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Questions and Answers
What condition is characterized by temporary chest pain that occurs during physical activity?
What condition is characterized by temporary chest pain that occurs during physical activity?
Which symptom is not associated with stable angina?
Which symptom is not associated with stable angina?
What is a common risk factor for the development of atherosclerosis?
What is a common risk factor for the development of atherosclerosis?
What treatment approach is effective for managing symptoms associated with atherosclerosis?
What treatment approach is effective for managing symptoms associated with atherosclerosis?
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Which enzyme is specifically targeted by Statin drugs?
Which enzyme is specifically targeted by Statin drugs?
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What effect does insulin have on HMG-CoA reductase activity?
What effect does insulin have on HMG-CoA reductase activity?
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How does AMPK affect HMG-CoA reductase when cellular energy levels are low?
How does AMPK affect HMG-CoA reductase when cellular energy levels are low?
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What is most likely the initial symptom of coronary artery disease (CAD)?
What is most likely the initial symptom of coronary artery disease (CAD)?
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What is the most common genetic characteristic in patients with familial hypercholesterolemia?
What is the most common genetic characteristic in patients with familial hypercholesterolemia?
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What is the estimated prevalence of heterozygous familial hypercholesterolemia?
What is the estimated prevalence of heterozygous familial hypercholesterolemia?
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Which symptom is associated with familial hypercholesterolemia?
Which symptom is associated with familial hypercholesterolemia?
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What is the frequency of homozygous familial hypercholesterolemia?
What is the frequency of homozygous familial hypercholesterolemia?
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Which apolipoprotein is primarily responsible for LDL binding to cellular receptors?
Which apolipoprotein is primarily responsible for LDL binding to cellular receptors?
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What process occurs when LDL particles are oxidized in the arterial wall?
What process occurs when LDL particles are oxidized in the arterial wall?
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What can happen if the fibrous cap of an atherosclerotic plaque thins and fractures?
What can happen if the fibrous cap of an atherosclerotic plaque thins and fractures?
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Which condition is the most common symptom experienced by patients with familial hypercholesterolemia?
Which condition is the most common symptom experienced by patients with familial hypercholesterolemia?
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What characterizes the N-terminal domain of HMG CoA reductase?
What characterizes the N-terminal domain of HMG CoA reductase?
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In what environment do lysosomal enzymes function optimally?
In what environment do lysosomal enzymes function optimally?
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What is the primary function of lysosomes in a cell?
What is the primary function of lysosomes in a cell?
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Which of the following best describes the role of the YIYF sequence in HMG CoA reductase?
Which of the following best describes the role of the YIYF sequence in HMG CoA reductase?
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What happens when a cell is damaged beyond repair?
What happens when a cell is damaged beyond repair?
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What type of enzymes do lysosomes contain to digest macromolecules?
What type of enzymes do lysosomes contain to digest macromolecules?
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Which category do cathepsin proteases fall into based on their active site amino acid?
Which category do cathepsin proteases fall into based on their active site amino acid?
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How do cells sense cholesterol levels effectively?
How do cells sense cholesterol levels effectively?
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What do late endosomes mature from prior to becoming lysosomes?
What do late endosomes mature from prior to becoming lysosomes?
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Which structure directly forms from preautophagosomal structures?
Which structure directly forms from preautophagosomal structures?
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What mediates the acidification of lysosomes and autolysosomes?
What mediates the acidification of lysosomes and autolysosomes?
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In chaperone-mediated autophagy, which motif is recognized by the chaperone protein complex?
In chaperone-mediated autophagy, which motif is recognized by the chaperone protein complex?
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What type of autophagy involves the formation of a double-membrane autophagosome?
What type of autophagy involves the formation of a double-membrane autophagosome?
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What happens to lysosomes when they fuse with autophagosomes?
What happens to lysosomes when they fuse with autophagosomes?
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Which component serves as a receptor for chaperone-mediated autophagy within the lysosomal lumen?
Which component serves as a receptor for chaperone-mediated autophagy within the lysosomal lumen?
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What is formed when lysosomes fuse with autophagosomes?
What is formed when lysosomes fuse with autophagosomes?
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What is the optimal pH range for the functioning of most lysosomal hydrolases?
What is the optimal pH range for the functioning of most lysosomal hydrolases?
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Which lysosomal hydrolase operates optimally at the lowest end of the lysosomal pH range?
Which lysosomal hydrolase operates optimally at the lowest end of the lysosomal pH range?
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What is the general size of lysosomes in regular eukaryotic cells?
What is the general size of lysosomes in regular eukaryotic cells?
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Which statement accurately describes the role of pH in lysosomal function?
Which statement accurately describes the role of pH in lysosomal function?
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Why is the maintenance of low pH essential for lysosomal function?
Why is the maintenance of low pH essential for lysosomal function?
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Which type of cell is known to lack lysosomes?
Which type of cell is known to lack lysosomes?
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What kind of cellular structure do lysosomes exist as?
What kind of cellular structure do lysosomes exist as?
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Which process involves the introduction of substrates that can cause intraluminal pH rises in lysosomes?
Which process involves the introduction of substrates that can cause intraluminal pH rises in lysosomes?
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Which type of microscope is required to observe lysosomes?
Which type of microscope is required to observe lysosomes?
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What is the main function of the transcription factor TFEB in relation to lysosomes?
What is the main function of the transcription factor TFEB in relation to lysosomes?
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What element does TFEB specifically bind to for gene activation?
What element does TFEB specifically bind to for gene activation?
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Which of the following is a transcriptional target of TFEB?
Which of the following is a transcriptional target of TFEB?
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What role does v-ATPase play in lysosomes under normal conditions?
What role does v-ATPase play in lysosomes under normal conditions?
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What does the Coordinated Lysosomal Expression and Regulation (CLEAR) program regulate?
What does the Coordinated Lysosomal Expression and Regulation (CLEAR) program regulate?
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What is one of the outcomes of TFEB activation on autophagy-related molecules?
What is one of the outcomes of TFEB activation on autophagy-related molecules?
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Which of the following specifically promotes lysosome formation in vitro?
Which of the following specifically promotes lysosome formation in vitro?
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Study Notes
Familial Hypercholesterolemia (FH)
- FH is a genetic disorder characterized by high LDL cholesterol levels.
- Over 75% of FH cases have a defective LDL receptor, caused by mutations in the LDLR gene.
- FH is inherited in an autosomal dominant manner.
- Heterozygous FH affects about 1 in 220 people, with one normal and one mutated LDL receptor allele.
- Homozygous FH is much rarer, affecting about 1 in 300,000. This form is associated with a worse prognosis.
- High LDL cholesterol levels are a primary sign. Symptoms often include early heart disease and heart attacks.
LDL Cholesterol and Atherosclerosis
- LDL (low-density lipoprotein) cholesterol is a major risk factor for atherosclerosis.
- LDL particles can oxidize in the artery wall.
- Oxidized LDL is then taken up by macrophages, forming fatty streaks.
- Fatty streaks develop into atherosclerotic plaques.
- Plaque rupture can cause thrombus formation, leading to heart attacks.
Coronary Artery Disease (CAD) Symptoms
- Stable angina: Chest pain or discomfort, predictable and often triggered by physical activity or stress. Disappears with rest or nitroglycerin.
- Shortness of breath (dyspnea): Some CAD patients experience shortness of breath during light exertion.
- Heart attack symptoms: Chest pain/discomfort, pressure, tightness, aching, fullness; heaviness or pain radiating to the arm, neck, jaw or back; shortness of breath, nausea, sweating, dizziness, lightheadedness, palpitations, or indigestion.
Atherosclerosis
- Atherosclerosis is characterized by patchy intimal plaques within medium and large arteries.
- These plaques contain lipids, inflammatory cells and connective tissue.
- Risk factors for development include: Dyslipidemia, Diabetes, Smoking, Family history, Sedentary lifestyle, Obesity, Hypertension
- Symptoms manifest when plaque growth or rupture reduces or obstructs blood flow.
- Diagnosis is clinical; confirmed with angiography, ultrasonography, or other imaging tests.
HMG-CoA Reductase Regulation
- HMG-CoA reductase is a key enzyme in cholesterol biosynthesis; regulated by multiple pathways.
- Insulin activates the enzyme; Glucagon and oxysterols inhibit it.
- Oxysterols accumulate when cholesterol is abundant. These then inhibit LDL receptor-mediated endocytosis.
- Low cellular ATP leads to activation of AMPK leading to inhibition of HMG-CoA reductase.
Lysosomes
- Lysosomes are membrane-bound organelles specialized for intracellular digestion.
- Contain various hydrolytic enzymes to break down cellular waste (e.g., proteins, lipids, nucleic acids).
- Acidic pH (~5.0) activates the hydrolases.
- Lysosomes also function in removing damaged organelles.
- Lysosomes may play a role in programmed cell death (apoptosis).
Lysosomal Biogenesis Regulation
- TFEB (transcription factor EB): Key player in regulating lysosomal biogenesis and function.
- TFEB activity is influenced by cellular conditions (e.g., nutrient levels, stress).
- Increased TFEB activity leads to increased expression of lysosomal enzymes and lysosome function.
- mTOR (mammalian target of rapamycin) pathway suppresses TFEB, and regulates nutrient sensor activity.
Coordinated Lysosomal Expression and Regulation (CLEAR)
- Cellular mechanism for coordinating the expression of genes involved in the lysosomal pathway.
- Mediated by transcription factor EB (TFEB).
- CLEAR elements are E-box sequences recognized by TFEB, essential for upregulating the lysosome functional pathway.
mTOR and Nutrient Signaling
- mTOR (mammalian target of rapamycin) pathway integrates signals from nutrients or amino acids.
- mTORC1 integrates the nutrients and the energy status.
- Nutrients and energy stores are essential for protein synthesis, cell growth, proliferation, and survival.
- Activation of mTOR supports growth and survival by increasing access to nutrients and metabolic fuels.
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Description
This quiz covers the genetic disorder Familial Hypercholesterolemia (FH) and its link to high LDL cholesterol levels. It explores how LDL cholesterol contributes to atherosclerosis and the development of coronary artery disease. Test your knowledge on the symptoms, causes, and genetic factors influencing these cardiovascular issues.