Secondary Carnitine Deficiency and Its Causes
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Questions and Answers

What is the major energy reserve of the body?

  • Dihydroxyacetone phosphate
  • Glycerol 3-phosphate
  • Fatty acyl CoA
  • TAG stored in brown adipocytes (correct)
  • What is the initial acceptor of fatty acids during TAG synthesis?

  • Glycerol 3-phosphate dehydrogenase
  • Dihydroxyacetone phosphate (correct)
  • Glucose transporter in adipocytes
  • Glycerol kinase
  • Which enzyme is responsible for converting free glycerol to glycerol 3-phosphate in the liver?

  • Glycerol 3-phosphate dehydrogenase
  • GLUT-4
  • Fatty acyl CoA synthetase
  • Glycerol kinase (correct)
  • What is required to activate a free fatty acid before it can participate in metabolic processes?

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

    Why do adipocytes have limited ability to synthesize glycerol phosphate when plasma glucose levels are low?

    <p>Insulin activates GLUT-4</p> Signup and view all the answers

    What serves as a source of heat through nonshivering thermogenesis?

    <p>TAG stored in brown adipocytes</p> Signup and view all the answers

    Where does the initial dehydrogenation take place in peroxisomal β-oxidation?

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

    What is the product when FADH2 is oxidized by O2 in peroxisomal β-oxidation?

    <p>Hydrogen peroxide (H2O2)</p> Signup and view all the answers

    In peroxisomal α-oxidation, what makes phytanic acid unsuitable as a substrate for acyl CoA dehydrogenases?

    <p>Methyl group on α-carbon</p> Signup and view all the answers

    Which enzyme catalyzes the initial dehydrogenation in peroxisomal β-oxidation?

    <p>Acyl CoA oxidase</p> Signup and view all the answers

    What genetic defect results in the accumulation of very-long-chain fatty acids (VLCFA) in Zellweger syndrome?

    <p>Inability to target proteins to peroxisomes</p> Signup and view all the answers

    What is the primary cause of secondary carnitine deficiency?

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

    Why is no ATP generated during the step involving FAD-containing acyl CoA oxidase in peroxisomal β-oxidation?

    <p>Uncoupling of oxidative phosphorylation</p> Signup and view all the answers

    Which organ is most affected by CPT-1 deficiency?

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

    In acquired secondary carnitine deficiency, what can lead to the decreased availability of carnitine?

    <p>Taking valproic acid</p> Signup and view all the answers

    What is the effect of CPT-II deficiency in skeletal muscle?

    <p>Muscle weakness with myoglobinemia after exercise</p> Signup and view all the answers

    Why are medium-chain fatty acids especially important for individuals with carnitine deficiencies?

    <p>They do not need malonyl CoA for activation</p> Signup and view all the answers

    What does the 4'-phosphopantetheine-containing acyl carrier protein (ACP) domain do during fatty acid synthesis?

    <p>Carries acyl units on its terminal thiol group for catalysis</p> Signup and view all the answers

    What is the recommended dietary approach for individuals with CPT-II deficiency?

    <p>Avoid fasting and consume a high-carbohydrate, low-fat diet</p> Signup and view all the answers

    What happens to the acetyl group after being transferred from acetyl CoA to the ACP domain?

    <p>It condenses with the malonyl group on ACP</p> Signup and view all the answers

    Which domain is responsible for converting the 3-ketoacyl group to the corresponding saturated acyl group?

    <p>3-Ketoacyl-ACP reductase</p> Signup and view all the answers

    What is the role of the condensing enzyme domain during fatty acid synthesis?

    <p>Adds two carbons from malonyl CoA to acyl acceptors</p> Signup and view all the answers

    What drives the reaction in the 3-Ketoacyl-ACP synthase domain?

    <p>Decarboxylation releasing CO2</p> Signup and view all the answers

    What is necessary for converting the 3-ketoacyl group to a saturated acyl group?

    <p>Dehydration step</p> Signup and view all the answers

    Why are ketone bodies considered important sources of energy for peripheral tissues?

    <p>They are used in proportion to their concentration by extrahepatic tissues.</p> Signup and view all the answers

    What leads to the production of ketone bodies in the liver?

    <p>Elevated hepatic acetyl CoA due to fatty acid oxidation</p> Signup and view all the answers

    How do disorders of fatty acid oxidation typically present?

    <p>With hypoketosis and hypoglycemia</p> Signup and view all the answers

    How do ketone bodies spare glucose during prolonged fasting?

    <p>By being used as an alternative energy source</p> Signup and view all the answers

    What effect does fatty acid oxidation have on pyruvate dehydrogenase activity?

    <p>Inhibits pyruvate dehydrogenase</p> Signup and view all the answers

    What is the primary role of ketone bodies in extrahepatic tissues like skeletal muscle and cardiac muscle?

    <p>To serve as an alternative energy source</p> Signup and view all the answers

    Study Notes

    Fatty Acid Oxidation and Synthesis

    • Oxidation of a double bond at an even-numbered carbon, such as linoleic acid, requires an NADPH-dependent 2,4-dienoyl CoA reductase and an isomerase.
    • Unsaturated fatty acids produce fewer reducing equivalents than saturated fatty acids during oxidation.
    • Peroxisomal β-oxidation is the primary site for fatty acids ≥22 carbons in length, which undergo preliminary β-oxidation before diffusing to mitochondria for further oxidation.

    Peroxisomal β-Oxidation

    • FAD-containing acyl CoA oxidase catalyzes the initial dehydrogenation in peroxisomes, producing FADH2, which is oxidized by O2 to produce hydrogen peroxide (H2O2).
    • No ATP is generated from this step, and catalase reduces H2O2 to H2O.
    • Genetic defects in peroxisomal biogenesis or VLCFA transport lead to accumulation of VLCFA in the blood and tissues.

    Peroxisomal α-Oxidation

    • Branched-chain phytanic acid undergoes α-oxidation, which is not a substrate for acyl CoA dehydrogenases due to the methyl group on its α-carbon.

    Ketone Bodies

    • Ketone bodies are important sources of energy for peripheral tissues, being soluble in aqueous solution and produced in the liver during periods of excess acetyl CoA.
    • They spare glucose, which is particularly important during prolonged periods of fasting.
    • Disorders of fatty acid oxidation present with hypoketosis and hypoglycemia due to decreased acetyl CoA availability.

    Ketone Body Synthesis by the Liver

    • Elevated hepatic acetyl CoA inhibits pyruvate dehydrogenase and activates pyruvate carboxylase, producing OAA for gluconeogenesis rather than the TCA cycle.
    • Fatty acid oxidation decreases the NAD+/NADH ratio, shifting OAA to malate.

    Fatty Acid Synthesis

    • The process involves the addition of two carbons from malonyl CoA to the carboxyl end of a series of acyl acceptors.
    • 4'-Phosphopantetheine, a derivative of pantothenic acid (vitamin B5), carries acyl units on its terminal thiol (-SH) group and presents them to the catalytic domains of FAS during fatty acid synthesis.

    Triglycerol Storage and Function

    • TAG stored in white adipocytes form large oily droplets that are nearly anhydrous, serving as the major energy reserve of the body.
    • TAG stored in brown adipocytes serve as a source of heat through nonshivering thermogenesis.

    Glycerol 3-Phosphate Synthesis

    • Glycerol 3-phosphate is the initial acceptor of fatty acids during TAG synthesis, produced from glucose in the liver and adipose tissue.
    • A second pathway in the liver uses glycerol kinase to convert free glycerol to glycerol 3-phosphate.

    Fatty Acid Activation

    • A free fatty acid must be converted to its activated form (bound to CoA through a thioester link) before participating in metabolic processes such as TAG synthesis, catalyzed by fatty acyl CoA synthetases (thiokinases).

    Carnitine Deficiency

    • Secondary carnitine deficiency occurs primarily due to defects in fatty acid oxidation, leading to the accumulation of acylcarnitines excreted in the urine, decreasing carnitine availability.
    • Defects in CPT-1 and CPT-II can cause mitochondrial oxidation defects, affecting the liver, cardiac, and skeletal muscle.

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    Description

    Learn about secondary carnitine deficiency, which can be a result of defects in fatty acid oxidation, liver disease, medication use, and mitochondrial oxidation. Understand how these factors lead to decreased carnitine availability in the body.

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