Harper's Biochemistry Chapter 26 - Cholesterol Synthesis, Transport, & Excretion

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Questions and Answers

What role does insulin play in the regulation of HMG-CoA reductase activity?

Enhancement of glucagon activity

Dominant role in stimulation (correct)

Inhibition of cholesterol synthesis

No effect on lipid metabolism

Which factor is known to phosphorylate and inactivate HMG-CoA reductase?

Glucagon

Thyroid hormone

Cholesterol itself

AMPK (correct)

How does glucagon influence HMG-CoA reductase activity?

It decreases HMG-CoA reductase activity (correct)

It activates HMG-CoA reductase directly

It indirectly increases cholesterol synthesis

It has no relationship with HMG-CoA reductase

What regulates the transcription of HMG-CoA reductase mRNA?

Insulin-induced gene Signup and view all the answers

Which factor inhibits the activity of HMG-CoA reductase?

Cholesterol Signup and view all the answers

What is the main function of the LDL receptor in cholesterol transport?

Mediating endocytosis of LDL into cells Signup and view all the answers

Which hormone is known to increase HMG-CoA reductase activity?

Thyroid hormone Signup and view all the answers

What is the role of SREBPs in cholesterol metabolism?

Regulating gene transcription for cholesterol uptake Signup and view all the answers

Which statement best describes Insig's function in cholesterol synthesis regulation?

It inhibits SREBP activation Signup and view all the answers

What mechanism is involved in the regulation of HMG-CoA reductase through phosphorylation?

Phosphorylation by AMPK and AMPKK Signup and view all the answers

What type of modification can regulate the activity of HMG-CoA reductase aside from transcriptional control?

Posttranslational modification Signup and view all the answers

Which statement regarding cholesterol balance in tissues is accurate?

The balance is modulated by HMG-CoA reductase activity Signup and view all the answers

How does AMP serve as an allosteric modifier in cholesterol metabolism?

It enhances AMPK activity towards HMG-CoA reductase Signup and view all the answers

What effect does dietary cholesterol have on HMG-CoA reductase activity?

Decreases activity Signup and view all the answers

Which of the following statements is true regarding the fate of acetyl-CoA in cholesterol biosynthesis?

It is a precursor for the synthesis of squalene Signup and view all the answers

What impact do bile acids have within the liver regarding cholesterol?

They help regulate cholesterol synthesis Signup and view all the answers

What role might cholesterol and its metabolites have on cellular processes?

Inhibiting transcription factors related to lipid uptake Signup and view all the answers

Which compound is directly synthesized from farnesyl diphosphate through sequential addition of isopentenyl diphosphate residues?

Dolichol Signup and view all the answers

Which enzyme is primarily responsible for converting HMG-CoA to mevalonate in cholesterol biosynthesis?

HMG-CoA reductase Signup and view all the answers

What role does the SREBP protein play in cholesterol metabolism?

It regulates the expression of genes involved in lipid metabolism. Signup and view all the answers

Which lipid is formed from the cyclization of squalene through the action of squalene epoxidase?

Lanosterol Signup and view all the answers

Which of the following mechanisms primarily facilitates the transport of cholesterol within the bloodstream?

Low-density lipoproteins (LDL) Signup and view all the answers

What effect does an increase in intracellular cholesterol have on the transcription of genes involved in cholesterol synthesis?

It inhibits the transcription of these genes. Signup and view all the answers

Which of the following mechanisms contributes to the decrease in intracellular cholesterol concentration?

Efflux of cholesterol to HDL via specific transporters. Signup and view all the answers

How does the protein PCSK9 affect LDL receptor activity?

It targets the receptor for degradation, reducing its recycling. Signup and view all the answers

What is the primary function of the SREBP pathway in cholesterol metabolism?

To inhibit cholesterol synthesis enzymes based on cholesterol levels. Signup and view all the answers

Which factor directly promotes the hydrolysis of cholesteryl esters?

Cholesteryl ester hydrolase. Signup and view all the answers

How do scavenger receptors such as CD36 contribute to cholesterol balance?

They facilitate the uptake of cholesterol-containing lipoproteins. Signup and view all the answers

In what way does esterification of cholesterol contribute to cholesterol homeostasis?

It reduces the amount of free cholesterol in the cell. Signup and view all the answers

What role does increased extracellular cholesterol-rich lipoproteins play in cellular cholesterol dynamics?

They facilitate the uptake of cholesterol into the cell through receptors. Signup and view all the answers

What effect does cholesterol synthesis have on intracellular cholesterol levels, and how is it related to SREBP?

SREBP inhibition reduces cholesterol synthesis when levels are low. Signup and view all the answers

Which transporters are involved in the efflux of cholesterol to HDL?

ABCA1, ABCG1, and SR-B1. Signup and view all the answers

What effect does increased dietary cholesterol intake have on de novo cholesterol synthesis in the liver?

It causes a decrease in synthesis rates. Signup and view all the answers

Which molecule is primarily responsible for activating HMG-CoA reductase?

Insulin Signup and view all the answers

How does AMPK affect HMG-CoA reductase activity?

By phosphorylating and inactivating it. Signup and view all the answers

What is the role of SREBP in cholesterol metabolism?

It stimulates the synthesis of cholesterol and its transport proteins. Signup and view all the answers

What is the role of protein phosphatases in the regulation of HMG-CoA reductase activity?

They phosphorylate HMG-CoA reductase to deactivate it. Signup and view all the answers

What is the primary function of LDL cholesterol in the body?

To transport cholesterol from the liver to peripheral tissues. Signup and view all the answers

What happens to HMG-CoA reductase activity when energy levels in the cell are low?

Its activity decreases due to increased AMPK activity. Signup and view all the answers

Which of the following regulators is most likely to enhance cholesterol biosynthesis?

Insulin Signup and view all the answers

How does glucagon influence cholesterol synthesis?

By inhibiting the synthesis pathway. Signup and view all the answers

What mechanism allows for short-term changes in enzyme activity concerning cholesterol metabolism?

Posttranslational modification of enzymes. Signup and view all the answers

What is the first step in the process of cholesterol synthesis?

Synthesis of mevalonate from acetyl-CoA Signup and view all the answers

Which of the following correctly details a transformation in the cholesterol biosynthetic pathway?

Mevalonate loses CO2 to yield squalene Signup and view all the answers

Which enzyme is specifically targeted by statins in the cholesterol biosynthesis pathway?

HMG-CoA reductase Signup and view all the answers

What compound serves as the source of all carbon atoms in cholesterol?

Acetyl-CoA Signup and view all the answers

In which step of cholesterol synthesis is lanosterol formed?

During the cyclization of squalene Signup and view all the answers

Which statement best describes the role of HMG-CoA in cholesterol synthesis?

It is an intermediate in the synthesis of mevalonate Signup and view all the answers

What byproduct is generated during the conversion of mevalonate to isoprenoid units?

CO2 Signup and view all the answers

What is the primary regulatory step in cholesterol synthesis?

Reduction of HMG-CoA to mevalonate Signup and view all the answers

Which molecule acts as a key intermediate in the synthesis of both cholesterol and other isoprenoid compounds?

Farnesyl diphosphate Signup and view all the answers

What process directly follows the addition of an acetyl-CoA molecule to acetoacetyl-CoA?

Formation of HMG-CoA Signup and view all the answers

Which enzyme is responsible for the conversion of squalene to squalene 2,3-epoxide?

Squalene epoxidase Signup and view all the answers

In what cellular location does the final step of cholesterol synthesis occur?

Endoplasmic reticulum Signup and view all the answers

What is the result of the phosphorylation of mevalonate?

Formation of isopentenyl diphosphate Signup and view all the answers

What compound is synthesized from the combination of two molecules of isopentenyl diphosphate?

Geranyl diphosphate Signup and view all the answers

Which step in cholesterol biosynthesis involves the removal of double bonds and methyl groups?

Formation of 14-desmethyl lanosterol Signup and view all the answers

What initiates the synthesis of cholesterol from acetate?

Condensation of acetyl-CoA molecules Signup and view all the answers

What effect does mevalonate have on HMG-CoA reductase enzyme activity?

It inhibits the enzyme activity Signup and view all the answers

Which protein is involved in the degradation of HMG-CoA reductase?

Insig Signup and view all the answers

How is the transcription of genes related to cholesterol metabolism affected by SREBPs?

SREBPs regulate the transcription of lipid metabolism genes Signup and view all the answers

Which of the following accurately describes a complex interaction in the regulation of HMG-CoA reductase activity in response to cellular energy levels?

High ATP levels lead to activation of AMPK, decreasing HMG-CoA reductase activity. Signup and view all the answers

During which process is cholesterol primarily synthesized in the body?

Cholesterol biosynthesis Signup and view all the answers

What role does insulin have in relation to HMG-CoA reductase?

It induces the expression of Insig Signup and view all the answers

Which mechanism describes how LDL is internalized by cells after binding to its receptor?

Clathrin-coated pits facilitate the endocytosis of LDL after receptor binding. Signup and view all the answers

What regulatory mechanism is involved in posttranslational modifications of HMG-CoA reductase?

Phosphorylation Signup and view all the answers

What role do oxysterols play in the regulation of cholesterol synthesis?

They act as signaling molecules that inhibit cholesterol synthesis. Signup and view all the answers

How do glucagon and glucocorticoids impact HMG-CoA reductase activity?

They promote the phosphorylation and inactivation of HMG-CoA reductase. Signup and view all the answers

What is the impact of increased intracellular cholesterol levels on HMG-CoA reductase activity?

Inhibits its activity Signup and view all the answers

In the context of cholesterol metabolism, what is the significance of AMPK activation?

It phosphorylates HMG-CoA reductase, thus leading to its inactivation. Signup and view all the answers

What is the consequence of the inhibition of the SREBP transcription factor?

Decreased cholesterol uptake Signup and view all the answers

Which metabolic pathway result is influenced by the products of HMG-CoA reductase?

Steroid hormone synthesis Signup and view all the answers

What role do cholesterol metabolites play in the transcription of HMG-CoA reductase mRNA?

They repress mRNA synthesis Signup and view all the answers

What happens to de novo cholesterol synthesis following an increase in dietary cholesterol intake?

It decreases notably, particularly in the liver. Signup and view all the answers

Which of the following best describes the role of AMPK in cholesterol metabolism?

AMPK phosphorylates and inactivates HMG-CoA reductase. Signup and view all the answers

What immediate effect does insulin have on cholesterol metabolism?

It promotes the conversion of HMG-CoA to mevalonate. Signup and view all the answers

Which factor is primarily responsible for the phosphorylation of HMG-CoA reductase, leading to its inactivation?

Glucagon signaling through AMPK. Signup and view all the answers

What describes the relationship between intracellular cholesterol levels and the transcription of HMG-CoA reductase?

Low levels of cholesterol lead to increased transcription of HMG-CoA reductase. Signup and view all the answers

Which statement accurately reflects the process of cholesterol regulation through short-term changes?

Posttranslational modifications can quickly modify enzyme activities. Signup and view all the answers

What is the primary consequence of activating protein phosphatases in cholesterol synthesis?

They inhibit enzyme activity via dephosphorylation. Signup and view all the answers

Which of the following accurately describes the influence of glucagon on cholesterol metabolism?

It aids in the phosphorylation and subsequent inactivation of HMG-CoA reductase. Signup and view all the answers

Which hormone is primarily responsible for the feedback regulation of cholesterol synthetic pathways?

Glucagon, mainly through signaling effects. Signup and view all the answers

What is the role of AMP in the context of energy levels and cholesterol metabolism?

Increased AMP levels indicate low energy, inhibiting cholesterol synthesis. Signup and view all the answers

Match the following lipoproteins with their primary function in cholesterol transport:

Chylomicrons = Transport dietary lipids from the intestines VLDL = Transport endogenous triglycerides and cholesterol LDL = Deliver cholesterol to cells HDL = Carry cholesterol away from tissues Signup and view all the answers

Match the stages of cholesterol biosynthesis with their functions:

Acetyl-CoA = Starting material for synthesis HMG-CoA = Intermediate formed in the pathway Mevalonate = Key intermediate leading to isoprenoid synthesis Squalene = Precursor to cholesterol Signup and view all the answers

Match the bile acids with their description:

Primary bile acids = Synthesized from cholesterol in the liver Secondary bile acids = Produced by intestinal bacteria from primary bile acids Cholic acid = A common primary bile acid Chenodeoxycholic acid = Another primary bile acid found in mammals Signup and view all the answers

Match the following factors with their effect on cholesterol levels:

Dietary cholesterol = Increases cholesterol levels in the blood Exercise = May lower LDL levels Fiber intake = Helps lower cholesterol absorption Saturated fats = Can raise LDL levels Signup and view all the answers

Match the following terms with their definitions:

Enterohepatic circulation = Recycling of bile acids between the intestine and liver Atherosclerosis = Cholesterol build-up in arterial walls Gallstone disease = Formation of stones due to excess cholesterol Cholesterol homeostasis = Regulation of cholesterol levels in the body Signup and view all the answers

Match the following terms with their descriptions in cholesterol biosynthesis:

Acetyl-CoA = Starting material for cholesterol synthesis HMG-CoA synthase = Converts Acetyl-CoA to HMG-CoA Endoplasmic reticulum = Site of cholesterol synthesis within a cell Mevalonate = Intermediate compound in cholesterol biosynthetic pathway Signup and view all the answers

Match the following cholesterol synthesis components with their functions:

Squalene = Precursor to lanosterol Lanosterol = Immediate precursor to cholesterol Farnesyl diphosphate = Source of isoprenoid units Cholesterol = Final product of the biosynthesis pathway Signup and view all the answers

Match the following cells/tissues with their role in cholesterol synthesis:

Liver = Major site for cholesterol synthesis Intestine = Contributes to cholesterol from dietary sources Nucleated cells = Capable of synthesizing cholesterol Adipose tissue = Minimal role in cholesterol production Signup and view all the answers

Match the following statements about cholesterol synthesis with their corresponding facts:

Acetyl-CoA synthesis = Requires thiolase enzyme Endoplasmic reticulum location = Where cholesterol is synthesized Cholesterol intake = Can decrease endogenous cholesterol synthesis Dietary cholesterol's impact = 1970s studies connected with HMG-CoA reductase Signup and view all the answers

Match the following cholesterol biosynthesis intermediates with their output:

Mevalonate = Converted to isoprenoid units HMG-CoA = Converted to mevalonate Lanosterol = Precursor for cholesterol Farnesyl diphosphate = Utilized in the formation of squalene Signup and view all the answers

Study Notes

Cholesterol Synthesis, Transport, & Excretion

Cholesterol is a crucial structural component of cell membranes and a precursor for other steroids.
It plays a role in cholesterol gallstones and atherosclerosis.
Cholesterol biosynthesis occurs in five stages from acetyl-CoA.
3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) regulates cholesterol synthesis.
Cellular cholesterol balance is strictly regulated.
Plasma lipoproteins (chylomicrons, VLDL, LDL, HDL) transport cholesterol between tissues.
Primary bile acids are synthesized from cholesterol in the liver for fat digestion and cholesterol excretion.
Secondary bile acids are produced by intestinal bacteria.
The enterohepatic circulation is vital for bile acid recycling.
Factors like diet and lifestyle influence plasma cholesterol levels and coronary heart risk.
Inherited and non-inherited conditions affect lipoprotein metabolism.

Biomedical Importance

Cholesterol is in tissues and plasma as free cholesterol or combined with fatty acids as cholesteryl esters.
It is a crucial structural component in cell membranes.
Cholesterol is a precursor of other steroids (corticosteroids, sex hormones, bile acids, vitamin D).
It is found in foods of animal origin.

Cholesterol Biosynthesis

About 70% of body cholesterol comes from synthesis, the remainder from diet.
The liver and intestine are major sites of synthesis.
Cholesterol comprises 27 carbon atoms with 4 rings and a side chain, derived from acetyl-CoA.
Mevalonate is formed in 5 steps.
Isoprenoid units are formed from mevalonate.
Squalene is formed from 6 isoprenoid units.
Squalene cyclizes to form lanosterol.
Lanosterol is then converted to cholesterol.

Control of Cholesterol Synthesis

HMG-CoA reductase governs cholesterol synthesis.
Regulation involves modulation of enzyme protein synthesis as well as post-translational modification.
Cholesterol and metabolites inhibit HMG-CoA reductase mRNA transcription.
Sterol regulatory element-binding protein (SREBP) activation is involved.
Insulin-induced gene (Insig) is a protein promoting HMG-CoA reductase degradation.

Cholesterol in Tissues

Tight balance maintains intracellular cholesterol levels.
Factors increasing cholesterol: Uptake of lipoprotein with receptors (LDL), uptake of free cholesterol, cholesterol synthesis, and cholesteryl ester hydrolysis.
Factors decreasing cholesterol: Cholesterol efflux to HDL (ABCA1, ABCG1, SR-B1), cholesteryl ester formation (ACAT), and utilization in steroid synthesis/bile acids.

Cholesterol Transport

Cholesterol is transported in lipoproteins (LDL, VLDL, etc.)
Dietary cholesterol is absorbed and esterified.
Cholesterol is delivered to tissues through lipoproteins.
In humans, the majority of plasma cholesteryl ester is caused by lecithin:cholesterol acyltransferase (LCAT).
Cholesterol esters are transferred between lipoproteins by the action of cholesteryl ester transfer protein.

Cholesterol Excretion

Cholesterol is excreted through bile as cholesterol or bile acids.
Primary bile acids (cholic acid and chenodeoxycholic acid) are synthesized in the liver from cholesterol.
Secondary bile acids (deoxycholic acid and lithocholic acid) are formed in the intestine.
The enterohepatic circulation is significant in bile acid recycling.

Clinical Aspects

Serum cholesterol is related to atherosclerosis and coronary heart disease.
Elevated cholesterol levels are a primary factor contributing to atherosclerosis.
Diets high in saturated fat raise serum cholesterol.
Diets rich in polyunsaturated and monounsaturated fats lower serum cholesterol levels.
Lifestyle factors like high blood pressure, smoking, obesity, and lack of exercise are important coronary risk factors.

Disorders of Lipoprotein Metabolism (Dyslipoproteinemias)

Inherited and acquired defects in lipoprotein metabolism can lead to primary or secondary conditions.
Examples of disorders include familial hypercholesterolemia.

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Description

Test your knowledge of cholesterol synthesis, transport, and excretion. This quiz covers essential topics, including the role of cholesterol in cell membranes, its biosynthesis, and the impact of diet and lifestyle on cholesterol levels. Understand the significance of lipoproteins and bile acids in cholesterol metabolism.