L3 Ethanol Metabolism
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Questions and Answers

What condition is caused by increased accumulation of bilirubin in the blood due to liver dysfunction?

  • Jaundice (correct)
  • Cirrhosis
  • Hepatitis
  • Ascites

    • Which metabolic function decreases as liver function deteriorates?

  • Synthesis of digestive enzymes
  • Incorporation of amino groups into urea (correct)
  • Production of bile acids
  • Storage of glucose as glycogen

    • What form of liver fibrosis is characterized by a shrunken liver and loss of function?

  • Portal hypertension
  • Steatosis
  • Hepatic carcinoma
  • Laennec cirrhosis (correct)

    • What substance is primarily responsible for the toxicity associated with methanol exposure?

    <p>Formic acid</p> Signup and view all the answers

    Which statement best reflects the findings from the global study on alcohol consumption?

    <p>No level of alcohol consumption is considered safe.</p> Signup and view all the answers

    What is the primary mechanism of visual impairment in methanol toxicity?

    <p>Inhibition of mitochondrial function in the optic nerve</p> Signup and view all the answers

    Which of the following liver functions is decreased in a patient with cirrhosis?

    <p>Conjugation and excretion of bilirubin</p> Signup and view all the answers

    What effect does formic acid have on mitochondrial respiration?

    <p>Inhibits cytochrome c oxidase activity</p> Signup and view all the answers

    Which enzyme is primarily responsible for oxidizing ethanol to acetaldehyde in the liver?

    <p>Alcohol dehydrogenase (ADH)</p> Signup and view all the answers

    What is the primary metabolic byproduct of ethanol after it is oxidized by alcohol dehydrogenase?

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

    Which of the following statements is true regarding the energy yield from the metabolism of ethanol?

    <p>It yields 7 kcal/gram.</p> Signup and view all the answers

    Where does the conversion of acetaldehyde to acetate primarily occur?

    <p>In the mitochondria</p> Signup and view all the answers

    Which pathway is least involved in the metabolism of ethanol?

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

    Which compound is toxic and produced during ethanol metabolism?

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

    What effect does chronic ingestion of ethanol have on lipid transport mechanisms in the body?

    <p>Increased levels of LDL</p> Signup and view all the answers

    Which enzyme depends on NAD+ for its function in ethanol metabolism?

    <p>Alcohol dehydrogenase (ADH)</p> Signup and view all the answers

    What is a consequence of increased NADH/NAD+ ratio in relation to lactate?

    <p>It promotes the formation of lactate.</p> Signup and view all the answers

    Which compound is primarily formed from the metabolism of ethanol that can cause liver damage?

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

    What effect does chronic ethanol abuse primarily have on liver function?

    <p>It causes fatty liver and fibrosis.</p> Signup and view all the answers

    How does acetaldehyde impact glutathione in the liver?

    <p>It binds to glutathione, impairing free radical elimination.</p> Signup and view all the answers

    What major risk factor is associated with increased free radical formation during ethanol metabolism?

    <p>CYP2E1 activity.</p> Signup and view all the answers

    What symptom indicates the beginning of irreversible liver injury in chronic ethanol abuse?

    <p>Hepatic cirrhosis.</p> Signup and view all the answers

    Why does hypoglycemia result from the high NADH/NAD+ ratio?

    <p>It inhibits gluconeogenic precursors from entering the pathway.</p> Signup and view all the answers

    What is the main source of lactate from the metabolism of amino acids during ethanol consumption?

    <p>Alanine.</p> Signup and view all the answers

    What effect do ADH1B and ADH1C alleles have on alcoholism risk?

    <p>They provide a protective effect against the risk of alcoholism.</p> Signup and view all the answers

    Which statement is true about the ALDH2*2 allele?

    <p>Homozygosity for this allele provides absolute protection against alcoholism.</p> Signup and view all the answers

    What is the primary function of disulfiram (Antabuse) in treating alcohol use disorder?

    <p>It inhibits ALDH, thus blocking acetaldehyde conversion.</p> Signup and view all the answers

    What does chronic alcohol consumption do to CYP2E1 and acetaldehyde production?

    <p>It induces CYP2E1, increasing acetaldehyde production.</p> Signup and view all the answers

    What is the impact of having a high Km value for an enzyme like ALDH2?

    <p>It indicates a low activity in metabolizing its substrate.</p> Signup and view all the answers

    Why does the MEOS system contribute to higher acetaldehyde levels during chronic alcohol consumption?

    <p>It produces acetaldehyde more quickly than ALDH can metabolize it.</p> Signup and view all the answers

    Which of the following best describes the metabolism of alcohol in the liver?

    <p>The majority of acetaldehyde is metabolized by ALDH in the liver.</p> Signup and view all the answers

    What type of drug is disulfiram categorized as?

    <p>An irreversible inhibitor of ALDH.</p> Signup and view all the answers

    What is one major consequence of the high NADH/NAD+ ratio resulting from ethanol metabolism?

    <p>Inhibition of the TCA cycle</p> Signup and view all the answers

    Which of the following is NOT an acute effect of ethanol metabolism on lipid metabolism in the liver?

    <p>Inhibition of ketogenesis</p> Signup and view all the answers

    What might result from the accumulation of acetyl CoA in the liver due to chronic ethanol consumption?

    <p>Enhanced lactic acid production</p> Signup and view all the answers

    How does the metabolism of ethanol lead to lactic acidosis?

    <p>By favoring the formation of lactate</p> Signup and view all the answers

    What role does glycerol 3-phosphate play in the context of ethanol metabolism?

    <p>Product of increased DHAP levels</p> Signup and view all the answers

    What is a potential impact of increased acetate production on muscle during ethanol metabolism?

    <p>Enhanced preference for acetate as fuel</p> Signup and view all the answers

    The inhibition of fatty acid oxidation during acute ethanol metabolism contributes to which condition?

    <p>Fatty liver disease</p> Signup and view all the answers

    Which substance is primarily responsible for nausea and vomiting during acute ethanol toxicity?

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

    What is a consequence of the accumulation of ammonia in the blood due to liver dysfunction?

    <p>Potentially toxic levels affecting the brain</p> Signup and view all the answers

    What is the primary characteristic of Laennec cirrhosis?

    <p>Shunken liver with loss of function</p> Signup and view all the answers

    Which of the following best describes the findings of the Global Burden of Diseases study on alcohol consumption?

    <p>No level of alcohol consumption is considered safe</p> Signup and view all the answers

    What is the main toxic compound produced from the metabolism of methanol?

    <p>Formic acid</p> Signup and view all the answers

    What severe effect can result from methanol toxicity due to the accumulation of formic acid?

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

    What happens to bilirubin levels in a patient with cirrhosis?

    <p>Bilirubin accumulates in the blood</p> Signup and view all the answers

    Which symptoms are indicative of a patient experiencing jaundice?

    <p>Visible yellowing of skin and eyes</p> Signup and view all the answers

    How does formic acid affect mitochondrial function?

    <p>It inhibits oxidative phosphorylation</p> Signup and view all the answers

    What is the primary toxic product formed during the metabolism of ethanol?

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

    Which location is primarily responsible for the metabolism of ethanol in the body?

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

    What is the energy yield from the metabolism of ethanol?

    <p>7 kcal/gram</p> Signup and view all the answers

    Which enzyme is involved in converting acetaldehyde to acetate?

    <p>Acetaldehyde dehydrogenase (ALDH)</p> Signup and view all the answers

    How does ethanol metabolism affect normal human metabolism?

    <p>Decreases fatty acid oxidation</p> Signup and view all the answers

    What is the role of NAD+ in ethanol metabolism?

    <p>It acts as a substrate for alcohol dehydrogenase.</p> Signup and view all the answers

    What effect does chronic alcohol ingestion have on the NADH/NAD+ ratio?

    <p>It elevates the NADH/NAD+ ratio.</p> Signup and view all the answers

    What is a consequence of acetate metabolism in muscles?

    <p>Increased oxidation in the TCA cycle</p> Signup and view all the answers

    Which of the following metabolic changes is a consequence of chronic ethanol consumption?

    <p>Inhibition of the TCA cycle</p> Signup and view all the answers

    What is one of the acute effects of ethanol metabolism on fatty acid metabolism in the liver?

    <p>Increased production of ketone bodies</p> Signup and view all the answers

    Which condition can result from the accumulation of acetaldehyde during acute ethanol consumption?

    <p>Nausea and vomiting</p> Signup and view all the answers

    What effect does a high NADH/NAD+ ratio have on lactate levels?

    <p>Promotes lactate formation</p> Signup and view all the answers

    How does ethanol metabolism affect the production of acetyl CoA?

    <p>It promotes the direction of acetyl CoA towards ketogenesis</p> Signup and view all the answers

    What adverse effect can result from increased blood levels of acetate due to ethanol metabolism?

    <p>Inhibition of acetate utilization by muscles</p> Signup and view all the answers

    What is the result of the high NADH/NAD+ ratio on fatty acids in the liver?

    <p>Accumulation of fatty acids occurs</p> Signup and view all the answers

    What is a long-term consequence of chronic ethanol abuse on liver function?

    <p>Development of cirrhosis</p> Signup and view all the answers

    What is a consequence of the accumulation of acetaldehyde in the liver after heavy ethanol consumption?

    <p>Formation of covalent adducts with cellular components</p> Signup and view all the answers

    Which metabolic precursor is inhibited from entering gluconeogenesis due to a high NADH/NAD+ ratio?

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

    What condition can result from chronic ethanol abuse due to hepatocellular damage?

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

    Elevated levels of which substance can lead to decreased uric acid excretion and potentially cause gout?

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

    How does acetaldehyde affect protein synthesis in the liver?

    <p>Decreases protein synthesis</p> Signup and view all the answers

    What persistently elevated ratio can lead to inhibition of glycolysis and symptom of hypoglycemia?

    <p>NADH/NAD+</p> Signup and view all the answers

    What is the primary cause of fatty liver in chronic ethanol consumers?

    <p>Accumulation of VLDL due to microtubule damage</p> Signup and view all the answers

    What effect does chronic ethanol consumption have on mitochondrial function?

    <p>It causes mitochondrial damage</p> Signup and view all the answers

    Which alleles of ADH are associated with a protective effect against alcoholism?

    <p>ADH1B and ADH1C</p> Signup and view all the answers

    What is the effect of homozygosity for the ALDH2*2 allele on alcoholism risk?

    <p>It provides absolute protection against alcoholism.</p> Signup and view all the answers

    How does disulfiram (Antabuse) function as a treatment for alcohol use disorder?

    <p>It blocks the conversion of acetaldehyde to acetate.</p> Signup and view all the answers

    What occurs due to the induction of CYP2E1 during chronic alcohol consumption?

    <p>Faster accumulation of acetaldehyde.</p> Signup and view all the answers

    What is the primary substrate metabolized by ALDH in the liver?

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

    Which characteristic of ALDH2*2 allele contributes to its ineffectiveness?

    <p>High Km for acetaldehyde.</p> Signup and view all the answers

    What is one consequence of the high Km value for CYP2E1 in terms of ethanol oxidation?

    <p>It functions only at high ethanol concentrations.</p> Signup and view all the answers

    Which statement about the MEOS system is true?

    <p>It becomes more active during chronic alcohol consumption.</p> Signup and view all the answers

    Study Notes

    Metabolism of Ethanol

    • Ethanol is not stored in the body
    • About 2-10% is excreted renally or pulmonarily
    • The primary method for removing ethanol from the body is through metabolism.
    • Ethanol metabolism releases 7 kcal/gram of energy.
    • Major sites for ethanol metabolism are the liver (ADH and MEOS)
    • Lesser sites include gastric mucosa, kidneys, lungs, and small intestine.

    Learning Goals

    • Understand the steps of ethanol metabolism in the human body, including energy yield, distribution, cellular location, genetic variations of enzymes.
    • Describe effects of ethanol on liver energy metabolism.
    • Define the molecular mechanisms of ethanol's acute and chronic toxicity on human metabolism, taking into consideration gluconeogenesis, fatty acid metabolism, ketogenesis, acid-base imbalances, and lipid transport.
    • Understand the effects of ethanol on lactic acid and ketoacidosis.
    • Analyze the mechanism of action for disulfiram in the treatment of chronic alcoholism.
    • Explain the role of alcohol dehydrogenase (ADH) and alcohol dehydrogenase-like enzymes (ALDH), as well as Microsomal Ethanol Oxidizing System (MEOS).

    Pathways of Ethanol Metabolism

    • Alcohol dehydrogenase (ADH) oxidizes ethanol to acetaldehyde in the cytoplasm of hepatocytes.
    • Acetaldehyde dehydrogenase (ALDH) oxidizes acetaldehyde to acetate in mitochondria.
    • Acetaldehyde is toxic, whereas acetate is not.
    • Both ADH and ALDH are NAD+ dependent.

    Metabolic Fate of Acetate

    • Most acetate enters the bloodstream, is absorbed by skeletal muscle, and converted into acetyl CoA—which further enters the TCA cycle for energy generation.

    Genetic Variations

    • Both ADH and ALDH genes have multiple variants (alleles).
    • Genetic variations in ADH and ALDH affect the speed of ethanol metabolism, impacting the risk of alcoholism.
    • ADH1B and ADH1C alleles are associated with a rapid conversion of ethanol to acetaldehyde, offering protective effects against alcoholism.
    • ALDH2 *2 alleles are associated with a reduced ability to metabolize acetaldehyde, which can cause adverse symptoms and limit alcohol consumption.

    Microsomal Ethanol Oxidizing System (MEOS)

    • Approximately 10-20% of ethanol is oxidized by MEOS (CYP2E1) in the endoplasmic reticulum.
    • CYP2E1 oxidizes ethanol to acetaldehyde.
    • MEOS functions only at higher ethanol concentrations.
    • MEOS is less efficient than ADH, consuming more NADPH.
    • Chronic alcohol consumption induces the cytochrome p450 enzymes and CYP2E1 transcription.

    Toxic Effects of Ethanol Metabolism

    • Acute effects: nausea, vomiting, fatty liver, ketoacidosis, lactic acidosis, hypoglycemia/hyperglycemia.
    • Chronic effects: fatty liver, hepatitis, cirrhosis (irreversible damage characterized by fibrosis, altered structure/function, and potential failure).
      Ethanol, through acetaldehyde, impacts protein functions, leading to damage and impaired function.

    Methanol Toxicity

    • Adverse effects are primarily due to the accumulation of formic acid.
    • Symptoms may include blindness, acid-base disturbances, and acute kidney injury.
    • The primary mechanism is the interruption of mitochondrial function in the optic nerve, particularly due to the inhibition of cytochrome c oxidase by formate.

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    Description

    Test your knowledge on the metabolism of ethanol in the human body. This quiz covers the biochemical processes, energy yield, and the effects of ethanol on liver metabolism. Understand the implications of ethanol toxicity and treatment mechanisms such as disulfiram.

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