Lipid Metabolism
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All diagrams and pictures used in this power point are only for teaching purposes.

True

What are the main classes of Lipids?

  • Fatty acids
  • Glycerophospholipids
  • Steroids
  • All of the above (correct)
  • Generally, all lipids are associated with what?

  • Fatty acids (correct)
  • Glycerophospholipids
  • Steroids
  • None of the above
  • Lipids are not polymers.

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

    Which of the following are classifications of lipids?

    <p>All of the above</p> Signup and view all the answers

    What is the structural formula of a fatty acid?

    <p>$R-C-OH$</p> Signup and view all the answers

    Saturated fatty acid has no double bond.

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

    Unsaturated fatty acid contains at least one double bond.

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

    Which of the following is an example of short hand notation for an unsaturated fatty acid?

    <p>Both A and B</p> Signup and view all the answers

    Which of the following are types of fatty acids?

    <p>All of the above</p> Signup and view all the answers

    Which of the following is true regarding naturally occurring fatty acids?

    <p>All of the above</p> Signup and view all the answers

    Linoleic acid is an omega-6 unsaturated fatty acid.

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

    Naturally occurring fatty acids are obtained from plant oils and fish oils.

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

    Dietary fats are classified based on the presence or absence of fatty acids.

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

    Saturated fatty acids have a higher melting point than unsaturated fatty acids.

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

    The melting point of a fatty acid _______ as the chain length increases.

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

    Triglycerides are a major form of stored energy in the body.

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

    Which of the following hormones are involved in the release of fatty acids from adipose tissues?

    <p>All of the above</p> Signup and view all the answers

    What makes fatty acids a good energy source?

    <p>All of the above</p> Signup and view all the answers

    What is the location of fatty acid biosynthesis?

    <p>cytosol of the cell</p> Signup and view all the answers

    What are the two major enzymes required for fatty acid synthesis?

    <p>Both A and B</p> Signup and view all the answers

    Acetyl-CoA carboxylase is a reversible reaction.

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

    Fatty acid synthase is made up of individual enzymes.

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

    Fatty acid synthesis requires NADPH.

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

    Fatty acid chains are synthesized simultaneously.

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

    The final product of fatty acid biosynthesis using fatty acid synthase is palmitic acid.

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

    The process in which the number of carbons in a fatty acid chain is increased is known as:

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

    The process by which a double bond is introduced between carbon atoms in a fatty acid chain is known as desaturation.

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

    Animals have the enzymes required to desaturate fatty acids beyond delta-9 (△^9) while plants do not.

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

    Citrate is a negative allosteric regulator of acetyl-CoA carboxylase.

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

    What is the effect of glucagon on acetyl-CoA carboxylase?

    <p>It inactivates acetyl-CoA carboxylase.</p> Signup and view all the answers

    Insulin activates acetyl-CoA carboxylase.

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

    Which of the following describes the two major pathways for the synthesis of glycerol-3-phosphate?

    <p>Glycolysis and the glycerol 3-phosphate dehydrogenase</p> Signup and view all the answers

    The biosynthesis of triacylglycerols (TAGs) and phospholipids share the same initial steps, but they diverge at the level of a phosphatidic acid precursor.

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

    Insulin and glucagon are key regulators of TAG synthesis.

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

    The process of hydrolyzing phospholipids into fatty acids and glycerol occurs in the cytosol.

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

    Prostaglandins are crucial in inflammation, acting as a central signaling molecule for the immune response.

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

    Aspirin and NSAIDs (Non-Steroidal Anti-inflammatory Drugs) can inhibit the production of prostaglandins.

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

    Lipolysis is the breakdown of triacylglycerols into fatty acids and glycerol.

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

    Glycerol can be used for gluconeogenesis.

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

    Fatty acids are oxidized in the mitochondria.

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

    The oxidation of fatty acids is irreversible.

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

    The activated fatty acyl CoA is transported into the mitochondria for oxidation.

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

    Carnitine acyltransferase I is inhibited by malonyl-CoA.

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

    Carnitine palmitoyltransferase I deficiency mainly affects liver function.

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

    Carnitine has an important role in transporting fatty acids into skeletal muscle.

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

    Carnitine deficiency is often associated with impaired muscle function.

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

    The oxidation of branched-chain fatty acids occurs in peroxisomes.

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

    The oxidation of branched-chain fatty acids is different from beta-oxidation because they have a methyl group at position alpha (α) to carboxylic acid.

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

    Peroxisomal oxidation is a more efficient process compared to mitochondrial oxidation.

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

    The omega (ω) oxidation pathway is a less common pathway for fatty acid oxidation and occurs in the endoplasmic reticulum (ER).

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

    Refsum's disease is caused by a deficiency in phytanic acid oxidase.

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

    Beta (β) oxidation is the main catabolic pathway for fatty acids.

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

    Propionyl CoA is formed during the metabolism of odd-chain fatty acids and is further converted to succinyl-CoA for entry into the citric acid cycle.

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

    Ketone bodies are the main energy source for the brain during starvation.

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

    Ketone bodies are produced in the mitochondrial matrix of the liver.

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

    Ketone bodies are a major energy source for the heart and muscle during starvation.

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

    The main purpose of ketone body synthesis is to preserve muscle protein.

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

    Cholesterol biosynthesis is primarily regulated through the feedback inhibition of HMG-CoA reductase.

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

    Statin drugs are highly effective in inhibiting cholesterol biosynthesis.

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

    Cholesterol is essential in synthesis of steroid hormones, bile acids and vitamin D.

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

    Cholesterol is synthesized primarily from the diet rather than from the body.

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

    The rate-limiting step in cholesterol biosynthesis is the conversion of HMG-CoA to mevalonate.

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

    Squalene is synthesized from mevalonate in the cytoplasm.

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

    Lanosterol is converted to cholesterol in 19 steps with the help of oxygen (O2).

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

    Cholesterol biosynthesis is an essential process for cell membrane structure.

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

    The enzyme responsible for catalyzing the formation of bile acids is 7-α-hydroxylase.

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

    The primary role of bile acids is to aid in digestion and absorption of fats.

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

    Bile acids are reabsorbed in the ileum.

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

    Study Notes

    Lipid Metabolism

    • Diagrams and pictures used in the presentation are for teaching purposes only.
    • The topic is Lipid Metabolism.

    Lecture Learning Outcomes/Outline

    • Students should be able to identify/describe:
      • Structure and Role of Lipids - Main classes of lipid, fatty acids: nomenclature and structure (revision)
      • Fatty Acid Biosynthesis - Biosynthesis of saturated fatty acids, elongation of fatty acids, unsaturation of fatty acids & essential fatty acids, regulation of fatty acid synthesis
      • Acylglycerol Metabolism and Mobilization of Lipids - Biosynthesis and hydrolysis of triacylglycerol, glycerophospholipids: biosynthesis and hydrolysis, acylglycerols as energy source for the body, mobilization of adipose tissue lipids
      • Fatty Acid Oxidation and Ketone Bodies - Outline of fatty acid oxidation (β-oxidation) including stoichiometry & regulation, odd carbon fatty acid and unsaturated fatty acid oxidation, regulation of beta oxidation, ketone bodies: synthesis and utilization
      • Cholesterol biosynthesis - overview of cholesterol biosynthesis, bile and steroid synthesis

    Lipids

    • Generally all lipids are associated, either or actually, to fatty acids.
    • Soluble in non-polar solvents and insoluble in polar solvents.
    • Lipids are not polymers.

    Classification of Lipids

    • Simple Lipids:
      • Neutral fats (triacylglycerols)
      • Waxes
      • Cholesterol esters
    • Compound Lipids:
      • Phospholipids
      • Glycolipids
      • Sulpholipids
      • Lipoproteins
      • Aminolipids (proteolipids)
    • Derived Lipids:
      • Fatty acids
      • Monoacylglycerol
      • Diacylglycerol
      • Glycerol
      • Cholesterol
      • Steroids (Vitamins A, D, E, K)
      • Aliphatic Hydrocarbons
      • Carotenoids
      • Squalene
      • Vitamins E and K

    Fatty Acids

    • Saturated fatty acid example: Octanoic Acid
    • Unsaturated fatty acid example: 3-Octenoic Acid, 3,6-Octadienoic Acid, and short-hand notations.
    • Cis and trans fatty acids - examples of Cis 9-Octadecenoic acid (oleic), Trans 9 - Octadecenoic Acid (elaidic acid)
    • Types of fatty acids (according to the number of double bonds): Saturated, Monounsaturated, Polyunsaturated.
    • Naturally occurring fatty acids - examples: Cis form, Not conjugated, Even numbered, Linoleic Acid 18:2 Δ9, Δ12, Linolenic Acid 18:3 Δ9, Δ12, Δ15.

    Fatty Acid Composition of Fats of Animal and Plant Origin

    • Data showing the composition of saturated, monounsaturated, and polyunsaturated fatty acids in various animal and plant fats.

    Melting Points and Solubility in Water of Fatty Acids

    • Melting point increases with increasing chain length
    • Solubility in water decreases with increasing chain length
    • Melting point of fatty acids decreases with increasing number of double bonds

    Effects of Double Bonds on the Melting Points

    • The melting point decreases with increasing number of double bonds.

    Fat and Oils

    • Information on glycerol, fatty acids, and triglycerides.

    Fat from Diet & Adipose Cells

    • Triglycerides are the major form of stored energy in the body.
    • Insulin mediates/stimulates storage of fatty acids in the form of triglycerides.
    • Hormones (glucagon, epinephrine, ACTH) trigger release of fatty acids from adipose tissue.

    Fatty Acid Metabolism

    • Diagram illustrating fatty acid metabolism, including lipogenesis, lipolysis, β-oxidation, ketogenesis, and the TCA/Krebs cycle.
    • Synthesis of fatty acids occurs in the cytosol.

    Source of Acetyl CoA for Fatty Acid Synthesis

    • Glucose → pyruvate → Acetyl CoA
    • Important reactions: Acetyl-CoA carboxylase, Fatty acid synthase

    Acetyl-CoA Carboxylase

    • Irreversible two-step reaction
    • Animal cells - one multifunctional polypeptide
    • Biotin carboxylase
    • Biotin carrier protein
    • Transcarboxylase
    • Requires a biotin prosthetic group

    Fatty Acid Synthesis Requires NADPH

    • Information on how Fatty acid synthesis requires NADPH.

    Initiation of Fatty Acid Synthesis

    • Acetyl CoA is first added to ACP, then transferred to β-Ketoacyl-ACP synthase (KS).
    • Similar process as for the growing fatty acid chain after completion of each cycle.
    • Then Malonyl-CoA is added to ACP.

    Elongation Cycle of Fatty Acid Biosynthesis

    • Malonyl-ACP condensation
    • β-reduction
    • Dehydration
    • Enoyl reduction

    The Total Reaction

    • First Round: 4 carbons long (butyryl)
    • Second Round: 6 carbons long
    • Third Round: 8 carbons long etc....
    • Total of seven rounds to make the product, which is recognized and released by palmitate thioesterase.

    Regulation of Fatty Acid Synthesis

    • Allosteric regulation (Citrate, Acetyl-CoA, Long chain FAs, inhibits carnitine acyltransferase I).
    • Hormonal regulation of Acetyl CoA Carboxylase (Insulin, Glucagon).

    Biosynthesis of TAGs and Phospholipids

    • Two pathways for glycerol-3-phosphate
    • Overview of the steps for TAG biosynthesis
    • Pathways branch to TAG or phospholipids
    • Regulation of TAG Biosynthesis (Insulin and glucagon).

    Biosynthesis of Glycerophospholipids

    • Diagram of Glycerophospholipid synthesis.
    • Includes various enzymes and intermediates in the process.

    Phospholipid Hydrolysis

    • Phospholipase A₁, A₂, C, and D.

    Lipid-based Hormone Biosynthesis

    • Involvement of phospholipids in hormone synthesis.

    Triacylglycerol Hydrolysis

    • Overview of the steps in triacylglycerol hydrolysis (TG + 3H₂O → Glycerol + 3 Fatty Acid + 3H⁺).
    • Involves enzyme lipase.
    • Glycerol and fatty acids are used in other processes.

    The Utilization of Fatty Acids as Fuel

    • The lipids are mobilized from the fat depots (adipose).
    • Triglycerides are degraded to fatty acids and glycerols, then transported to energy requiring tissues.
    • At these tissues, fatty acids must be activated and transported into mitochondria
    • Fatty acids are broken down into Acetyl CoA.

    Oxidation of Fatty Acids

    • α-oxidation - oxidation of branched fatty acids.
    • β-oxidation - Common oxidation.
    • w-oxidation - Alternate pathway.

    Peroxisomal β-Oxidation

    • Peroxisomes - organelles that carry out flavin-dependent oxidations.
    • Electrons go to O₂ rather than e- transport chain.

    Odd-carbon Fatty Acid Oxidation

    • Odd-carbon fatty acids are metabolized normally, until the propionyl-CoA fragment.
    • Three reactions convert propionyl-CoA to succinyl-CoA.
    • Succinyl-CoA cannot directly enter Krebs cycle and is converted to malate then pyruvate and finally acetyl-CoA.

    CoA Activates Fatty Acids for Oxidation

    • Acyl-CoA synthetase condenses fatty acids with CoA, with simultaneous hydrolysis of ATP to AMP and PP₁.
    • Formation of a CoA ester is expensive energetically.
    • Reaction just barely breaks even with ATP hydrolysis.
    • Subsequent hydrolysis of PP drives the reaction strongly forward.
    • Activated fatty acyl CoA is transported into the mitochondria.

    B-Oxidation

    • Overall reaction for the B-oxidation of palmitate.
    • Stoichiometry of palmitate oxidation.

    Regulation of Fatty Acid Oxidation

    • Oxidation of fatty acids occurs when energy levels are low.
    • Enzymes of β-oxidation are regulated by Malonyl-CoA, carnitine acyltransferase I, (regulated by NADH, and acetyl-CoA thiolase).

    Impaired Fatty Acid Oxidation

    • Symptoms - carnitine palmitoyltransferase I & II deficiencies and diseases (preterm infants with inadequate biosynthesis or renal leakage, losses during haemodialysis), leading to increased plasma free fatty acids, lipid accumulation in muscles, muscle weakness, ketoacidosis, sudden infant death syndrome (SIDS), imbalance in glucose and fatty acid oxydation.

    Ketone Bodies

    • Ketone bodies (acetone, acetoacetate, and β-hydroxybutyrate) are synthesized in the liver.
    • Major energy source for brain during starvation.
    • Source of fuel for brain, heart, and muscle.
    • Synthesis pathway - several steps starting from Acetyl-CoA
    • Importance and utilization of acetoacetate
    • Relation to diabetes

    Cholesterol Biosynthesis

    • Steps in cholesterol synthesis
    • Key enzymes (HMG-CoA synthase; HMG-CoA reductase)
    • Feedback regulation of HMG-CoA reductase.
    • Cholesterol's roles in bile acid syntheses and steroid synthesis
    • The amount produced rather from diet itself
    • Cholesterol's roles in bile acid synthesizes.
    • Biosynthesis, rather than diet, contributes the majority of body cholesterol, which can deposit in artery walls.
    • Statin drugs can be used to curtail synthesis, whereas intake of unsaturated fatty acids improves cholesterol clearance.
    • Note: Cholesterol is only excreted from the body in the form of bile.

    Bile Acid Synthesis

    • Cholesterol → Bile Acids (Several steps).

    Steroid Hormone Synthesis in Adrenal Cortex

    • Cholesterol is a precursor to steroid hormones and the steps involved in their synthesis in the Adrenal cortex.

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