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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    Explore the intricate processes of the electron transport chain and oxidative phosphorylation in cellular respiration. Understand the roles of the four complexes involved in electron transfer and ATP synthesis. This quiz will test your knowledge of mitochondrial function and energy production.

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