Eicosanoids and Prostaglandin Synthesis
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Questions and Answers

What are eicosanoids primarily derived from?

  • Omega-3 fatty acids
  • Trans fatty acids
  • Arachidonic acid (correct)
  • Saturated fats

    • Which pathway is responsible for the synthesis of prostaglandins?

  • Lipoxygenase Pathway
  • Cytochrome P450 Pathway
  • Fatty Acid Synthase Pathway
  • Cyclooxygenase Pathway (correct)

    • Which medication type is known to inhibit cyclooxygenase enzymes?

  • Corticosteroids
  • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) (correct)
  • Antibiotics
  • Beta-blockers

    • What effect does chronic inflammation have concerning prostaglandin production?

    <p>Increases prostaglandin production</p> Signup and view all the answers

    What is the approximate half-life of prostaglandins?

    <p>30 seconds</p> Signup and view all the answers

    Which enzyme plays a crucial role in the synthesis of thromboxanes?

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

    What activates the phospholipase enzyme involved in prostaglandin synthesis?

    <p>Epinephrine and angiotensin II</p> Signup and view all the answers

    Which form of cyclooxygenase is indicative of a constitutive role in the body?

    <p>COX-1</p> Signup and view all the answers

    What enzyme catalyzes the initial step of lipolysis in adipose tissue?

    <p>Hormone-sensitive lipase</p> Signup and view all the answers

    Which process converts 15-OH group to keto group in the context of fatty acid metabolism?

    <p>Inactivation by 15-hydroxy-prostaglandin-dehydrogenase</p> Signup and view all the answers

    What is the activated form of long chain free fatty acids called?

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

    What role does glucagon play in the process of lipolysis?

    <p>Stimulates Protein Kinase A</p> Signup and view all the answers

    How are free fatty acids (FFAs) transported in the blood?

    <p>As albumin-bound form</p> Signup and view all the answers

    What initiates the first step of hydrolysis during lipolysis?

    <p>Triacylglycerol Lipase (ATGL)</p> Signup and view all the answers

    What is released during the conversion of FFA to its CoA derivative?

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

    Which enzyme is responsible for hydrolyzing monoacylglycerol to free fatty acids and glycerol?

    <p>Monoacylglycerol Lipase</p> Signup and view all the answers

    What is the first step in the process involving the carnitine shuttle?

    <p>Formation of acylcarnitine from the acyl group and carnitine</p> Signup and view all the answers

    Which enzyme catalyzes the transportation of acylcarnitine into the mitochondrial matrix?

    <p>Carnitine–acylcarnitine translocase</p> Signup and view all the answers

    How does malonyl CoA affect the carnitine shuttle mechanism?

    <p>It inhibits CPT-I activity</p> Signup and view all the answers

    What are the primary dietary sources of carnitine?

    <p>Meat products</p> Signup and view all the answers

    Which statement about carnitine deficiency is true?

    <p>It decreases the ability to metabolize long-chain fatty acids.</p> Signup and view all the answers

    What leads to secondary carnitine deficiency?

    <p>Poor renal absorption of carnitine due to certain medications</p> Signup and view all the answers

    What is a possible consequence of carnitine deficiency during fasting?

    <p>Severe hypoglycemia due to inability to oxidize long-chain fatty acids</p> Signup and view all the answers

    What is one result of defects in fatty acid oxidation related to secondary carnitine deficiency?

    <p>Accumulation of acylcarnitines, which are excreted in urine</p> Signup and view all the answers

    What type of fatty acids can diffuse freely through the inner mitochondrial membrane?

    <p>Short-chain fatty acids</p> Signup and view all the answers

    In the first step of beta-oxidation, which enzyme acts on fatty acyl CoA?

    <p>FAD Linked Dehydrogenase</p> Signup and view all the answers

    How many ATPs are produced when FADH2 is oxidized in the electron transport chain?

    <p>1.5 ATPs</p> Signup and view all the answers

    What is formed after the thiolytic cleavage of beta-keto fatty acyl CoA?

    <p>One molecule of acetyl CoA and a shorter fatty acyl CoA</p> Signup and view all the answers

    What is the ultimate fate of propionyl CoA generated from odd-chain fatty acid oxidation?

    <p>It is rearranged to form succinyl CoA.</p> Signup and view all the answers

    Which vitamin is required for the rearrangement of L-methyl malonyl CoA?

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

    During the enzymatic transformation of D-methyl malonyl CoA, which reaction does not occur?

    <p>Cleavage to form acetyl CoA</p> Signup and view all the answers

    What happens to succinyl CoA after its formation from propionyl CoA?

    <p>It enters the TCA cycle.</p> Signup and view all the answers

    What is a key difference in energy yield between unsaturated and saturated fatty acids?

    <p>Unsaturated fatty acids provide less energy than saturated ones.</p> Signup and view all the answers

    Which enzyme is specifically required for the oxidation of monounsaturated fatty acids?

    <p>3,2-enoyl CoA isomerase</p> Signup and view all the answers

    Which lipid class is crucial for maintaining membrane integrity and acts as a precursor for signaling molecules?

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

    In a state of hyperinsulinemia, which metabolic change promotes fatty acid synthesis?

    <p>Increased pyruvate kinase activity and elevated cytosolic acetyl-CoA levels</p> Signup and view all the answers

    What is the primary role of the citrate shuttle in cellular metabolism?

    <p>Transport of acetyl-CoA from mitochondria to the cytoplasm for fatty acid synthesis</p> Signup and view all the answers

    Which enzyme regulates the rate-limiting step of de novo fatty acid synthesis?

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

    Which condition is primarily associated with elevated plasma levels of long-chain acylcarnitines?

    <p>Carnitine deficiency with fatty acid oxidation impairment</p> Signup and view all the answers

    What additional enzyme is required for the oxidation of polyunsaturated fatty acids?

    <p>NADPH-dependent 2,4-dienoyl CoA reductase</p> Signup and view all the answers

    Study Notes

    Lipid III

    • Topic of the lecture is Lipid III
    • Lecturer is Dr. Menega Ganasen
    • Email address is [email protected]
    • Affiliation: Senior Lecturer, Department of Biochemistry, MAHSA University, Selangor, Malaysia
    • Coordinator (Pre-clinical) Examination Committee, School of Medicine, Faculty of Medicine, MAHSA University

    Learning Outcomes

    • Explain lipid diversity in the human body
    • Describe biosynthesis of fatty acids and eicosanoids and their regulations
    • Describe β-oxidation of fatty acids and its regulations

    PUFA

    • Includes linoleic acid (C18:2), α-linolenic acid (C18:3), and arachidonic acid (C20:4)
    • Omega-3 pathway includes EPA and DHA
    • Omega-6 pathway includes GLA and AA

    Eicosanoids

    • Twenty carbon compounds derived from arachidonic acid
    • Synthesis of prostaglandins and thromboxanes via the cyclooxygenase pathway
    • Synthesis of leukotrienes and lipoxins via the lipoxygenase pathway
    • Synthesis of epoxyeicosatrienoic acids and hydroxyeicosatetraenoic acids via the cytochrome P450 pathway

    Prostaglandin Synthesis

    • Prostaglandins are bioactive lipid compounds derived from arachidonic acid
    • Play a key role in inducing and regulating inflammation
    • Synthesized via the cyclooxygenase (COX) pathway
    • Regulated by Nonsteroidal Anti-inflammatory Drugs (NSAIDs) which inhibit COX enzymes, reducing inflammation, pain, and fever.
    • Excessive or dysregulated prostaglandin production can contribute to chronic inflammatory diseases (arthritis, asthma, inflammatory bowel disease)

    Prostaglandin Regulation

    • Phospholipase (PL) activation by epinephrine, thrombin, angiotensin II, bradykinin and vasopressin.
    • Steroids inhibit PL and prevent arachidonic acid release.
    • Cyclooxygenase (COX) is activated by catecholamines and inhibited by NSAIDs.
    • COX-1 (constitutive) produces prostaglandins mediating gastric, renal and platelet functions
    • COX-2 (inducible) mediates inflammatory responses.
    • Prostaglandins have a short half-life (about 30 seconds)
    • Inactivated by 15-hydroxy-prostaglandin dehydrogenase which converts 15-OH group to keto group.

    Beta Oxidation of Fatty Acid

    • Fatty acid oxidation mainly occurs in the mitochondrial matrix of liver, cardiac muscle, skeletal muscle, and kidneys.
    • Triglycerides are hydrolyzed to free fatty acids and glycerol.
    • Fatty acids are activated to fatty acyl-CoA in the cytosol.
    • Fatty acyl-CoA is transported into the mitochondrial matrix via the carnitine shuttle.
    • Four steps involved in beta-oxidation (FAD-linked dehydrogenase, hydration, NAD+ dependent dehydrogenase, cleavage).
    • Generates Acetyl-CoA, NADH, and FADH2.

    Lipolysis in Adipose Tissue

    • Breakdown of triglycerides (TAGs) in adipose tissue for energy during fasting/exercise.
    • Hormone-sensitive lipase (HSL) is activated by glucagon and epinephrine.
    • Perilipin-1 activates Triacylglycerol lipase ATGL
    • ATGL initiates the first step (TAG to DAG), then HSL converts DAG to MAG. MGL hydrolyzes MAG to FFA and glycerol.

    Fate of Glycerol

    • Glycerol is converted to glycerol-3-phosphate
    • Glycerol-3-phosphate is converted to Dihydroxyacetone phosphate (DHAP) via Glycerol kinase
    • DHAP can enter glycolysis or gluconeogenesis pathways

    Fate of Free Fatty Acid (FFA)

    • FFAs are transported in the blood bound to albumin.
    • Long chain FFAs are converted to fatty acyl-CoA in the cytosol.
    • Fatty acyl-CoA is transported into the mitochondrial matrix via the carnitine shuttle.

    Fate of Short-Chain FFA

    • Short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) can diffuse freely through the inner mitochondrial membrane without carnitine or CPT assistance.

    Beta Oxidation (Steps 1-4) for Fatty Acyl CoA

    • FAD-linked dehydrogenase, Hydration, NAD+ dependent dehydrogenase, and Cleavage steps are part of beta-oxidation. These produce Acetyl-CoA, NADH, and FADH2.

    Beta Oxidation (Odd-Chain FFA)

    • Similar oxidation steps as even chain but Propionyl CoA is formed at the end.
    • Propionyl CoA is carboxylated to D-methylmalonyl CoA, then isomerized to L-methylmalonyl CoA, and finally rearranged to succinyl CoA.
    • Succinyl CoA enters the TCA cycle and ultimately used for gluconeogenesis

    Beta Oxidation (Unsaturated FFA)

    • Monounsaturated fatty acids, like oleic acid, require 3,2-enoyl CoA isomerase.
    • Polyunsaturated fatty acids, such as linoleic acid, require 2,4-dienoyl CoA reductase.

    Brainstorm

    • Questions on metabolic pathways related to type 2 diabetes and lipid metabolism
    • Questions about different lipid classes in maintaining membranes and as signaling molecules.
    • Questions on the primary function of the citrate shuttle
    • Questions about enzyme deficiencies related to fatty acid oxidation and their clinical implications
    • Questions on the impact of NSAIDs on eicosanoid synthesis.
    • Diagram of glucose metabolism during fasting.

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    Description

    This quiz explores the biochemical pathways involved in the synthesis of eicosanoids, particularly prostaglandins and thromboxanes. Test your knowledge on enzyme functions, medication influences, and the effects of inflammation on eicosanoid production.

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