Electron Transport Chain and Oxidative Phosphorylation
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Electron Transport Chain and Oxidative Phosphorylation

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Questions and Answers

Which complex of the electron transport chain is responsible for transferring electrons from NADH to coenzyme Q (UQ)?

  • Complex 1 (correct)
  • Complex 3
  • Complex 4
  • Complex 2
  • What is a key difference in the electron transfer process between Complex 1 and Complex 2?

  • Complex 1 pumps 4 H+ out, while Complex 2 does not pump protons. (correct)
  • Complex 1 transfers electrons from FADH2, while Complex 2 transfers from NADH.
  • Complex 2 transfers electrons from NADH, while Complex 1 transfers from FADH2.
  • Complex 1 does not pump protons, while Complex 2 does.
  • What does Complex 3 transfer electrons from and to during its function?

  • From water to NADH
  • From FADH2 to complex 4
  • From NADH to oxygen
  • From reduced UQ (UQH2) to cytochrome c (Cyt c) (correct)
  • Which complex does NOT pump protons into the intermembrane space during electron transfer?

    <p>Complex 2</p> Signup and view all the answers

    What is the end product of the electron transfer process catalyzed by Complex 4?

    <p>H2O</p> Signup and view all the answers

    What is the primary function of reactive oxygen species (ROS) generated during the respiratory burst?

    <p>To destroy pathogens</p> Signup and view all the answers

    Which enzyme is responsible for converting superoxide radicals into hydrogen peroxide and oxygen?

    <p>Superoxide Dismutase</p> Signup and view all the answers

    Which antioxidant is primarily involved in degrading hydrogen peroxide into water and oxygen?

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

    What is the role of glutathione peroxidase in the glutathione-centered antioxidant system?

    <p>To reduce hydrogen peroxide and organic peroxides</p> Signup and view all the answers

    Which radical is NOT produced during the reaction of O2- with nearby molecules in pathogen destruction?

    <p>Methane radical (CH4)</p> Signup and view all the answers

    What conformation does the 𝛽1 subunit adopt when both ADP and Pi bind to their respective sites?

    <p>Loose (L)</p> Signup and view all the answers

    Which condition inhibits oxidative phosphorylation in the mitochondrial matrix?

    <p>High levels of ATP</p> Signup and view all the answers

    How does phosphate (H2PO4-) enter the mitochondrial matrix?

    <p>Co-transport with H+ via phosphate translocase</p> Signup and view all the answers

    What process is initiated by the interaction of the 𝛶-shaft with 𝛽1?

    <p>Binding of ADP and Pi</p> Signup and view all the answers

    Which compound is reduced by NADH in the glycerol-phosphate shuttle?

    <p>Dihydroxyacetone phosphate (DHAP)</p> Signup and view all the answers

    What is the primary function of Cyt c in the electron transport chain?

    <p>It acts as a water-soluble electron carrier.</p> Signup and view all the answers

    How many protons are pumped out of the matrix into the intermembrane space during the transfer from Cyt c to O2?

    <p>4</p> Signup and view all the answers

    What role does ATP play in relation to cytochrome oxidase during electron transfer?

    <p>It inhibits electron transfer.</p> Signup and view all the answers

    What is the main purpose of the chemiosmotic coupling theory in relation to ATP synthesis?

    <p>It details how protons generate ATP through ATP synthase.</p> Signup and view all the answers

    What occurs when the inner mitochondrial membrane is disrupted?

    <p>Respiration stops.</p> Signup and view all the answers

    How many protons are required for the synthesis of one molecule of ATP?

    <p>3</p> Signup and view all the answers

    What components make up the F1 unit of ATP synthase?

    <p>3𝛼, 3𝛽, 𝛶, δ, ε</p> Signup and view all the answers

    Which of the following best describes the role of uncouplers like Dinitrophenol?

    <p>They collapse the H+ gradient.</p> Signup and view all the answers

    What does the ‘18’ in the fatty acid notation ‘18:2𝜔-6’ represent?

    <p>The number of carbon atoms</p> Signup and view all the answers

    Which fatty acids are classified as essential fatty acids?

    <p>Linoleic acid and 𝛼-linolenic acid</p> Signup and view all the answers

    What is the primary source of 𝜔-3 fatty acids?

    <p>Fish and fish oils</p> Signup and view all the answers

    Which type of fatty acids promotes inflammation?

    <p>𝜔-6 derived eicosanoids</p> Signup and view all the answers

    How are triacylglycerols characterized?

    <p>Esters of glycerol with three fatty acids</p> Signup and view all the answers

    What process involves the hydrolysis of triacylglycerols to produce soap?

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

    Which phospholipid is known as lecithin?

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

    What role do phospholipids play in biological systems?

    <p>Constitute cell membranes</p> Signup and view all the answers

    What describes the structure of waxes?

    <p>Complex mixtures of nonpolar lipids</p> Signup and view all the answers

    What is the healthy ratio of 𝜔-6 to 𝜔-3 fatty acids believed to influence inflammation?

    <p>1:1 to 1:4</p> Signup and view all the answers

    Which fatty acid is a precursor for arachidonic acid?

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

    What kind of emulsifying agent do soaps act as in water?

    <p>Amphipathic agents</p> Signup and view all the answers

    Which of the following is a characteristic of saturated fatty acids?

    <p>Solid at room temperature</p> Signup and view all the answers

    Which compound is found in the inner leaflet of membranes and also known as cephalin?

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

    What is the primary role of cardiolipin in the mitochondrial inner membrane?

    <p>Stabilizing the electron transport chain</p> Signup and view all the answers

    Which signaling molecules are derived from phosphatidylinositol-4,5-bisphosphate (PIP2)?

    <p>Diacylglycerol (DAG) and inositol triphosphate (IP3)</p> Signup and view all the answers

    Which statement accurately describes the function of phospholipases?

    <p>They hydrolyze ester bonds in glycerophospholipids</p> Signup and view all the answers

    Which of the following is true regarding phosphatidylethanolamine?

    <p>It plays a significant role in membrane fusion and flexibility.</p> Signup and view all the answers

    Which type of phospholipase hydrolyzes the bond at C1 of the glycerol backbone?

    <p>PLA1</p> Signup and view all the answers

    What role does cardiolipin play in mitochondria?

    <p>Facilitates the electron transport chain and ATP production</p> Signup and view all the answers

    Which of the following statements accurately describes phospholipase enzymatic actions?

    <p>They hydrolyze phospholipids to release fatty acids</p> Signup and view all the answers

    Which type of sphingolipid contains a monosaccharide as its head group?

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

    How do signaling molecules derived from phosphatidylinositol function in cellular processes?

    <p>They facilitate intracellular calcium signaling and activate protein kinases</p> Signup and view all the answers

    Which characteristic is unique to sulfatides among glyolipids?

    <p>They have a negatively charged head group at physiological pH</p> Signup and view all the answers

    What is a primary function of phosphatidylethanolamine in biological membranes?

    <p>Facilitating membrane curvature and fusion</p> Signup and view all the answers

    What role does cardiolipin play in mitochondria?

    <p>It provides structural stability to mitochondrial membranes</p> Signup and view all the answers

    Which of the following signaling molecules can be derived from phosphatidylinositol?

    <p>Inositol trisphosphate</p> Signup and view all the answers

    What is the primary action of phospholipase enzymes?

    <p>To hydrolyze phospholipids</p> Signup and view all the answers

    Which type of sphingolipid is involved in nerve signal transmission?

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

    What is the composition of phosphatidylethanolamine?

    <p>Glycerol, two fatty acids, phosphate, and an ethanolamine</p> Signup and view all the answers

    Which sphingolipid is known for being a component in the cell membranes of neurons?

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

    Which of the following is NOT a function of eicosanoids derived from omega-3 fatty acids?

    <p>Promoting inflammation</p> Signup and view all the answers

    What characterizes the structure of sphingolipids?

    <p>A long-chain fatty acid, a phosphate group, and a sphingosine backbone</p> Signup and view all the answers

    Which enzyme is involved in the dephosphorylation of phosphatidylinositol?

    <p>Phospholipase C</p> Signup and view all the answers

    Which property do phospholipids possess that makes them essential for cell membrane structures?

    <p>They are amphiathic in nature</p> Signup and view all the answers

    What type of eicosanoids are derived from arachidonic acid?

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

    Which type of lipid modification occurs in sphingolipids to enhance their function?

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

    What is a key feature of phosphatidylglycerol within biological systems?

    <p>It acts as a lung surfactant and indicator for fetal lung maturity</p> Signup and view all the answers

    What compound is formed when sphinganine reacts with a long chain fatty acid?

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

    What is the role of sphingomyelin in the nervous system?

    <p>Insulates nerves and facilitates rapid transmission of nerve impulses</p> Signup and view all the answers

    Which compound is involved in the degradation of sphingomyelin?

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

    What type of sugar head group is present in cerebrosides?

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

    What occurs due to a defective sphingomyelinase?

    <p>Accumulation of sphingomyelin leading to Niemann-Pick Syndrome</p> Signup and view all the answers

    What is the primary consequence of macrophages accumulating LDL in the presence of high levels?

    <p>They become foam cells.</p> Signup and view all the answers

    What critical molecule's synthesis may be affected by statin therapy?

    <p>Ubiquinone (UQ)</p> Signup and view all the answers

    Which organ plays a key role in regulating blood glucose levels?

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

    Which hormone stimulates appetite and is secreted by the stomach?

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

    What is the effect of the hormone peptide YY (PYY) secreted by the small intestine?

    <p>Inhibits appetite</p> Signup and view all the answers

    Which mechanism is primarily responsible for the hardening and narrowing of heart arteries due to plaque buildup?

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

    What type of drugs lower blood cholesterol by inhibiting HMG-CoA reductase?

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

    What can happen as foam cells necrose in the plaques within blood vessels?

    <p>Cholesterol crystals form</p> Signup and view all the answers

    What is the primary role of adipose tissue in the body?

    <p>Stores energy in the form of triglycerides</p> Signup and view all the answers

    Which hormone is secreted by adipose tissue to promote satiety?

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

    During prolonged fasting, which substances primarily provide energy for muscles?

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

    What triggers insulin release from pancreatic β-cells after a meal?

    <p>Glucose movement from the intestine to the liver</p> Signup and view all the answers

    What is the main function of glucagon during fasting?

    <p>Stimulates gluconeogenesis and glycogenolysis</p> Signup and view all the answers

    How does the brain contribute to metabolic processes?

    <p>Directs most metabolic activities</p> Signup and view all the answers

    What is the main effect of insulin on skeletal muscle?

    <p>Activates glucose uptake through GLUT4 translocation</p> Signup and view all the answers

    What efficiently maintains stable internal environments in the body?

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

    What is a consequence of defective 𝛽-glucosidase enzyme activity?

    <p>Gaucher’s disease</p> Signup and view all the answers

    Which enzyme is responsible for degrading galactocerebrosides?

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

    Which of the following is a result of cholesterol accumulation in the body?

    <p>Inhibition of LDL receptor synthesis</p> Signup and view all the answers

    What is the primary site of cholesterol synthesis in the body?

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

    What role does Insig play in cholesterol homeostasis?

    <p>Retains SREBP2 in the endoplasmic reticulum</p> Signup and view all the answers

    What is the consequence of low cellular cholesterol levels on HMGR activity?

    <p>Stimulation of HMGR activity</p> Signup and view all the answers

    Which of the following phases is NOT involved in cholesterol synthesis?

    <p>Conversion of squalene to bile acids</p> Signup and view all the answers

    What regulates the expression of the HMGR gene in response to cholesterol levels?

    <p>SREBP2</p> Signup and view all the answers

    What happens to SREBP2 when cholesterol levels are low?

    <p>It is released from the ER to Golgi complex</p> Signup and view all the answers

    Which enzyme's activity is inhibited by glucagon and epinephrine via phosphorylation?

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

    What occurs to the brain's energy source after several weeks of fasting?

    <p>It adapts to use ketone bodies as an energy source.</p> Signup and view all the answers

    Which hormone is responsible for stimulating food intake?

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

    What is a primary difference between Type 1 and Type 2 diabetes?

    <p>Type 1 results from autoimmune destruction of insulin-producing cells, Type 2 is caused by insulin resistance.</p> Signup and view all the answers

    What effect does leptin have on appetite regulation?

    <p>It inhibits appetite.</p> Signup and view all the answers

    What is the major symptom related to high blood glucose in diabetes?

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

    What is the role of the arcuate nucleus (ARC) in the hypothalamus?

    <p>It controls appetite through neural circuits.</p> Signup and view all the answers

    During prolonged fasting, what does the body primarily utilize for gluconeogenesis?

    <p>Amino acids from muscle protein.</p> Signup and view all the answers

    What triggers frequent urination (polyuria) in diabetes?

    <p>Presence of glucose in the urine.</p> Signup and view all the answers

    Which treatment option is primarily used for Type 1 diabetes?

    <p>Insulin injection or infusion.</p> Signup and view all the answers

    Why are humans increasingly predisposed to obesity in the modern world?

    <p>Increased availability of unhealthy food options.</p> Signup and view all the answers

    Study Notes

    Electron Transport Chain

    • Four complexes are embedded in the inner mitochondrial membrane, facilitating electron transfer: Complex 1, Complex 2, Complex 3, and Complex 4.
    • Complex 1 (NADH Dehydrogenase Complex) transfers electrons from NADH to coenzyme Q (UQ), pumping four protons (H+) from the matrix into the intermembrane space.
    • Complex 2 (Succinate Dehydrogenase Complex) transfers electrons from FADH2 to UQ, but doesn't pump protons across the membrane.
    • Complex 3 (Cytochrome bc1 Complex) transfers electrons from reduced UQ (UQH2) to cytochrome c (Cyt c), pumping four protons from the matrix into the intermembrane space.
    • Complex 4 (Cytochrome Reductase) transfers four electrons from four Cyt c to oxygen (O2), forming water (H2O), and pumping another four protons from the matrix into the intermembrane space.

    Oxidative Phosphorylation

    • Oxidative phosphorylation utilizes the energy released from the electron transport chain for the synthesis of ATP from ADP.
    • The electron transport chain pumps protons from the matrix into the intermembrane space, creating a proton motive force.
    • The Chemiosmotic Coupling Theory explains how this proton motive force drives ATP formation.

    Chemiosmotic Theory

    • The movement of protons from the intermembrane space back into the matrix via ATP synthase drives ATP production.
    • Evidence for the Chemiosmotic Theory includes:
      • A decrease in pH within weakly buffered mitochondria during active respiration.
      • Disruption of the inner mitochondrial membrane stops respiration.
      • Uncouplers (like Dinitrophenol) collapse the proton gradient by carrying protons across the membrane.
      • Ionophores (like Gramicidin A) create channels, allowing protons to pass through and disrupt the proton gradient.

    ATP Synthase

    • ATP synthase consists of two components: the F1 unit (ATP synthase) and the F0 unit (transmembrane channel).
    • The F1 unit:
      • Composed of five subunits: 3α, 3β, γ, δ, and ε.
      • Subunits α and β form the catalytic core.
    • The F0 unit:
      • Composed of three subunits: a, 2b, and 12c.
      • Creates a channel through the membrane for proton movement.
    • The F0 unit converts the proton motive force into rotational force within the central shaft (γ and ε subunits), which powers the ATP synthase.
    • The formation of one ATP molecule requires the movement of three protons through ATP synthase.

    𝛽-Subunits

    • The three β subunits of ATP synthase undergo conformational changes:
      • Loose (L) conformation: ADP and Pi bind.
      • Tight (T) conformation: ADP and Pi join to form ATP.
      • Open (O) conformation: ATP is released into the matrix.
    • The γ subunit interacts with the β subunits, triggering these conformational changes.

    Transport Across the Mitochondrial Membrane

    • ATP is synthesized in the mitochondrial matrix and exits through the ADP-ATP translocator.
    • ADP enters the matrix through the same translocator.
    • Inorganic phosphate (Pi) is transported into the matrix as H2PO4- via the phosphate translocase, which also transports a proton.

    Regulation of Oxidative Phosphorylation

    • High levels of ADP and Pi in the matrix activate oxidative phosphorylation.
    • High levels of ATP in the matrix inhibit oxidative phosphorylation.
    • The ADP-ATP translocator regulates mitochondrial ATP and ADP levels.
    • The phosphate translocase regulates the H2PO4- concentration in the matrix.

    Glycerol-Phosphate Shuttle

    • The Glycerol-Phosphate Shuttle transports cytoplasmic NADH into the mitochondrial matrix.
    • Cytoplasmic NADH reduces dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate.
    • Glycerol-3-phosphate diffuses across the outer mitochondrial membrane and reduces FAD to FADH2.
    • FADH2 enters the electron transport chain at Complex 2, contributing to ATP synthesis.

    Respiratory Burst

    • Macrophages and neutrophils produce large amounts of reactive oxygen species (ROS) to destroy pathogens.
    • During phagocytosis, NADPH oxidase on phagolysosome membranes converts oxygen (O2) into superoxide (O2-), a reactive oxygen species.
    • Superoxide reacts with other molecules to generate hydroxyl radical (OH), hypochlorite (OCl-), peroxynitrite (ONOO-), and nitrogen dioxide (NO2) radicals.
    • These reactive species are toxic to pathogens, contributing to their destruction.

    Antioxidants

    • Living organisms have developed defense mechanisms against oxidative stress:
      • Enzyme Systems:
        • Superoxide Dismutase (SOD): Converts superoxide to hydrogen peroxide (H2O2) and oxygen (O2).
        • Catalase: Degrades hydrogen peroxide to water (H2O) and oxygen (O2).
        • Glutathione-centered System: Uses glutathione (GSH) to reduce hydrogen peroxide and organic hydroperoxides, protecting against oxidative damage.
        • Thioredoxin-centered System: Functions similarly to the glutathione system for reducing hydrogen peroxide, reducing oxidative stress.
      • Molecule Systems:
        • Alpha-tocopherol (Vitamin E): Protects against lipid peroxidation.
        • Beta-carotene (Vitamin A): Acts as an antioxidant, minimizing free radical damage.
        • Ascorbic Acid (Vitamin C): An important antioxidant, scavenging free radicals and promoting immune function.

    Fatty Acid Nomenclature

    • The ω Numbering System is used to describe fatty acid structure:
      • The number before the colon indicates the number of carbon atoms in the molecule.
      • The number after the colon indicates the number of double bonds.
      • The number following the ω indicates the position of the first double bond, counting from the ω- end (methyl terminus) of the fatty acid chain.

    Essential and Nonessential Fatty Acids

    • Plants and bacteria synthesize all required fatty acids, but animals acquire most from dietary sources.
    • Nonessential fatty acids can be synthesized by animals.
    • Essential fatty acids cannot be synthesized by animals and must be obtained from the diet:
      • Linoleic acid (omega-6 fatty acid): Precursor for many derivatives including arachidonic acid.
      • Alpha-linolenic acid (omega-3 fatty acid): Precursor for EPA and DHA.

    Omega-6 Fatty Acids

    • Linoleic acid (18:2ω-6) is a key precursor for:
      • Gamma-linolenic acid (18:3ω-6)
      • Arachidonic acid (20:4ω-6)
      • Docosapentaenoic acid (22:5ω-6)
    • Food sources include: Vegetable oils (sunflower, soybean), eggs, poultry.

    Omega-3 Fatty Acids

    • Alpha-linolenic acid (18:3ω-3) is a precursor for:
      • Eicosapentaenoic Acid (EPA) (20:5ω-3)
      • Docosahexaenoic Acid (DHA) (22:6ω-3)
    • Sources include:
      • Flaxseeds, soybean oils, walnuts
      • EPA and DHA are found in fish (salmon, tuna, sardines) and fish oils.
    • Health benefits of omega-3 fatty acids:
      • Promote cardiovascular health.
      • Lower blood triacylglycerol levels.
      • Lower blood pressure.
      • Decrease platelet aggregation.

    Eicosanoids

    • Eicosanoids are hormone-like molecules derived from omega-6 and omega-3 fatty acids.
    • Types include:
      • Prostaglandins
      • Thromboxanes
      • Leukotrienes
    • They regulate:
      • Smooth muscle contraction
      • Blood flow
      • Inflammation
      • Pain perception
    • Omega-6 derived eicosanoids promote inflammation.
    • Omega-3 derived eicosanoids have anti-inflammatory properties.
    • The ratio of omega-6 to omega-3 fatty acids in the diet influences the production of inflammatory and anti-inflammatory eicosanoids.

    Triacylglycerols

    • Triacylglycerols (Triglycerides) are esters of glycerol with three fatty acids.
    • They are neutral fats, meaning they have no charge.
    • They contain fatty acids of varying lengths and have a mixture of saturated and unsaturated fatty acids.
    • Monoacylglycerols and diacylglycerols are intermediates in triacylglycerol metabolism.

    Properties of Triacylglycerols

    • Triacylglycerols can be fats or oils based on their fatty acid composition:
      • Fats are solid at room temperature and have a high proportion of saturated fatty acids.
      • Oils are liquid at room temperature and have a high proportion of unsaturated fatty acids.
    • Saponification is a process that produces soap:
      • Heating oil with KOH or NaOH hydrolyzes triacylglycerols to glycerol and potassium or sodium salts of fatty acids (soap).
      • The soap forms micelles in water due to its amphipathic nature.
      • Soap acts as an emulsifying agent, dispersing grease and oil droplets in micelles.

    Wax Esters

    • Waxes are complex mixtures of nonpolar lipids that are essential for protective coatings in plants and animals.
    • Waxes contain long-chain fatty acids esterified with long-chain alcohols.

    Phospholipids

    • Phospholipids are amphipathic molecules with a polar head group (phosphate and charged groups) and hydrophobic fatty acid tails.
    • Phospholipids play a vital role in cell membranes, forming ordered structures like monolayers, micelles, and bilayer vesicles.

    Types of Phospholipids

    • Phospholipids are classified into two categories:
      • Phosphoglycerides: Contain glycerol, two fatty acids, a phosphate, and an alcohol.
      • Sphingolipids: Contain a sphingosine backbone, a fatty acid, and a phosphate group linked to variable head group.

    Phosphoglycerides

    • The simplest phosphoglyceride is phosphatidic acid, which contains glycerol-3-phosphate and two fatty acids.
    • Phosphatidylcholine (PC) (Lecithin) is a major component of biological membranes, functioning as a surfactant.
    • Phosphatidylserine (PS) is a key component of biological membranes and acts as a signal for macrophages to engulf cells.
    • Phosphatidylglycerol is present in the lungs and amniotic fluid, playing a crucial role as a surfactant and indicating fetal lung maturity.

    Phosphatidylethanolamine and Diphosphatidylglycerol

    • Both Phosphatidylethanolamine and Diphosphatidylglycerol have relatively smaller polar head groups and are often found in the inner leaflet of cellular membranes.
    • Phosphatidylethanolamine is also called cephalin.

    Lipid Classification

    • Lipids are a diverse group of naturally occurring molecules that are soluble in organic solvents.
    • They are a major component of cell membranes and serve as energy storage.
    • Lipid classification is based on their structure and function.
      • Fatty Acids: Amphipathic molecules with a long hydrocarbon chain
        • The length of the hydrocarbon chain varies.
        • Saturated fatty acids have no double bonds between carbon atoms.
        • Unsaturated fatty acids have one or more double bonds.
        • The location of double bonds in unsaturated fatty acids is important for their biological activity.
          • 𝜔 Number System: Used to describe the position of the first double bond starting from the methyl end of the fatty acid.
            • Example: Linoleic acid (18:2𝜔-6) is an 𝜔-6 fatty acid.
              • 18 indicates the number of carbons in the fatty acid.
              • 2 indicates the number of double bonds.
              • 𝜔-6 indicates the position of the first double bond from the 𝜔 carbon.
        • Fatty acids are important for structure and function within membranes.
      • Triacylglycerols (Triglycerides): Ester of glycerol with three fatty acids.
        • Neutral fats, with no charge.
        • Contain varying length fatty acids with a mixture of saturated and unsaturated fatty acids.
        • Solid (fats) at room temperature (high saturated fatty acid content)
        • Liquid (oils) at room temperature (high unsaturated fatty acid content)
        • Saponification: The process that produces soap.
          • Hydrolyzes triacylglycerol to glycerol and salts of fatty acids.
          • Soap forms micelles in water, acting as an emulsifying agent to help disperse fat droplets.
      • Waxes: Complex, nonpolar mixtures of long-chain fatty acids and long-chain alcohols.
        • Found as protective coatings on plants and animals.
      • Phospholipids: Amphipathic molecules with a polar head group (phosphate and charged groups) and nonpolar fatty acid tails.
        • Essential for cell membranes, forming lipid monolayers, micelles, and bilayer vesicles.
        • Two main types:
          • Phosphoglycerides: contain glycerol, two fatty acids, a phosphate, and an alcohol.
            • Important phosphoglycerides:
              • Phosphatidylcholine (Lecithin): Major component of biological membranes, a surfactant.
              • Phosphatidylserine (PS): Important for biological membranes, signaling for macrophages to engulf cells.
              • Phosphatidylglycerol: Present in the lungs and amniotic fluid, functions as a surfactant.
              • Phosphatidylethanolamine (Cephalin): Found in the inner leaflet of membranes, stabilizing membrane curvature.
              • Diphosphatidylglycerol (Cardiolipin): Found in the mitochondrial inner membrane, helping to stabilize the electron transport chain.
            • Phospholipases: Hydrolyse the ester bonds in phosphoglycerides. - PLA1: Hydrolyzes the ester bond at C1 of glycerol. - PLA2: Hydrolyzes the ester bond at C2 of glycerol. - PLB: Hydrolyzes both C1 and C2 ester bonds. - PLC: Hydrolyzes the phosphodiester bond between glycerol and phosphate. - PLD: Hydrolyzes the phosphodiester bond between phosphate and fatty acid (i.e. R3).
            • Acyltransferases: Add fatty acids to phosphoglycerides.
          • Sphingolipids: Contain sphingosine, a fatty acid, and a head group.
            • Ceramide: Fatty acid amide derivative of sphingosine, the core for sphingomyelin and glycolipids.
            • Sphingomyelin: Involved in nerve cell insulation and rapid nerve impulse transmission.
            • Glycolipids: Contain an oligosaccharide attached to ceramide. - Found on the extracellular side of eukaryotic membranes. - Functions: Maintain membrane stability, facilitate cell-cell interactions, and act as receptors for viruses and pathogens. - Important classes of glycolipids: - Cerebrosides - Sulfatides - Gangliosides
      • Isoprenoids: Contain repeating isoprene units.
        • Terpenes: Two isoprene units joining to form monoterpenes (used in perfumes).
        • Tetraterpenes (Carotenoids): Four isoprene units joined together, pigments.
        • Steroids: Derivatives of triterpenes with four fused rings (e.g., cholesterol).

    Essential Fatty Acids

    • Essential fatty acids (EFAs) are fatty acids that cannot be synthesized by the body and need to be obtained from the diet.
    • Omega-6 Fatty Acids:
      • Linoleic Acid (18:2𝜔-6): Precursor to numerous derivatives, including:
        • 𝛶-linolenic acid (18:3𝜔-6)
        • Arachidonic acid (20:4𝜔-6)
        • Docosapentanenoic (22:5𝜔-6) (DPA)
      • Food sources: Vegetable oils (sunflower and soybean), eggs, poultry
    • Omega-3 Fatty Acids:
      • 𝛼-linolenic acid (18:3𝜔-3): Precursor to:
        • Eicosapentaenoic Acid (20:5𝜔-3) (EPA)
        • Docosahexaenoic Acid (22:6𝜔-3) (DHA)
      • Sources: Flaxseeds, soybean oil, walnuts, fish (salmon, tuna, sardines), and fish oils.
      • Health Benefits: Enhance cardiovascular health, lower blood triacylglycerol levels, reduce blood pressure, and decrease platelet aggregation.
    • Eicosanoids: Hormone-like molecules derived from 𝜔-6 and 𝜔-3 fatty acids.
      • Prostaglandins, Thromboxanes, and Leukotrienes: Influence smooth muscle contraction, blood regulation, inflammation, and pain perception.
        • 𝜔-6 derived eicosanoids promote inflammation.
        • 𝜔-3 derived eicosanoids have an anti-inflammatory effect.

    Sphingolipid Synthesis

    • Sphingosine is synthesized from palmitoyl-CoA and serine to form sphinganine.
    • Ceramide is formed when sphinganine reacts with a long-chain fatty acid.
    • Sphingomyelin is synthesized from ceramide and either phosphatidylcholine or phosphatidylethanolamine.
    • Galactocerebroside is formed when ceramide reacts with UDP-galactose.
    • Glucocerebroside is formed when ceramide reacts with UDP-glucose.

    Sphingomyelin Metabolism

    • Sphingomyelin is a phospholipid that insulates nerves and facilitates rapid nerve impulse transmission.
    • Sphingomyelinase degrades sphingomyelin.
    • Niemann-Pick Syndrome is caused by a deficiency in sphingomyelinase, leading to an accumulation of sphingomyelin.

    Cerebroside Metabolism

    • Cerebrosides are sphingolipids with a monosaccharide head group.
    • Glucocerebroside is found in non-neuronal tissues and is degraded by β-glucosidase.
    • Gaucher's disease is caused by a deficiency in β-glucosidase, leading to an accumulation of glucocerebrosides.
    • Galactocerebroside is found in brain cell membranes and is degraded by β-galactosidase.
    • Krabbe's disease is caused by a deficiency in β-galactosidase, leading to an accumulation of galactocerebrosides.
    • Sulfatides are sulfated galactocerebrosides degraded by Arylsulfatase A.
    • Alzheimer's and Parkinson's diseases can be linked to the accumulation of sulfatide due to a deficiency in Arylsulfatase A.

    Ganglioside Metabolism

    • Gangliosides are sphingolipids containing oligosaccharide groups with one or more sialic acid residues.
    • GM2 gangliosides are degraded by β-Hexosaminidase.
    • Tay-Sachs disease is caused by a deficiency in β-hexosaminidase A, leading to an accumulation of GM2 gangliosides.

    Cholesterol Synthesis

    • Cholesterol is synthesized from isoprenoids and is a precursor for bile salts and steroid hormones.
    • Cholesterol is obtained from the diet and synthesized de novo.
    • Most cholesterol synthesis takes place in the liver.
    • Dietary cholesterol inhibits cholesterol synthesis and LDL receptor synthesis.
    • Insufficient dietary cholesterol intake stimulates LDL receptor and HMG-CoA reductase (HMGR) synthesis.

    Cholesterol Synthesis Phases

    • Phase 1: Acetyl-CoA is converted to HMG-CoA.
    • Phase 2: HMG-CoA is converted to squalene.
    • Phase 3: Squalene is converted to cholesterol.

    Cholesterol Homeostasis

    • Cholesterol is crucial for biological functions, but excessive amounts can be toxic.
    • Blood cholesterol levels are regulated through the intricate control of bile acid synthesis and cholesterol synthesis.
    • HMG-CoA reductase (HMGR) is a key enzyme for regulating cholesterol biosynthesis.

    Regulation of Cholesterol Biosynthesis

    • Covalent modification: phosphorylation/dephosphorylation of HMGR regulates its activity.
      • Glucagon and epinephrine inhibit HMGR activity by activating phosphoprotein phosphatase (PRO).
      • Insulin activates HMGR activity by inhibiting cAMP production.
    • Genomic modification: Steroid regulation of gene expression alters HMGR levels.

    Covalent Regulation of HMGR

    • HMGR activity is regulated by phosphorylation or dephosphorylation.
    • Glucagon and epinephrine inhibit HMGR activity by activating PRO.
    • Insulin activates HMGR activity by inhibiting cAMP production.

    Genomic Regulation of Cholesterol Biosynthesis

    • Sterol-regulatory-element-binding protein-2 (SREBP2) is a membrane protein in the ER that regulates cholesterol homeostasis.
    • SREBP2 regulates LDL receptor expression and NADPH synthesis.
    • When cholesterol levels are low, the transcription factor domain of SREBP2 is released.

    Functional Units of SREBP2

    • SREBP2 has a transcription factor domain (TFD), a sterol-sensing domain (SSD), and a binding site for Insulin-induced gene (Insig).
    • Insig is a retention protein that keeps SREBP2 in the ER.

    Sterol-Mediated Gene Expression

    • High cholesterol levels keep Insig bound to SSD, retaining SREBP2 in the ER.
    • Low cholesterol levels release Insig from SSD.
    • The SREBP/SCAP complex is transferred from the ER to the Golgi complex.
    • Two proteases cleave SREBP2 in the Golgi, releasing the active TFD.
    • TFD moves to the nucleus and binds to sterol regulatory elements (SRE) of sterol-related genes, stimulating mRNA synthesis.

    Sterol Regulation of HMGR Gene Expression

    • Low cellular cholesterol stimulates:
      • Cholesterol biosynthesis (e.g., HMGR) expression.
      • LDL receptor gene expression.
      • NADPH synthesizing genes: glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase, malic enzyme.

    Atherosclerosis

    • Atherosclerosis is the hardening and narrowing of arteries due to plaque buildup.
    • Macrophages have LDL receptors that bind and oxidize LDL.
    • High LDL levels lead to macrophage accumulation of LDL, transforming them into foam cells.
    • Foam cells stick to blood vessel walls and promote plaque formation.
    • As foam cells necrose, cholesterol crystals form in the plaques.
    • Atheromas (plaques) can block blood flow and rupture veins.

    High Cholesterol and Drug Therapy

    • High total cholesterol (VLDL, LDL, and HDL) combined with high LDL is strongly associated with cardiovascular disease.
    • Statins are drugs that lower blood cholesterol by inhibiting HMGR.
    • Statins are usually taken in the evening because most cholesterol synthesis occurs at night.
    • Statin therapy may be accompanied by CoQ supplements because statins can interfere with ubiquinone (UQ) synthesis.

    Organ Sparing Metabolic Workload in Feeding-Fasting Cycle

    • Gastrointestinal (GI) tract: mixes, digests, absorbs, and propels food.
    • Liver: crucial for nutrient metabolism, regulates blood glucose, and detoxifies.
    • Muscle: skeletal and cardiac muscle consume a large portion of energy.
    • Adipose tissue: stores energy as triglycerides.
    • Brain: directs most metabolic processes.
    • Kidney: maintains internal body environments.

    Role of Gastrointestinal Tract

    • The stomach secretes ghrelin, a hormone that stimulates appetite.
    • The small intestine secretes peptide YY (PYY), a hormone that inhibits appetite.
    • Pancreatic β-cells secrete insulin, a hormone that stimulates glucose uptake by muscle.
    • Pancreatic α-cells secrete glucagon, a hormone that stimulates catabolism.

    Role of Liver and Muscle

    • The liver plays a key role in nutrient metabolism, regulating blood glucose levels.
    • Muscle consumes a large portion of the body's energy and uses fatty acids in the fasting state.
    • Insulin activates glucose absorption into skeletal and cardiac muscle through GLUT4 translocation.

    Role of Adipose Tissue, Brain, and Kidney

    • Adipose tissue stores energy as triglycerides and secretes leptin, which promotes satiety (inhibits appetite).
    • The brain directs most metabolic processes, and the hypothalamus plays a critical role in energy balance.
    • The kidney maintains internal body environments.

    Feeding-Fasting Cycle

    • Mammals consume food intermittently due to the mechanism for storing and mobilizing energy.
    • Hormone regulation and substrate concentrations control metabolism.
    • Postprandial state: after a meal, nutrient levels are high.
    • Post-absorptive state: overnight fasting, nutrient levels are low.

    Feeding Phase

    • Nutrients are absorbed from the intestine and transported to the liver.
    • Glucose movement from the intestine to the liver stimulates insulin release from β-cells.
    • Insulin triggers glucose uptake, glycogen synthesis, fat synthesis and storage, and protein synthesis.
    • Lipids are transported as chylomicrons to muscle and adipose tissue.
    • Chylomicron remnants deliver phospholipids, cholesterol, and remaining triglycerides to the liver.

    Fasting Phase

    • Decreased blood glucose and insulin levels induce glucagon release from α-cells.
    • Glucagon stimulates glycogenolysis and gluconeogenesis in the liver, preventing hypoglycemia.
    • Fatty acid mobilization maintains blood glucose during prolonged fasting.
    • Muscles use fatty acids to conserve glucose for the brain and red blood cells.
    • During starvation, fatty acids from adipose tissue and ketone bodies from the liver are mobilized.
    • Gluconeogenesis is essential after 7 hours of fasting, as glycogen is depleted.
    • Amino acids from muscle protein are used for gluconeogenesis.
    • After several weeks of fasting, the brain adapts to using ketone bodies as an energy source.

    Feeding Behavior

    • Feeding behavior is regulated by hormone and neuronal signals, as well as sensory input from the environment.
    • The arcuate nucleus (ARC) in the hypothalamus plays a key role in regulating appetite.
    • The ARC contains two types of neurons:
      • Agouti-related protein (AgRP) and neuropeptide Y (NPY) neurons: stimulate appetite.
      • Pro-opiomelanocortin (POMC) neurons: inhibit appetite.

    Ghrelin and Food Intake

    • Ghrelin, a stomach hormone, stimulates food intake by activating AgRP/NPY neurons.

    Leptin and Food Intake

    • Leptin, insulin, and PYY inhibit AgRP/NPY neurons, reducing food intake.
    • Leptin activates POMC neurons, further inhibiting appetite.

    Diabetes Mellitus

    • Diabetes mellitus is a metabolic disease with two main types: type 1 and type 2.
    • Both types of diabetes are marked by the inability of cells to acquire glucose from the blood, leading to hyperglycemia.

    Type 1 Diabetes

    • Known as juvenile diabetes or insulin-dependent diabetes.
    • An autoimmune disease where the β-cells of the pancreas are destroyed.
    • Characterized by inadequate insulin production.
    • Symptoms include thirst, frequent urination (polyuria), and ketosis.
    • Treatment involves insulin injection or infusion.

    Type 2 Diabetes

    • Known as insulin-independent diabetes.
    • Caused by insulin resistance in target cells.
    • Treatment includes diet, exercise, and sometimes insulin therapy.

    Symptoms of Diabetes

    • Dysfunctional fuel metabolism is a defining feature.
    • Major symptoms include hyperglycemia, glucosuria, and dyslipidemia.
    • Hyperglycemia is high blood glucose, a symptom of both type 1 and type 2 diabetes.
    • Glycosuria is the presence of glucose in urine, causing osmotic diuresis and polyuria, leading to excessive thirst.
    • Dyslipidemia is abnormal blood lipid and lipoprotein levels.

    Obesity

    • The reasons for the predisposition to obesity in the modern world are complex and multifactorial.

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