Cholesterol Overview

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Questions and Answers

What percentage of cholesterol in egg yolks is esterified?

70%

20%

50%

10% (correct)

What is the primary enzyme responsible for hydrolyzing cholesterol esters in the diet?

Acyl-CoA:cholesterol acyltransferase 2

Pancreatic lipase

Niemann-Pick C1 like 1

Cholesterol esterase (correct)

Which protein mediates the uptake of cholesterol into enterocytes?

ACAT2

Cholesterol esterase

NPC1L1 (correct)

Phytosterol transporter

What effect do phytosterols have on cholesterol absorption?

Displace cholesterol from micelles Signup and view all the answers

Which condition must be met for cholesterol to be incorporated into micelles?

Cholesterol must be hydrolyzed Signup and view all the answers

What is the daily dietary intake of cholesterol typically seen?

300 mg/day Signup and view all the answers

What is the fate of cholesterol that is not absorbed in the intestine?

It is excreted in feces Signup and view all the answers

How does efficient cholesterol absorption affect cholesterol homeostasis in the body?

It increases cholesterol retention in the body Signup and view all the answers

What is the primary function of low-density lipoprotein (LDL) concerning cholesterol?

It carries cholesterol to various tissues. Signup and view all the answers

How does high-density lipoprotein (HDL) contribute to cholesterol homeostasis?

By transporting free cholesterol from tissues to the liver. Signup and view all the answers

What is the primary component of cell membranes that interacts with cholesterol?

Phospholipids Signup and view all the answers

Which mechanism is utilized by cells to regulate excess cholesterol levels in membranes?

Esterification of excess cholesterol Signup and view all the answers

Which factor influences the fluidity and integrity of animal cell membranes?

The presence and concentration of cholesterol Signup and view all the answers

What is the role of SREBPs in cholesterol metabolism?

To regulate the synthesis of cholesterol and fatty acids. Signup and view all the answers

How does phytosterol intake affect cholesterol levels in the body?

It reduces cholesterol absorption in the intestines. Signup and view all the answers

Which strategy can be employed to manage hypercholesterolemia?

Using medications that inhibit cholesterol absorption. Signup and view all the answers

What is the primary role of the proteins ABCG5 and ABCG8 in cholesterol metabolism?

To redirect phytosterols and some cholesterol back into the intestinal lumen Signup and view all the answers

How does ezetimibe affect cholesterol absorption?

It inhibits NPC1L1, leading to reduced cholesterol absorption Signup and view all the answers

Which statement accurately describes the condition known as sitosterolemia?

It results from mutations in either ABCG5 or ABCG8, leading to hyperabsorption of cholesterol and phytosterols. Signup and view all the answers

What was the main active ingredient in the historical treatment for elevated blood cholesterol marketed as Cytellin?

Phytosterols Signup and view all the answers

In patients with familial hypercholesterolemia, what is the effect of adding ezetimibe to ongoing statin treatment?

It results in an additional reduction in LDL cholesterol of around 25%. Signup and view all the answers

What is the typical overall efficiency of cholesterol absorption in the human body?

50–60% Signup and view all the answers

What type of fatty deposits are indicative of high LDL cholesterol levels in patients with familial hypercholesterolemia?

Xanthomas Signup and view all the answers

Study Notes

Cholesterol

Cholesterol is a major sterol in animal tissues, found in tissues and plasma as free cholesterol or as a storage form, combined with a long-chain fatty acid as cholesteryl ester.
Cholesterol is transported in lipoproteins.
Plasma LDL carries cholesterol into tissues.
Free cholesterol is removed from tissues by plasma high-density lipoprotein and transported to the liver for excretion as bile acids (reverse cholesterol transport).
Cholesterol is nearly 25% of lipids in plasma membranes of some nerve cells, but may be absent in other intracellular membranes.
Cells can regulate cholesterol levels by esterifying excess cholesterol with a fatty acid and storing cholesterol esters in vesicles.
Unesterified cholesterol is transported back to the membrane when needed.
Cholesterol increases membrane packing, which both alters membrane fluidity and maintains membrane integrity.
Cholesterol allows animal cells to change shape and for animals to move.
Cholesterol biosynthesis in hepatocytes is negatively regulated by cholesterol itself, primarily influencing the HMG-CoA reductase reaction.

SREBPs

SREBPs (Sterol Regulatory Element Binding Proteins) activate the cholesterol and fatty acid synthesis program in the liver.
Different SREBPs (SREBP-1c and SREBP-2) preferentially activate genes related to cholesterol and/or fatty acid and triglyceride metabolism.
In the presence of cholesterol or oxysterols, SREBP-Scap is retained in the ER.
In the absence of sterols, SREBP-Scap is loaded into COPII vesicles through interactions with Sec23/24
After transport to the Golgi, SREBP's transcription factor domain is released from the membrane by proteolytic cleavage events (S1P and S2P proteases).

HMG-CoA Reductase (HMGCR)

HMG-CoA reductase is the rate-limiting step in cholesterol synthesis in hepatocytes.
The enzyme is competitively suppressed under normal conditions due to negative feedback regulation by end products like cholesterol and oxysterols.
It plays a crucial role in regulating cholesterol biosynthesis from acetyl-CoA to mevalonate.
HMG-CoA reductase is a target of statins, a class of pharmaceuticals used to reduce cholesterol levels.

Mevalonate Pathway

The mevalonate pathway is also known as the isoprenoid pathway or HMG-CoA reductase pathway and is present in eukaryotes, archaea, and some bacteria.
The pathway produces isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).
These building blocks are used to produce isoprenoids, a diverse class of biomolecules, such as cholesterol, vitamin K, coenzyme Q10, and steroid hormones.

Cholesterol Absorption and Excretion

Cholesterol in the intestine must be incorporated into micelles for absorption in the enterocyte.
Cholesterol is absorbed through NPC1L1 (Niemann-Pick C1-like 1)
Cholesterol esters are hydrolyzed and become free cholesterol to be incorporate into the micelles.
Phytosterols, transported via ABCG5/ABCG8, are also absorbed but can displace cholesterol.
Cholesterol not absorbed is excreted in feces.
Fecal excretion, with no cholesterol oxidative pathways in humans, is the primary route for cholesterol catabolism.
Ezetimibe blocks cholesterol absorption by inhibiting NPC1L1.

Familial Hypercholesterolemia (FH)

FH is a genetic disorder characterized by elevated LDL-C levels.
In most cases (75%), it is due to mutations in the LDLR gene, leading to defective LDL receptor function.
Elevated LDL levels can cause early atherosclerosis.
Homozygous FH (two mutated alleles) is a serious form with very high LDL that presents with severe clinical manifestations and generally requires aggressive management.
Heterozygous FH(one mutated allele) is less severe.

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Description

This quiz explores the role and function of cholesterol in animal tissues, including its transport, regulation, and impact on cell membranes. Learn about the different lipoproteins and the importance of cholesterol in maintaining membrane integrity. Test your knowledge on how cholesterol contributes to cellular shape and animal movement.