Cholesterol Structure and Function
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Questions and Answers

What role does high-density lipoprotein (HDL) play in cholesterol transport?

  • It transports free cholesterol to the liver for excretion. (correct)
  • It decreases the amount of cholesterol released from tissues.
  • It carries cholesterol to tissues.
  • It increases the production of cholesteryl esters.

    • Cholesterol is included in cell membranes primarily to:

  • Increase membrane packing and alter fluidity. (correct)
  • Allow for cell wall formation.
  • Provide rigidity to the membrane structure.
  • Store energy in lipid droplets.

    • Which of the following statements about cholesterol esters is true?

  • They are synthesized when unesterified cholesterol is in excess. (correct)
  • They are exclusively stored in the liver.
  • They are the primary form of cholesterol in plasma membranes.
  • They directly contribute to membrane fluidity.

    • The major sterol found in animal tissues is:

    <p>Cholesterol</p> Signup and view all the answers

    What is the primary function of SREBPs in relation to cholesterol?

    <p>They activate the synthesis of cholesterol and fatty acids in the liver.</p> Signup and view all the answers

    How does unesterified cholesterol interact with phospholipid membranes?

    <p>It maintains membrane integrity by orienting its hydrophobic chain.</p> Signup and view all the answers

    Which of the following statements about the distribution of cholesterol in cells is accurate?

    <p>Some nerve cells contain nearly 25% cholesterol in their plasma membranes.</p> Signup and view all the answers

    What happens to excess cholesterol in cells?

    <p>It is esterified with a fatty acid and stored.</p> Signup and view all the answers

    What is the primary function of the NH2-terminal domain of SREBPs once it enters the nucleus?

    <p>To activate genes required for cholesterol synthesis</p> Signup and view all the answers

    How does the accumulation of cholesterol in the ER affect Scap?

    <p>It induces a conformational change in Scap</p> Signup and view all the answers

    Which enzyme is a primary target for statin drugs due to its role in cholesterol synthesis?

    <p>HMG-CoA reductase</p> Signup and view all the answers

    What effect do oxysterols have on HMG-CoA reductase activity?

    <p>They inhibit the enzyme's activity</p> Signup and view all the answers

    Which metabolic pathway is also known as the isoprenoid pathway?

    <p>Mevalonate pathway</p> Signup and view all the answers

    What triggers the activation of AMPK, leading to inhibition of HMG-CoA reductase?

    <p>Low ATP levels</p> Signup and view all the answers

    What is the rate-limiting step in cholesterol synthesis?

    <p>Conversion of HMG-CoA to mevalonate</p> Signup and view all the answers

    What role does Insig-1 play in the regulation of cholesterol synthesis?

    <p>It stabilizes Scap to prevent complex incorporation into vesicles</p> Signup and view all the answers

    What does SREBP-2 primarily activate in vivo?

    <p>Genes of cholesterol metabolism</p> Signup and view all the answers

    Which proteases mediate the proteolytic cleavage of SREBP in the Golgi?

    <p>S1P and S2P</p> Signup and view all the answers

    How does cholesterol influence the transport of SREBPs?

    <p>By enhancing the binding between Insig and Scap</p> Signup and view all the answers

    What happens to Insig-1 in cells that are depleted of cholesterol?

    <p>It dissociates from Scap and is degraded</p> Signup and view all the answers

    Which target genes are activated by the nuclear form of SREBP?

    <p>HMG-CoA reductase and LDL receptor</p> Signup and view all the answers

    Which SREBP isoform activates genes primarily related to fatty acid and triglyceride metabolism?

    <p>SREBP-1c</p> Signup and view all the answers

    What is the function of the SRE sequence in gene promoters?

    <p>It binds the nuclear form of SREBP to activate genes</p> Signup and view all the answers

    What is indicated by the presence of cholesterol or oxysterols in relation to SREBP-Scap?

    <p>SREBP-Scap is retained in the ER by binding to Insig</p> Signup and view all the answers

    What is the primary function of the hydrophilic C-terminal domain of HMG CoA reductase?

    <p>To exhibit all of the enzyme's catalytic activity</p> Signup and view all the answers

    Which residues in HMG CoA reductase are highlighted as sites for sterol-regulated ubiquitination?

    <p>Lysine residues</p> Signup and view all the answers

    What role do oxysterols play in the regulation of HMG CoA reductase?

    <p>They stimulate its proteasomal degradation</p> Signup and view all the answers

    What is a key purpose of bile acids in the digestive system?

    <p>To emulsify dietary lipids for digestion</p> Signup and view all the answers

    After bile salts are secreted into the small intestine, what happens to them?

    <p>They undergo dehydroxylation by bacteria.</p> Signup and view all the answers

    Which bile acids are synthesized by the liver?

    <p>Cholic acid and chenodeoxycholic acid</p> Signup and view all the answers

    What distinguishes primary bile salts from secondary bile salts?

    <p>Primary bile salts are conjugated with taurine or glycine.</p> Signup and view all the answers

    What happens to cholesterol in food during digestion?

    <p>It is esterified with a fatty acid.</p> Signup and view all the answers

    What is the primary reason phytosterols reduce cholesterol absorption?

    <p>They displace cholesterol from micelles.</p> Signup and view all the answers

    Which protein mediates the uptake of cholesterol in enterocytes?

    <p>Niemann-Pick C1 like 1.</p> Signup and view all the answers

    How much cholesterol is contributed by dietary intake per day?

    <p>300 mg.</p> Signup and view all the answers

    What role does cholesterol esterase play in cholesterol metabolism?

    <p>It hydrolyzes cholesterol esters to free cholesterol.</p> Signup and view all the answers

    What is the total amount of cholesterol contributed by bile daily?

    <p>Approximately 800–1,400 mg/day.</p> Signup and view all the answers

    What happens to cholesterol that is not absorbed in the intestine?

    <p>It is excreted in feces.</p> Signup and view all the answers

    What is the role of acyl-CoA:cholesterol acyltransferase 2 (ACAT2) in cholesterol metabolism?

    <p>It esterifies cholesterol for chylomicron formation.</p> Signup and view all the answers

    What is the main route for cholesterol catabolism in humans?

    <p>Fecal excretion.</p> Signup and view all the answers

    What is the genetic inheritance pattern of familial hypercholesterolemia (FH)?

    <p>Autosomal dominant</p> Signup and view all the answers

    Which of the following statements is true regarding LDL receptor mutations in patients with familial hypercholesterolemia?

    <p>More than 75% of cases involve defective LDL receptors.</p> Signup and view all the answers

    What is the typical prevalence of heterozygous familial hypercholesterolemia based on genetic studies?

    <p>1 in 220</p> Signup and view all the answers

    What is a common characteristic of cholesterol levels in adults with familial hypercholesterolemia?

    <p>LDL levels over 190 mg/dL</p> Signup and view all the answers

    What is the frequency of homozygous familial hypercholesterolemia in the population?

    <p>1 in 300,000</p> Signup and view all the answers

    What cholesterol level is considered elevated for children with familial hypercholesterolemia?

    <p>Over 160 mg/dL</p> Signup and view all the answers

    How do patients with heterozygous familial hypercholesterolemia typically inherit their condition?

    <p>From one parent with one normal allele and one mutated allele</p> Signup and view all the answers

    What impact do HMG-CoA reductase measurements have on understanding cholesterol metabolism?

    <p>They help assess LDL receptor functionality and genetic mutations.</p> Signup and view all the answers

    Study Notes

    Cholesterol

    • Cholesterol is a major sterol in animal tissues
    • Found in tissues and plasma, either free or combined with fatty acids as cholesteryl esters
    • Transported in lipoproteins, including LDL and HDL
      • LDL carries cholesterol to tissues
      • HDL removes cholesterol from tissues and carries it to the liver
    • Liver excretes cholesterol as bile acids through reverse cholesterol transport

    Cholesterol Structure and Function

    • Cholesterol is a steroid
    • Crucial for membrane structure and fluidity
    • Necessary for synthesis of steroid hormones, bile acids, and vitamin D
    • Can be stored as cholesterol esters in cells

    Cholesterol Synthesis

    • SREBPs regulate cholesterol and fatty acid synthesis in the liver
    • The rate limiting step in cholesterol synthesis is catalyzed by HMG-CoA reductase
    • Cholesterol inhibits HMG-CoA reductase, a negative feedback regulation
    • Regulated by NADPH
    • Cholesterol levels regulate expression of genes involved in cholesterol synthesis

    Sterol-Regulated Membrane Transport and Protein Structure

    • Proteins like HMG-CoA reductase anchor in ER membrane thanks to membrane-spanning regions
    • Sterol sensing in these membrane proteins is critical
    • Lysine sites in the sterol-sensing domains of these proteins are subject to sterol regulation
    • These regulatory mechanisms are critical to cellular cholesterol homeostasis

    Regulation of Cholesterol Synthesis

    • HMG-CoA reductase is the rate limiting step, regulated by
      • Regulation of the enzyme's activity
        • Regulated by insulin and glucagon
        • Regulated by oxysterols, which accumulate when cholesterol concentrations are high
    • Regulation of the enzyme's protein levels
      • Proteasomal degradation is a key mechanism

    Cholesterol Absorption and Excretion

    • Cholesterol is absorbed in the intestine via NPC1L1 transporter
    • Phytosterols also absorbed by NPC1L1, but preferentially excreted by ABCG5/G8 transporters
    • Cholesterol not absorbed is excreted in feces
    • Bile salts play a role in the absorption of dietary cholesterol.

    Familial Hypercholesterolemia

    • FH is an inherited disorder characterized by high LDL cholesterol levels
    • Most common form of FH is heterozygous (one mutated, one normal allele)
    • Homozygous FH (both alleles mutated) is rarer but more severe
    • High LDL cholesterol in FH leads to early atherosclerosis and cardiovascular disease

    Cholesterol and Drugs (e.g., Ezetimibe)

    • Ezetimibe directly inhibits NPC1L1 (cholesterol transporter) reducing cholesterol absorption
    • Statins inhibit HMG-CoA reductase, reducing cholesterol synthesis

    Cholesterol in the diet

    • Approximately 10% of cholesterol in egg yolks and 50% in meat and poultry is esterified
    • Cholesterol esters are absorbed more slowly than free cholesterol
    • Phytosterols are structurally similar to cholesterol and compete for absorption
    • Dietary cholesterol intake is approximately 300 mg/day, bile contributes 800–1400 mg/day

    Cholesterol in the body.

    • Cholesterol is essential for maintaining cellular membrane integrity and function
    • Important for the synthesis of steroid hormones
    • Plays an important role in brain function and nerve conduction

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    Week 5 Lecture 8 Cholesterol PDF

    Description

    This quiz explores the structure, function, and synthesis of cholesterol, a vital sterol in animal tissues. It covers key concepts such as lipoprotein transport, the role of the liver, and the regulatory mechanisms involved in cholesterol metabolism. Test your knowledge on how cholesterol impacts membrane fluidity and steroid hormone synthesis.

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