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Questions and Answers
What is the primary enzyme responsible for converting Acetoacetate to Beta-hydroxybutyrate?
What is the primary enzyme responsible for converting Acetoacetate to Beta-hydroxybutyrate?
What effect does high levels of malonyl-CoA have on Ketogenesis?
What effect does high levels of malonyl-CoA have on Ketogenesis?
Which condition typically leads to ketoacidosis due to high ketone bodies in the blood?
Which condition typically leads to ketoacidosis due to high ketone bodies in the blood?
In what state is ketogenesis elevated due to increased fatty acid oxidation?
In what state is ketogenesis elevated due to increased fatty acid oxidation?
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Which hormonal change is associated with the stimulation of ketogenesis?
Which hormonal change is associated with the stimulation of ketogenesis?
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What role does glucagon play in the regulation of beta-oxidation during fasting?
What role does glucagon play in the regulation of beta-oxidation during fasting?
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Which factor is the primary inhibitor of CPT I activity?
Which factor is the primary inhibitor of CPT I activity?
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What nutritional state is likely to promote ketogenesis by reducing glucose availability?
What nutritional state is likely to promote ketogenesis by reducing glucose availability?
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Which factor is most likely to inhibit ketogenesis related to the NADH/NAD⁺ ratio?
Which factor is most likely to inhibit ketogenesis related to the NADH/NAD⁺ ratio?
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During which physiological state does beta-oxidation predominantly increase to meet energy demands?
During which physiological state does beta-oxidation predominantly increase to meet energy demands?
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Which type of hyperlipidemia is primarily caused by genetic disorders?
Which type of hyperlipidemia is primarily caused by genetic disorders?
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How do high levels of NADH/FADH₂ affect oxidative metabolism?
How do high levels of NADH/FADH₂ affect oxidative metabolism?
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Which of the following ketone bodies is NOT produced during ketogenesis?
Which of the following ketone bodies is NOT produced during ketogenesis?
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What is the primary source of ketone bodies during prolonged exercise?
What is the primary source of ketone bodies during prolonged exercise?
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What is a key function of ketone bodies when glucose levels are low?
What is a key function of ketone bodies when glucose levels are low?
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Which enzyme catalyzes the condensation of 2 Acetyl-CoA to form Acetoacetyl-CoA in the ketogenesis pathway?
Which enzyme catalyzes the condensation of 2 Acetyl-CoA to form Acetoacetyl-CoA in the ketogenesis pathway?
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What is the primary fate of the amino group in amino acid metabolism?
What is the primary fate of the amino group in amino acid metabolism?
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Which enzyme is responsible for the oxidative deamination of glutamate?
Which enzyme is responsible for the oxidative deamination of glutamate?
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What coenzyme is required for the process of transamination?
What coenzyme is required for the process of transamination?
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Which metabolic pathway involves the conversion of α-ketoglutarate?
Which metabolic pathway involves the conversion of α-ketoglutarate?
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What is produced when amino groups are removed from amino acids during deamination?
What is produced when amino groups are removed from amino acids during deamination?
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Which amino acid is a general acceptor of amino groups during transamination?
Which amino acid is a general acceptor of amino groups during transamination?
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What is the main purpose of the urea cycle?
What is the main purpose of the urea cycle?
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How many distinct enzymes are involved in the synthesis of urea?
How many distinct enzymes are involved in the synthesis of urea?
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What is the end product of the oxidative deamination process?
What is the end product of the oxidative deamination process?
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Where in the body are most amino acids metabolized?
Where in the body are most amino acids metabolized?
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Which enzyme is responsible for the conversion of acyl-CoA to trans-Δ²-enoyl-CoA during the oxidation step?
Which enzyme is responsible for the conversion of acyl-CoA to trans-Δ²-enoyl-CoA during the oxidation step?
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What is the primary product of the thiolysis step in the β-oxidation process?
What is the primary product of the thiolysis step in the β-oxidation process?
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Which molecule is formed as a result of the second oxidation of 3-hydroxyacyl-CoA?
Which molecule is formed as a result of the second oxidation of 3-hydroxyacyl-CoA?
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During hydration, what functional group is introduced to the fatty acid chain?
During hydration, what functional group is introduced to the fatty acid chain?
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What role does FADH₂ play after it is formed during the first oxidation of acyl-CoA?
What role does FADH₂ play after it is formed during the first oxidation of acyl-CoA?
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What is the substrate for the enoyl-CoA hydratase enzyme during the hydration step?
What is the substrate for the enoyl-CoA hydratase enzyme during the hydration step?
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Which step of β-oxidation is critical for preparing the substrate for further reactions?
Which step of β-oxidation is critical for preparing the substrate for further reactions?
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What happens to NAD⁺ during the second oxidation of 3-hydroxyacyl-CoA?
What happens to NAD⁺ during the second oxidation of 3-hydroxyacyl-CoA?
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Which of the following statements about β-oxidation is true?
Which of the following statements about β-oxidation is true?
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What is the significance of introducing a double bond during the first oxidation step?
What is the significance of introducing a double bond during the first oxidation step?
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What is the primary function of the urea cycle?
What is the primary function of the urea cycle?
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Which enzyme acts as the rate-limiting step in the urea cycle?
Which enzyme acts as the rate-limiting step in the urea cycle?
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What compound activates Carbamoyl Phosphate Synthase I (CPS I)?
What compound activates Carbamoyl Phosphate Synthase I (CPS I)?
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What are the primary products of the cleavage of arginosuccinate?
What are the primary products of the cleavage of arginosuccinate?
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Which of the following conditions is characterized by raised levels of ammonia due to enzyme defects?
Which of the following conditions is characterized by raised levels of ammonia due to enzyme defects?
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Which amino acids are classified as exclusively ketogenic?
Which amino acids are classified as exclusively ketogenic?
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What is the role of fumarate in metabolism?
What is the role of fumarate in metabolism?
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What is the primary energy source generated from beta-oxidation of fatty acids?
What is the primary energy source generated from beta-oxidation of fatty acids?
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During which metabolic condition is beta-oxidation most active?
During which metabolic condition is beta-oxidation most active?
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What initiates the transport of fatty acyl-CoA into the mitochondria?
What initiates the transport of fatty acyl-CoA into the mitochondria?
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Which of the following amino acids can be converted into glucose through gluconeogenesis?
Which of the following amino acids can be converted into glucose through gluconeogenesis?
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What product is generated during each cycle of beta-oxidation of fatty acids?
What product is generated during each cycle of beta-oxidation of fatty acids?
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What will high concentrations of ammonia promote in the urea cycle?
What will high concentrations of ammonia promote in the urea cycle?
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Study Notes
Lecture 7: Protein and Lipid Metabolism
- Lecture presented by Dr. Sophie Shi Ling
- Department of Applied Science, School of Science and Technology, Hong Kong Metropolitan University
Class of Biomolecules for Energy
-
Step 1: Production of acetyl-CoA
- Glucose: Converted to pyruvate via glycolysis, then to acetyl-CoA by pyruvate dehydrogenase
- Fatty acids: Converted to acetyl-CoA via β-oxidation
- Amino acids: Converted to acetyl-CoA via oxidation
-
Step 2: Oxidation of acetyl-CoA via TCA cycle
- Generates NADH and FADH2
- Step 3: ATP production from NADH and FADH2 via oxidative phosphorylation
Part I: Protein Metabolism
- Transamination and Deamination
- Fate of Amino Group → Urea Cycle
- Fate of Carbon Skeletons → Glucogenic or Ketogenic
Overview of Protein Metabolism
- Feature of amino acids: All contain amino groups.
- Key step: Lose amino group (deamination), form α-keto acid
- Amino group: Reused or excreted.
- α-keto acid: Oxidized or recycled.
Amino Acid Catabolism
- Most amino acids are metabolized in the liver.
- Amino group is removed as ammonia (NH4+).
- Some ammonia is recycled and used in biosynthesis; excess is excreted.
- Amino acids are deaminated via transamination to generate glutamate and a-ketoacids.
- α-ketoacids enter gluconeogenic or TCA cycle pathways.
- Glutamate is deaminated, producing ammonia and α-ketoglutarate.
- Ammonia enters the urea cycle for clearance from the body.
- α-ketoglutarate enters the TCA cycle for energy production.
Transamination
- Removal of amino groups from amino acids and transfer to keto acids.
- Catalyzed by aminotransferase or transaminase.
- Requires coenzyme pyridoxal phosphate (PLP).
- Found in high concentrations in the liver.
- α-ketoglutarate is a general acceptor of amino group; glutamate is a temporary storage of amino group.
Oxidative Deamination
- Glutamate formed by transamination is deaminated.
- Catalyzed by glutamate dehydrogenase.
- Produce α-ketoglutarate and ammonia (NH4+).
- Ammonia (NH4+) is processed to urea for excretion.
Excreted Fate of Amino Group → Urea Cycle
- Nitrogen of amino acids converted to ammonia (toxic)
- Converted to urea for detoxification.
- Urea synthesized in the liver and transported to kidneys for excretion in urine.
- Urea has two amino groups (NH2).
- Carbon atoms supplied by CO2.
- Urea synthesis is a five-step cyclic process.
Excreted Fate of Amino Group → Urea Cycle - Detailed steps
- Synthesis of carbamoyl phosphate.
- Formation of citrulline.
- Synthesis of arginosuccinate.
- Cleavage of arginosuccinate.
- Formation of Urea.
Significance of Urea Cycle
- Converts toxic NH4+ into harmless urea.
- Maintains nitrogen homeostasis.
- Recycles TCA cycle intermediates.
- Recycles amino acids and keto acids.
- Ornithine is a precursor of prolines and polyamines.
Regulation of Urea Cycle
- The first reaction catalyzed by carbamoyl phosphate synthase I is the rate-limiting reaction.
- CPS I is activated by N-acetylglutamate (NAG).
- The rate of urea synthesis in the liver is correlated with the concentration of N-acetylglutamate.
- High concentrations of arginine increase NAG.
- The urea cycle is regulated in part by the availability of substrates.
Urea Cycle Disorders
- Hyperammonemia: Raised ammonia levels leading to toxicity.
- Caused by metabolic defects associated with the five enzymes.
Reused Fate of Amino Group → Biosynthesis
- Amino acids and nitrogenous compounds
- Urea, proline, etc
Fate of Carbon Skeletons → Gluconeogenesis
- Amino group is removed by transamination.
- Remaining carbon skeleton (α-keto acid) is catabolized by a pathway unique to that acid.
- Glucogenic amino acids: Form intermediates of carbohydrate metabolism, converted to glucose via gluconeogenesis.
- Metabolized to pyruvate or TCA cycle metabolites.
- 13 amino acids are exclusively glucogenic.
Fate of Carbon Skeletons → Ketogenesis
- Ketogenic amino acids: Can be converted to acetoacetyl-CoA or acetyl-CoA; used for the synthesis of ketone bodies, not glucose.
- Enter 1 of 3 metabolic pathways:
- Enter the TCA cycle to produce ATP/energy.
- Ketogenesis (production of ketone bodies).
- Synthesis of fatty acids or cholesterol.
- Two amino acids are exclusively ketogenic.
Glucogenic and Ketogenic Amino Acids
- Metabolized to intermediates of both gluconeogenesis and ketogenesis pathways.
- 5 amino acids are both glucogenic and ketogenic.
Part II: Lipid Metabolism
- Fatty acid oxidation (β-oxidation)
- Metabolism of ketone bodies
Overview of Lipid Metabolism
- Triacylglycerols → Fatty Acids → β-oxidation → Acetyl-CoA → Citric Acid Cycle → Oxidative Phosphorylation → ATP
- Fatty acid synthesis → Membrane lipids → Cholesterol
Fatty Acid Oxidation β-Oxidation
- Definition: Metabolic process breaking down fatty acids to acetyl-CoA, NADH, and FADH2.
- Location: Primarily in mitochondria of liver and muscle tissues.
- Products: Each cycle shortens the fatty acid chain by two carbon atoms; produces one acetyl-CoA, one NADH, and one FADH2 for each cycle.
- Function: Provides significant energy source, especially during fasting, low-carb status, or prolonged exercise.
Process of β-Oxidation
- Activation of Fatty Acids: Fatty acids are converted to fatty acyl-CoA in the cytoplasm using ATP.
- Transport into Mitochondria: Fatty acyl-CoA is transported into mitochondria via the carnitine shuttle.
- Four Main Steps of Beta Oxidation: Oxidation (dehydrogenation), hydration, second oxidation (dehydrogenation), and thiolysis.
Regulation of β-Oxidation
- Substrate Availability: Higher concentrations of free fatty acids promote beta-oxidation.
- Hormonal Regulation: Insulin inhibits beta-oxidation; glucagon stimulates beta-oxidation.
- Enzyme Regulation: CPT I inhibited by malonyl-CoA; controls entry of fatty acids into mitochondria; acyl-CoA synthetase regulated by substrate availability and energy status.
- Energy Status: High NADH/FADH2 inhibits beta-oxidation; high ATP levels inhibit beta-oxidation.
- Nutritional Status: Fasting upregulates beta-oxidation, fed state downregulates.
Ketogenesis Pathway
- Condensation: 2 acetyl-CoA → acetoacetyl-CoA, catalyzed by thiolase.
- Formation of HMG-CoA: Acetoacetyl-CoA → HMG-CoA, catalyzed by HMG-CoA synthase.
- Production of Ketone Bodies: HMG-CoA → acetoacetate; acetoacetate → beta-hydroxybutyrate; acetoacetate → acetone, spontaneously.
- Export and Utilization: Release into bloodstream. Tissues convert ketone bodies back to Acetyl-CoA for energy.
Regulation of Ketogenesis
- Substrate availability: Free fatty acid levels, increased acetyl-CoA from beta-oxidation.
- Hormonal regulation: Insulin inhibits ketogenesis, glucagon stimulates.
- Enzyme regulation: CPT I inhibited by malonyl-CoA, HMG-CoA Synthase is key regulatory enzyme.
- Energy status: High NADH/NAD+ ratio favors beta-hydroxybutyrate conversion. Low ATP/ADP ratio stimulates ketogenesis.
- Nutritional status: fasting upregulates; low-carb diets promotes ketogenesis.
Disorders Associated with Lipid Metabolism
- Hyperlipidemia: Elevated cholesterol and triglycerides in the blood. Primary (genetic) or secondary (related to conditions like diabetes).
- Fatty Liver Disease: Fat accumulation in the liver (NAFLD, unrelated to alcohol; or alcoholic).
- Ketoacidosis: High ketone bodies in the blood often seen in uncontrolled diabetes.
- Lipid Storage Disorders: Gaucher or Fabry disease: accumulation of certain lipids due to enzyme deficiencies.
Lipid Metabolism and Diabetes
- Insulin promotes lipogenesis and inhibits lipolysis.
- Insulin resistance increases lipolysis leading to elevated free fatty acids in the bloodstream.
- Elevated FFAs impair insulin signaling.
- Insulin resistance disrupts the balance between lipid and glucose metabolism.
- Increased risk of NAFLD and diabetic ketoacidosis.
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Description
Explore the essential processes of protein and lipid metabolism in this quiz based on Lecture 7 presented by Dr. Sophie Shi Ling. Dive into the steps involved in the production of acetyl-CoA, TCA cycle oxidation, and ATP generation. Test your understanding of both transamination and deamination processes as well as the metabolic fate of amino acids.
