Fatty Acid Catabolism Overview
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Questions and Answers

What is the role of malonyl-CoA in fatty acid metabolism?

  • Inhibits the transport of fatty acids into mitochondria (correct)
  • Promotes the conversion of acetyl-CoA to ketone bodies
  • Stimulates the breakdown of fatty acids in mitochondria
  • Enhances gluconeogenesis in the liver
  • Which of the following statements is true regarding vitamin B12?

  • It is synthesized by microbes. (correct)
  • It is also known as hydroxocobalamin.
  • It is used primarily for energy production.
  • It is synthesized by plants and animals.
  • In which organ are ketone bodies predominantly formed?

  • Heart
  • Kidneys
  • Liver (correct)
  • Lungs
  • What are the main types of ketone bodies produced from acetyl-CoA?

    <p>Acetoacetate, acetone, and β-hydroxybutyrate</p> Signup and view all the answers

    What is the consequence of elevated levels of ketone bodies?

    <p>Ketoacidosis or ketosis</p> Signup and view all the answers

    What is produced at the end of normal β-oxidation of odd-number fatty acids?

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

    Which enzyme is responsible for reducing the trans-2 cis-4 bond in cis-double bond intermediates?

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

    Which coenzyme is essential for the isomerization step in the oxidation of odd-number fatty acids?

    <p>Coenzyme B12</p> Signup and view all the answers

    What is the primary reason for reduced energy output in the oxidation of unsaturated fatty acids compared to saturated ones?

    <p>Fewer ATP are generated due to the need for additional enzymes</p> Signup and view all the answers

    What is the configuration of most naturally occurring unsaturated fatty acids?

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

    What is the primary function of epinephrine in fatty acid metabolism?

    <p>Promote the mobilization of fatty acids from adipose tissue</p> Signup and view all the answers

    What type of bond is typically formed between C-2 and C-3 in β-oxidation intermediates?

    <p>Cis-double bond</p> Signup and view all the answers

    Which of the following fatty acids cannot be oxidized in the mitochondria due to its structure?

    <p>Polyunsaturated fatty acids with more than two double bonds</p> Signup and view all the answers

    What happens to the propionyl-CoA produced from odd-number fatty acids?

    <p>It undergoes further processing to succinyl-CoA</p> Signup and view all the answers

    What problem does the cis configuration present for β-oxidation of unsaturated fatty acids?

    <p>It requires additional reactions to produce viable substrates</p> Signup and view all the answers

    What is the role of ketone bodies in metabolism?

    <p>To serve as an emergency energy source during prolonged fasting</p> Signup and view all the answers

    Which enzyme is crucial for the activation of fatty acids before they can undergo beta-oxidation?

    <p>Fatty acyl-CoA synthetase</p> Signup and view all the answers

    Which blood component is directly linked to lipid transport and is often elevated in conditions like diabetes?

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

    What is the primary alternative fuel used by the body during starvation and untreated diabetes mellitus?

    <p>Ketone bodies</p> Signup and view all the answers

    How does the level of oxaloacetate (OAA) affect the conversion of acetyl-CoA in the liver?

    <p>Low OAA favors ketone body formation over entry into the TCA cycle.</p> Signup and view all the answers

    What condition is caused by untreated diabetes mellitus that leads to an accumulation of ketone bodies?

    <p>Diabetic Ketoacidosis</p> Signup and view all the answers

    What is the effect of glucagon on fatty acid metabolism in the state of untreated diabetes?

    <p>Stimulates β-oxidation</p> Signup and view all the answers

    What happens to the production of ketone bodies during prolonged starvation?

    <p>Production increases sharply</p> Signup and view all the answers

    Which enzyme's absence in the liver is crucial in the utilization of ketone bodies in peripheral tissues?

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

    Which of the following best describes the physiological relevance of chylomicrons?

    <p>They transport dietary lipids from the intestines to other locations in the body.</p> Signup and view all the answers

    What is the main reason behind the overproduction of ketone bodies during starvation?

    <p>Decreased levels of insulin</p> Signup and view all the answers

    What is the primary energy source for hibernating animals and migratory birds?

    <p>Fatty acids</p> Signup and view all the answers

    What is the main component of chylomicrons?

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

    What role does epinephrine play in fat mobilization from adipose tissue?

    <p>It stimulates adenylyl cyclase.</p> Signup and view all the answers

    What is a major consequence of conjugation of fatty acids with CoA in regard to energy metabolism?

    <p>It facilitates transportation into mitochondria.</p> Signup and view all the answers

    What is the total ATP yield from the complete β-oxidation of palmitic acid (C16)?

    <p>129 ATP</p> Signup and view all the answers

    Which of the following components are recognized by receptors on cell surfaces in lipoproteins?

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

    Which of the following molecules serves as a shuttle for fatty acids into mitochondria?

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

    What is the first stage of fatty acid oxidation in mitochondria?

    <p>Sequential β-oxidation to generate acetyl-CoA</p> Signup and view all the answers

    Which type of fatty acids does β-oxidation primarily work with?

    <p>Even-numbered saturated fatty acids</p> Signup and view all the answers

    How is the conjugation of fatty acids to CoA energetically characterized?

    <p>Releases pyrophosphate</p> Signup and view all the answers

    Which of the following statements about the metabolism of glycerol is correct?

    <p>Glycerol is converted into glyceraldehyde 3-phosphate.</p> Signup and view all the answers

    What is the role of PKA during fat mobilization in adipose tissue?

    <p>It phosphorylates perilipin.</p> Signup and view all the answers

    What is the end result of transferring electrons from FADH2 and NADH during fatty acid oxidation?

    <p>CO2 and ATP generation</p> Signup and view all the answers

    Which lipid class is not part of the chylomicron composition?

    <p>Fatty acids</p> Signup and view all the answers

    Study Notes

    Fatty Acid Catabolism Overview

    • Fats are esters of glycerol and fatty acids.
    • Fats are highly reduced, thus have high energy content (~80% of total energy for liver and heart).
    • Fats are hydrophobic and inert, segregating from water; easy to store as lipid droplets without raising osmolarity.
    • Fats are a sole energy source for hibernating animals and migratory birds.

    Digestion, Mobilization, and Transport of Fats

    • Bile salts emulsify dietary fats in the small intestine, forming mixed micelles.
    • Intestinal lipases degrade triacylglycerols.
    • Fatty acids and other breakdown products are taken up by intestinal mucosa and converted to triacylglycerols.
    • Chylomicrons are formed, encapsulating triacylglycerols with cholesterol and apolipoproteins.
    • Chylomicrons transport fats through the lymphatic system and bloodstream to tissues.
    • Lipoprotein lipase converts triacylglycerols in chylomicrons to fatty acids and glycerol, releasing them into cells.

    Structure of Chylomicrons

    • Chylomicrons are 100-500 nm in size.
    • Chylomicrons primarily consist of triacylglycerols (~80%), phospholipids, cholesterol, cholesterol esters, and apolipoproteins (lipid-binding proteins).
    • Different combinations of lipids and proteins create various lipoprotein types, including chylomicrons, VLDL, and HDL.

    Mobilization of Triacylglycerols in Adipose Tissue

    • Binding of epinephrine to adipocyte receptors stimulates adenylyl cyclase.
    • cAMP activates protein kinase A (PKA).
    • PKA phosphorylates perilipin, exposing triacylglycerols to hormone-sensitive lipase (HSL).
    • HSL hydrolyzes triacylglycerols into fatty acids and glycerol.
    • Fatty acids are released and transported by serum albumin to other tissues for energy generation.

    Metabolism of Glycerol

    • Glycerol accounts for ~5% of total fat energy.
    • Glycerol is converted to glyceraldehyde 3-phosphate, entering the glycolytic pathway.
    • All phosphorylated species are negatively charged, trapping them in the cytoplasm.

    Fatty Acid Activation Prior to Oxidation

    • Fatty acid oxidation enzymes are in mitochondrial matrix.
    • Fatty acids must be transported from the cytoplasm to mitochondria and conjugated with CoA.
    • This conjugation is highly exothermic, releasing pyrophosphate, which is further hydrolyzed into two phosphates.

    Fatty Acid Transport into Mitochondria

    • Carnitine acts as a fatty acid shuttle between cytosol and the mitochondrial matrix.
    • Fatty acyl-CoA is converted to fatty acylcarnitine by carnitine acyltransferase I.
    • Fatty acylcarnitine crosses the inner mitochondrial membrane.
    • Fatty acylcarnitine is converted back to fatty acyl-CoA by carnitine acyltransferase II.

    Oxidation of Fatty Acids

    • Fatty acid oxidation (β-oxidation) occurs primarily in mitochondria.
    • It involves sequential cycles of oxidation.
    • Each cycle shortens the fatty acid chain by two carbons, producing one acetyl-CoA, one FADH2, and one NADH.
    • Acetyl-CoA enters the citric acid cycle.
    • FADH2 and NADH contribute electrons to the electron transport chain, generating ATP.

    Stage 1: β-Oxidation of Saturated Fatty Acids

    • Acyl-CoA dehydrogenase oxidizes the fatty acyl-CoA, producing trans-Δ2-enoyl-CoA.
    • Enoyl-CoA hydratase adds water to the double bond.
    • β-hydroxyacyl-CoA dehydrogenase oxidizes the hydroxyl group, producing β-ketoacyl-CoA.
    • β-ketoacyl-CoA thiolase cleaves off a two-carbon acetyl-CoA fragment, regenerating the fatty acyl-CoA for the next cycle.

    β-Oxidation of Saturated Fatty Acids: Energy Balance

    • Complete energy yield from palmitic acid (16 carbons) to acetyl-CoA is ~129 ATP.
    • Calculation involves ATP produced from NADH, FADH2, and acetyl-CoA oxidation in the citric acid cycle.

    Monounsaturated Fatty Acid Oxidation

    • Monounsaturated fatty acids have a cis double bond, requiring an enoyl-CoA isomerase.
    • This intermediate isomerase is required to produce trans-Δ2-enoyl-CoA.
    • The remaining steps of β-oxidation are similar to those of saturated fatty acids.

    Polyunsaturated Fatty Acid Oxidation

    • Polyunsaturated fatty acids have more than one double bond.
    • 2,4-dienoyl-CoA reductase and enoyl-CoA isomerase are required to correctly position the double bonds.
    • The further oxidation process is similar to those in other fatty acid oxidation.

    Mono/Polyunsaturated Fatty Acid Oxidation Summary

    • Most naturally occurring unsaturated fatty acids have the cis configuration.
    • Intermediate products require isomerases and reductases for normal β-oxidation due to the correct positioning of the double bonds.
    • These additional steps lead to less energy production.

    Oxidation of Odd-Number Fatty Acids

    • Odd-number fatty acids produce propionyl-CoA at the final cycle.
    • Propionyl-CoA is converted to succinyl-CoA.
    • Succinyl-CoA enters the citric acid cycle.

    Ketone Bodies - Alternative Fuel to Sugars

    • Acetyl-CoA, produced from fatty acid oxidation, can be converted to ketone bodies (acetoacetate, acetone, β-hydroxybutyrate) in the liver.
    • These ketone bodies are exported to other tissues (e.g., heart, muscle, brain) as an alternative fuel source during conditions with low glucose.

    Ketone Bodies Formation

    • Starvation and uncontrolled diabetes cause excess ketone body production.
    • The liver synthesizes ketone bodies from acetyl-CoA when glucose is low.
    • Ketone bodies are transported to other tissues for energy.

    Regulation of Fatty Acid Oxidation

    • High glucose levels stimulate malonyl-CoA production, inhibiting fatty acid transport into mitochondria.
    • Insulin increases fatty acid synthesis and inhibits breakdown.
    • Glucagon promotes fatty acid mobilization and inhibits synthesis.
    • Malonyl-CoA blocks fatty acid transport into mitochondria, regulating fatty acid oxidation.

    Drugs and Diseases

    • Diseases like diabetes can lead to diabetic ketoacidosis (high ketone bodies in the blood).
    • Hormones (e.g., epinephrine) and vitamins (e.g., vitamin B12) are involved in metabolic processes.
    • Monitoring metabolites (like chylomicrons, VLDL, LDL, HDL, and ketone bodies) helps assess metabolic function.

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