BI110 Lecture 11 - Biology Lecture Notes PDF

BI110 Lecture 11 – Wed. Oct. 23 Dr. Leonard Reminders: SI sessions Sunday, Monday and Wednesday  Reminders TODAY: Review Chapter 4 – Cell Membranes and Signalling and start Chapter 5 Chapter 4 MindTap assignment is due Sunday, Oct 27th at 11:59 PM Midter...

BI110 Lecture 11 – Wed. Oct. 23 Dr. Leonard Reminders: SI sessions Sunday, Monday and Wednesday  Reminders TODAY: Review Chapter 4 – Cell Membranes and Signalling and start Chapter 5 Chapter 4 MindTap assignment is due Sunday, Oct 27th at 11:59 PM Midterm #2: Wed. Nov. 20 during class  Signal Transduction Pathways The binding of a signal molecule to a plasma membrane receptor on the cell surface activates a signalling cascade But the signal molecule does not enter the cell Molecules that are similar to the signal molecule can trigger or block a full cellular response if they can bind to the recognition site of the receptor Many drug treatments target signal transduction pathways; some work at the level of the receptor  Signal Transduction Pathways Signals are often relayed in cell by protein kinases Enzymes that transfer phosphate group from ATP to one or more sites on specific target protein Added phosphate groups stimulate or inhibit activities of target proteins Protein phosphatases Reverse response by removing phosphate groups from target proteins  continuously active Some signalling cascades involve production of second messengers cAMP  Phosphorylation Protein kinases often act in a chain, catalyzing a series of phosphorylation reactions called a phosphorylation cascade to pass along a signal Each kinase catalyzes phosphorylation of another in the cascade—the last protein in the cascade is the target protein Phosphorylation of a target protein stimulates or inhibits its activity (depending on the particular protein), which brings about the cellular response Phosphorylation Cascade [Insert Fig. 4.24 on p. 95] Fig. 4.24  Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active Ph protein o kinase sp 1 ho Inactive ry protein kinase ATP la 2 ADP P tio Active protein n PP kinase ca Pi 2 sc ad Inactive protein kinase ATP e ADP P 3 Active protein PP kinase Pi 3 Inactive PP = Phosphatase protein ATP P ADP Active Cellular protein response PP Pi  Amplification Amplification increases the magnitude of each step as a signal transduction pathway proceeds Each activated enzyme in a pathway can activate hundreds of proteins (enzymes) in the next step in the pathway The more enzyme-catalyzed steps in a response pathway, the greater the amplification As a result, just a few extracellular signal molecules binding to their receptors can produce a full internal response Amplification in Signal Transduction [Insert Fig. 4.25 on p. 95] Fig. 4.25  Example: Stimulation of glycogen breakdown in liver cells by epinephrine Sutherland (Nobel Prize) Secretion of hormone epinephrine by adrenal gland  leads to increase in blood glucose hormone is first messenger leads to formation of second messenger Involves phosphorylation by kinases Adrenaline leads to several different physiological responses The “fight or flight” response includes several different cellular responses: Burst of energy from release of glucose into the bloodstream Released from glycogen stores in the liver Increased heart rate Dilated pupils Longer-lived responses include changes in the expression of some genes in some cell types How does one signal lead to multiple responses? Chapter 5  Oxidation-Reduction (Redox) Reactions Chemical reactions in which electrons are transferred from one atom or molecule to another LEO the lion says GER Loss of Electrons = Oxidation Gain of Electrons = Reduction  Electron Sharing The gain or loss of an electron in a redox reaction is not always complete Sometimes only the degree of electron sharing in covalent bonds changes (a relative loss or gain of electrons) Example: When methane burns, carbon loses a relative share of electrons, and oxygen gains a relatively larger share  Oxidation The partial or full loss of electrons from a substance The substance from which the electrons are lost (the e- donor) is oxidized Glucose Oxidation Carbon dioxide Dark shading represents increased electron density. Carbon atoms share Carbon atom has partially lost electrons (and is electrons equally. therefore oxidized) because the oxygen atom is more electronegative than the carbon atom.  Reduction The partial or full gain of electrons to a substance The substance that gains the electrons (the e- acceptor) is reduced Reduction Oxygen Water Sometimes electrons that are lost/gained are accompanied by protons (H+) Oxygen atoms share Oxygen atom has partially gained electrons (and electrons equally. therefore has been reduced) because the oxygen atom is more electronegative than the hydrogen atom.  A Redox Reaction Redox reactions are coupled reactions: The oxidation reaction and the reduction reaction occur simultaneously [Insert Fig. 5.3 on p. 103] Fig. 5.3  Combustion and Cellular Respiration [Insert Fig. 5.4 on p. 104] Cellular respiration is controlled combustion Fig. 5.4 Electron Carrier NAD+ [Insert Fig. 5.5 on p. 104] NAD+ is the oxidized form of an electron carrier. Two electrons and a proton are added to produce the reduced form, NADH. Fig. 5.5  Oxidation-Reduction Reactions Reduction reactions: NAD+ + 2e- + H+  NADH FAD + 2e- + 2H+  FADH2 Oxidation reactions: NADH  NAD+ + 2e- + H+ FADH2  FAD + 2 e- + 2H+  Cellular Respiration C6H12O6 + 6O2  6CO2 + 6H2O + energy Glucose Oxygen Carbon Water dioxide Cellular Respiration: Three Stages 1. Glycolysis (cytosol) 2. Pyruvate oxidation and the citric acid cycle (mitochondria) 3. Oxidative phosphorylation (mitochondria) Fig. 5.6 Mitochondria Most reactions of cellular respiration take place in mitochondria. Fig. 5.7, p. 113 Reactions of Glycolysis Glycolysis is a universal and ancient metabolic process [Insert Fig. 5.9 on p. 106] Glycolysis occurs in cytosol of all cells, and involves a series of soluble enzymes Fig. 5.9, p. 106  Glycolysis summary Glycolysis does not require O2 Series of 10 chemical reactions, each catalyzed by a different enzyme, and that can be grouped into an ”energy investment” phase, and an “energy payoff” phase” Converts glucose (6 carbons) into two molecules of pyruvate (3 carbons each) Fig. 5.8  Reactions of Glycolysis First ATP consuming reaction Second ATP consuming reaction Cleavage of 6 carbon sugar to two 3-carbon molecules Pyruvate (2 molecules) Fig. 5.9 Glycolysis Don’t expect memorization of the steps (i.e. all substrates, intermediates, enzymes) Do expect you to know: Where in the cell it takes place Key inputs (e.g. glucose, ATP, NAD+) Key outputs (pyruvate, ATP, NADH) Overall phases Understand what types of reactions are taking place at different steps of the pathway (e.g. redox, anabolic, catabolic, phosphorylation) One key enzyme Phosphofructokinase catalyzes the second ATP-consuming step of the pathway  ATP ATP molecules Produced in glycolysis Result from substrate-level phosphorylation Substrate-level phosphorylation Enzyme-catalyzed reaction Transfers phosphate group from substrate to ADP Substrate-Level Phosphorylation A phosphate group [Insert Fig. 5.10 on p. 108] is transferred from a high-energy donor directly to ADP, forming ATP Fig. 5.10, p. 108  Cellular Respiration Catabolism CO2 Carbohydrate Substrate-level phosphorylation Electron carriers Substrate-level Oxidative Electron producesphosphorylation phosphorylation only atransport small amount of the ATP chain ATP generated in cellular respiration O2 H2O  Cellular Respiration Catabolism CO2 Carbohydrate Substrate-level phosphorylation Electron carriers Oxidative Electron phosphorylation transport ATP chain Most of the ATP produced during cellular respiration is generated during oxidative phosphorylation. O2 H2O  Pyruvate Oxidation Takes place in mitochondria Pyruvate (3C) is oxidized to an acetyl group (2C) CO2 is produced Electrons removed are accepted by (or used to reduce) NAD+ to form NADH Acetyl group linked to Co-Enzyme A (CoA) Fig. 5.11, p. 108  Pyruvate Oxidation Pyruvate oxidation converts pyruvate to Pyruvate oxidation occurs within acetyl-CoA. This process is aerobic. the mitochondrial matrix Cytosol Matrix Intermembrane space NAD+ NADH + H+ Pyruvate Acetyl-CoA Coenzyme A CO2  Pyruvate Oxidation Each pyruvate molecule produces 1 acetyl group 1 NADH 1 CO2 Acetyl groups attached to coenzyme A Delivered to citric acid cycle Pyruvate oxidation links glycolysis and the citric acid cycle Amino Fatty Glucose acids acids At the End of Glycolysis ATP Pyruvate Oxidation Pyruvate Pyruvate 1 pyruvate molecule yields: CO2 Acetyl-CoA Acetyl-CoA 1 acetyl-CoA 1 CO2 Citric acid 1 NADH cycle CO2 ATP During glycolysis, glucose Electron produced 2 pyruvate molecules carriers 2 acetyl-CoA Electron transport chain O2 2 CO2 H2O 2 NADH ATP  Citric Acid Cycle Acetyl groups completely oxidized to CO2 Electrons removed in a series of oxidations Accepted by NAD+ or FAD (which get reduced to NADH And FADH2) Some ATP made by substrate-level phosphorylation Fig. 5.12, p. 109  Citric Acid Cycle Each acetyl group that enters the cycle and gets oxidized produces 2 CO2 1 ATP 3 NADH 1 FADH2  Summary of Citric Acid Cycle The eight reactions of the citric acid cycle (tricarboxylic acid cycle or Krebs cycle) oxidize acetyl groups completely to CO2, generate 3 NADH and 1 FADH2, and synthesize 1 ATP by substrate-level phosphorylation 1 acetyl-CoA + 3 NAD+ + 1 FAD + 1 ADP + 1 Pi + 2 H2O → 2 CO2 + 3 NADH + 1 FADH2 + 1 ATP + 3 H+ + 1 CoA Citric Acid Cycle [Insert Fig. 5.13 on p. 110] Fig. 5.13, p. 110 Amino Fatty Glucose acids acids At the End of Glycolysis ATP Citric Acid Cycle Pyruvate CO2 Acetyl-CoA Acetyl-CoA 2 molecule of acetyl-CoA yields: 2 ATP Citric acid cycle 6 NADH CO2 ATP 2 FADH2 Electron carriers Electron O2 transport chain H2O ATP Electron Transfer System and Oxidative Phosphorylation The electron transport chain converts the potential energy in NADH and FADH2 into a proton-motive force, which is used to drive ATP synthesis Fig. 5.14, p. 111 Electron Carriers During stage 3, oxidative phosphorylation, the reduced electron carriers generated in stages 1-2 donate electrons to the electron transport chain and a large amount of ATP is produced.  Electron Carriers Stage 1 Glycolysis Stages 1 - 2: Stage 2 Glucose is oxidized through a Pyruvate series of chemical reactions, oxidation releasing energy in the form of and ATP and reduced electron carriers. Citric acid cycle Stage 3: Electron carriers donate electrons Stage 3 to the electron transport chain, Oxidative leading to the synthesis of ATP. phosphory- lation  Electron Transfer System Electrons pass from NADH2 and FADH2 to O2 Electron Transport Chain includes 4 protein complexes 2 smaller shuttle carriers Electrons move spontaneously along the electron transport chain Fig. 5.14, p. 111  Respiratory Electron Transport Chain 3 major protein complexes (I, III, and IV) Pump H+ from Matrix to IMS Contain prosthetic groups that cycle between reduced and oxidized states Electrons Depleted of energy Delivered to oxygen as final electron acceptor Fig. 5.15, p. 112  Electron Transport Chain The complete oxidation of glucose during stages 1-2 of cellular respiration results in the production of the reduced electron carriers, NADH and FADH2. Energy stored in these electron carriers will be used to synthesize ATP. Mitochondrial matrix H+ NADH 4 H+ H+ ADP+ Pi ATP NAD+ + 2 H2O Complex I 2H+ FADH2 FAD + H+ ATP H+ O2 synthase H+ H+ Complex III e- e- Complex II e- e- Inter CoQ CoQ e- Complex IV Cytochrome c membrane H+ H+ H + H+ Intermembrane space  Electron Transport Chain The electron transport chain consists Electrons donated by NADH and of four complexes (I to IV) in the inner FADH2 are transported along the mitochondrial membrane. series of ETC complexes Mitochondrial matrix H+ NADH 4 H+ H+ ADP+ Pi ATP NAD + + 2 H2O Complex I 2H+ FADH2 FAD + H+ ATP H+ O2 synthase H+ H+ Complex III e- e- Complex II e- e- nter CoQ CoQ e- Complex IV Cytochrome c membrane H+ H+ H+ H+ Intermembrane space  Electron Transport Chain Electron transport Complexes I and II harvest electrons from NADH and FADH2. NADH 4 H+ H+ 2 H2O NAD+ + Complex I 2H+ FADH2 FAD + ATP Complex III O2 synthase e- e- Complex II e- e- CoQ CoQ e- Complex IV Cytochrome c Coenzyme Q (or Ubiquinone) is reduced Cytochrome c moves to complex to CoQH2 and transfers electrons from IV where oxygen is reduced to complexes I and II to complex III. form water.  Electron Transport Chain Electron transport NADH 4 H+ H+ 2 H2O NAD+ + Complex I 2H+ FADH2 FAD + ATP Complex III O2 synthase e- e- Complex II e- e- CoQ CoQ e- Complex IV Cytochrome c Within each protein complex of the When oxygen accepts electrons ETC, electrons are passed from at the end of the ETC, it is electron donors to electron acceptors. reduced to form water.  Electron Transport Chain Proton transport and ATP synthesis The transport of electrons in complexes I, III, and IV ATP synthase uses the is coupled with the transport of protons across the electrochemical proton inner membrane, from the mitochondrial matrix to gradient to drive the the intermembrane space. synthesis of ATP. Mitochondrial matrix H+ ADP + Pi ATP Complex I ATP H+ H+ synthase H + Complex III H + Complex II Complex IV CoQ CoQ Cytochrome c H+ H+ H+ H+ Intermembrane space  Electron Transport Chain Proton transport and ATP synthesis Due to the proton pumping of the ETC, protons have a high concentration in the intermembrane space and a low concentration in the mitochondrial matrix. The proton concentration gradient contains high potential energy. Mitochondrial matrix H+ ADP + Pi ATP Complex I Proton concentration ATP H+ H+ synthase H H+ Complex III + gradient Complex II Complex IV CoQ CoQ Cytochrome c H+ H+ H+ H+ Intermembrane space Oxidative Phosphorylation and Chemiosmosis ATP synthase catalyzes ATP synthesis using energy from the H+ gradient across the membrane (chemiosmosis) ATP synthase Molecular motor Embedded in inner mitochondrial membrane with electron transfer system ATP synthase converts the energy of the proton gradient into the energy of ATP Fig. 5.16, p. 112 Oxidative Phosphorylation Understanding the difference between: Electron Transport Chain Proton-motive force Chemiosmosis ATP Synthase Oxidative Phosphorylation  Uncoupling of Electron Transport and ATP Synthesis Electron transport and chemiosmotic generation of ATP are separate and distinct processes [Insert Fig. 5.17 on p. 114] Fig. 5.17, p. 114 ATP Yield from the Oxidation of Glucose C6H12O6 + 6O2 6CO2 + 6H2O + energy Glycolysis Pyruvate oxidation Citric acid cycle ETC Fig. 5.18, p. 115  Major Pathways Oxidizing Carbohydrates, Fats, and Proteins Besides simple sugars, energy can be extracted from fats, proteins, and carbohydrates that enter the respiratory chain at different points Fig. 5.19, p. 116  Respiratory Intermediates Intermediates of glycolysis and the citric acid cycle are routinely diverted and used as starting substrates to synthesize amino acids, fats, and the pyrimidine and purine bases needed for nucleic acid synthesis Respiratory intermediates also supply the carbon backbones for hormones, growth factors, prosthetic groups, and cofactors essential to cell function  Control of Cellular Respiration [Insert Fig. 5.20 on p. 117] A number of different molecules can activate and repress key steps of the respiratory pathway so that it can be controlled by supply and demand Fig. 5.20, p. 117  Dependency upon Presence of Oxygen In anaerobic respiration, the terminal electron acceptor is not oxygen [Insert Fig. 5.21 on p. 117] Fig. 5.21, p. 117  Fermentation In eukaryotic cells, low oxygen levels result in fermentation Fermentation is the pathway of respiration that oxidizes fuel molecules in the absence of oxygen Two types of fermentation exist: lactate fermentation and alcohol fermentation  Fermentation Glucose Lactic acid Glycolysis fermentation anaerobic Pyruvate When oxygen is Ethanol present, pyruvate is aerobic fermentation converted to acetyl- Pyruvate CoA, which then enters oxidation the citric acid cycle, followed by the ETC. Acetyl CoA When oxygen is not Citric present, pyruvate is acid cycle metabolized along a number of different Electron transport pathways. chain (ETC) and oxidative phosphorylation  Fermentation [Insert Fig. 5.22 on p. 118] NAD+ produced in The breakdown of glucose by fermentation yields fermentation is only 2 molecules of ATP, since lactic acid and ethanol are not fully oxidized and still contain a used in glycolysis. large amount of chemical energy in their bonds. Fig. 5.22, p. 118 Lactate Fermentation Lactic acid fermentation occurs in animals and bacteria. Electrons from NADH are transferred to pyruvate to produce lactic acid and NAD+. Fig. 5.22a, p. 118 Alcoholic Fermentation Ethanol fermentation occurs in plants and fungi Electrons from NADH are transferred to pyruvate to produce ethanol and NAD+. Fig. 5.22b, p. 118  Anaerobic Respiration Although they lack mitochondria, many bacteria and archaea have respiratory electron transport chains, located on internal membrane systems Some use a molecule other than O2 as terminal electron acceptor Possess anaerobic respiration Sulfate, nitrate, and ferric ion are common electron acceptors  Lifestyles Dictated by Oxygen Strict anaerobes: Cannot grow in presence of oxygen Strict aerobes: Require oxygen Facultative aerobes: Can grow in presence of oxygen and can grow using fermentative pathways  Paradox of Aerobic Life Although many organisms cannot exist without oxygen because it is required for electron transport, oxygen itself is inherently dangerous to all forms of life Reactive oxygen species (ROS) Include superoxide and hydrogen peroxide Strong oxidizing agents Reduction of Oxygen to Water [Insert Fig. 5.24 on p. 119] The conversion of O2 to water is stepwise, resulting in the formation of the intermediate ROS, which are potentially harmful Fig. 5.24, p. 119  Defence against Reactive Oxygen Species Antioxidant defence system Enzymes Superoxide dismutase and catalase Nonenzymes Antioxidants: vitamin C and vitamin E