the pKa of the bile acids?

Approximately 6 Signup and view all the answers

What decreases the activity of 7α-hydroxylase, the enzyme catalyzing the first and rate-limiting reaction in bile salt synthesis?

Increase in bile salt concentration Signup and view all the answers

What is the remaining fragment attached to the ring structure after three carbons are removed from the side chain in bile salt synthesis?

Five-carbon fragment with a carboxyl group Signup and view all the answers

Which lipoprotein particle contains specific apolipoproteins on its surface that act as ligands for specific plasma membrane receptors on target tissues?

LDL Signup and view all the answers

Which enzyme can remove triacylglycerol from HDL3 particles to regenerate HDL2 particles?

Hepatic lipase Signup and view all the answers

What is the primary form of cholesterol esters in LDL?

Linoleate Signup and view all the answers

What process leads to the binding of the SREBP to the sterol-regulatory element of genes for the LDL receptor?

Feedback regulation Signup and view all the answers

What is the main mechanism of statin drugs in lowering blood LDL levels?

Upregulation of LDL receptors Signup and view all the answers

What happens when intracellular levels of cholesterol decrease?

Synthesis of the LDL receptor is stimulated Signup and view all the answers

What is the primary function of bile salts in the intestine?

Aid in lipid digestion Signup and view all the answers

Where are over 95% of bile salts resorbed and recycled in the body?

Ileum Signup and view all the answers

What is the primary function of lipoproteins in the bloodstream?

Transport cholesterol and cholesterol esters Signup and view all the answers

Which lipoprotein is assembled from dietary lipids within the epithelial cells of the small intestine?

Chylomicrons Signup and view all the answers

What is the main function of ApoCII within the lipoprotein shell?

Activates lipoprotein lipase (LPL) Signup and view all the answers

Which component of bile salts affects their solubility and ionization in the gut?

Conjugation with glycine or taurine Signup and view all the answers

What is the fate of VLDL remnants in the body?

They are taken up by the liver cells through receptor-mediated endocytosis Signup and view all the answers

What is the consequence of excess LDL particles in the body?

Nonspecific uptake by macrophages near the endothelial cells of arteries, potentially initiating atherosclerosis Signup and view all the answers

What is the treatment for familial lipoprotein lipase deficiency?

Low-fat diet and addition of medium-chain fatty acids Signup and view all the answers

What is the role of VLDL in lipoprotein metabolism?

Transporting triacylglycerols to muscle, adipose tissue, and mammary tissues Signup and view all the answers

What is the consequence of familial lipoprotein lipase deficiency?

Hyperchylomicronemia and various symptoms Signup and view all the answers

What happens to chylomicron remnants after being taken up by the liver?

Depleted of core triacylglycerols and retaining apoE and apoB-48 Signup and view all the answers

What is the major benefit of HDL?

Transporting cholesterol from cells to the liver Signup and view all the answers

Which protein is involved in facilitating the directional movement of cholesterol from the cell to the lipoprotein particle?

ABCA1 Signup and view all the answers

What is the role of LCAT in HDL metabolism?

Transferring fatty acids from lecithin to cholesterol Signup and view all the answers

What is the consequence of mutations in the ABCA1 protein?

Low levels of HDL and early-onset coronary artery disease Signup and view all the answers

How is mature HDL primarily cleared from the blood?

Uptake by the scavenger receptor SR-B1 Signup and view all the answers

What is the purpose of CETP inhibitors in HDL metabolism?

To increase atheroprotective HDL3 levels Signup and view all the answers

Study Notes

HDL Metabolism and Function

HDL takes on a more globular shape as the central hollow core fills with cholesterol esters, forming the mature HDL particle.
HDL's major benefit is its ability to remove cholesterol from cells and return it to the liver, known as reverse cholesterol transport.
Reverse cholesterol transport involves the directional movement of cholesterol from the cell to the lipoprotein particle, facilitated by the protein ABCA1.
LCAT, acquired by the HDL particle from the circulation, catalyzes the transfer of a fatty acid from lecithin to cholesterol, trapping the cholesterol within the HDL core.
Familial HDL deficiency and Tangier disease result from mutations in the ABCA1 protein, leading to low levels of HDL and early-onset coronary artery disease.
Treatment with ezetimibe, a drug that blocks cholesterol absorption, was added to complement atorvastatin to lower blood LDL cholesterol levels in a patient with intermittent chest pain.
Elevated levels of lipoprotein-associated cholesterol, particularly LDL, are associated with atherosclerotic plaque formation and cardiovascular events.
Mature HDL particles can bind to specific receptors on hepatocytes and are primarily cleared from the blood through uptake by the scavenger receptor SR-B1.
SR-B1 receptors transfer cholesterol and cholesterol esters into cells, dissociating the HDL particle when depleted and upregulating in cells that require cholesterol for biosynthesis.
HDL exchanges apolipoproteins and lipids with other lipoproteins in the blood, transferring apoE and apoCII to chylomicrons and VLDL and obtaining free cholesterol from cell membranes.
HDL either transports the free cholesterol and cholesterol esters directly to the liver or transfers them to circulating triacylglycerol-rich lipoproteins via CETP, exchanging triacylglycerols back to HDL.
CETP inhibitors are being evaluated to increase HDL2 levels, as high concentrations of triacylglycerol-rich lipoproteins generate elevated levels of less atheroprotective HDL3.

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Description

Test your knowledge of HDL metabolism and function with this quiz. Explore the role of HDL in reverse cholesterol transport, its interaction with proteins like ABCA1 and LCAT, and the impact of mutations and treatments on HDL levels. Gain insights into the relationship between HDL and atherosclerosis, as well as its role in lipid exchange and cholesterol transport.