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Metabolism: Fueling Cell Growth Chapter 6 Metabolism Cells must accomplish two fundamental tasks to grow Synthesize new components Biosynthesis Harvest energy The sum total of chemical reactions of biosynthesis and energy-harvesting is termed metabolism Principles of Metabolism Metabolism is broken down into two components Anabolism Catabolism Catabolism Degradative reactions Reactions produce energy from the break down of larger molecules Anabolism Reactions involved in the synthesis of cell components Anabolic reactions require energy Anabolic reactions utilize the energy produced from catabolic reactions Principles of Metabolism Harvesting energy Energy defined as capacity to do work Exists as Potential energy Stored energy Kinetic energy Energy in motion Doing work Energy can be converted from one form to another Potential kinetic Kinetic potential Principles of Metabolism Harvesting energy Amount of energy available released from bonds is free energy Energy available to do work If reactants have more free energy than products, energy is released Exergonic reaction If products have more energy that reactants, energy is consumed Endergonic reaction Principles of Metabolism Components of metabolic pathways Process occurs in sequence of chemical reactions Starting compound is converted to intermediate molecules and end products Intermediates and end products can be used as precursor metabolites Metabolic pathways employ critical components to complete processes Enzymes ATP Chemical energy source Electron carriers Precursor metabolites Principles of Metabolism Role of enzymes Enzymes facilitate each step of metabolic pathway They are proteins acting as chemical catalysts Accelerate conversion of substrate to product Catalyze reactions by lowering activation energy Energy required to initiate a chemical reaction Principles of Metabolism Role of ATP Adenosine triphosphate (ATP) Energy currency of cell Negatively charged phosphate groups attached to adenosine molecule Negative charges of phosphate repel Create unstable bond that is easily broken releasing energy ATP created by three mechanism Substrate phosphorylation Oxidative phosphorylation Photophosphorylation Principles of Metabolism Substrate phosphorylation Uses chemical energy to add phosphate ion to molecule of ADP Oxidative phosphorylation Uses energy from proton motive force to add phosphate ion to ADP Photophosphorylation Utilizes radiant energy from sun the phosphorylate ADP to ATP Principles of Metabolism Role of chemical energy source Energy source Compound broken down to release energy Variety of compounds available Glucose most common organic molecule Harvesting energy requires series of coupled reactions Oxidation-reduction reactions Principles of Metabolism Oxidation-reduction reactions Reactions in which one or more electrons is transferred from one substance to another Compounds that LOSE electrons are oxidized Termed electron donor Compounds that GAIN electrons are reduced Termed electron carrier In reactions electrons are removed Protons often follow generally in the form of H+ ion H+ ion has one proton and no electron Principles of Metabolism Role of electron carriers Three different types of electron carriers Nicotinamide adenine dinucleotide NAD+ Flavin adenine dinucleotide FAD Nicotinamide adenine dinucleotide phosphate NADP+ Reduced forms represent reducing power Due to usable energy in bonds Reduced forms NADH FADH2 NADPH Principles of Metabolism Precursor metabolites Intermediate products produced in catabolic pathways Used in anabolic pathways Serve as raw materials for construction of macromolecules Principles of Metabolism Scheme of metabolism Three key pathways Central metabolic pathways Glycolysis Pentose phosphate pathway Tricarboxcylic acid cycle Central pathways are catabolic and provide Energy Reducing power Precursor metabolites Principles of Metabolism Glycolysis Oxidizes glucose to two molecules of pyruvate Pentose phosphate pathway (PPP) Breaks down glucose Produces molecules for biosynthesis Works in conjunction with glucose degrading pathways Tricarboxylic acid cycle (TCA) Krebs Cycle Before entering cycle pyruvate enters transition step Pyruvate formed in glycolysis and PPP Cycle turns twice to complete oxidation of one glucose molecule Principles of Metabolism Respiration vs. fermentation Respiration uses reducing power to generate ATP NADH and FADH2 transfer electrons to produce proton motive force Allows for recycling of electron carriers Electrons join with terminal electron acceptor Oxygen in aerobic respiration Anaerobic respiration uses another inorganic molecule Fermentation is partial oxidation of glucose Produces very little ATP Uses pyruvate or derivative as terminal electron acceptor Other organisms may use other organic molecules as terminal electron acceptor Enzymes Act as biological catalysts Very specific A particular enzyme will only act with one or a limited number of substrates Enzymes do not alter the reactants or products of a chemical reaction Enzymes are not altered by the chemical reaction they catalyze Enzymes are usually named for the substrate they act on and end in the suffix –ase Protease Enzymes Enzyme action Enzymes act in two steps Substrate binds to the active site of the enzyme to form an enzyme/substrate complex A substrate is the specific substance on which the enzyme acts Products are formed E + S ES E + P Enzyme is released to bind new substrate Enzymes are regulated to prevent over production of product Enzymes Cofactors and coenzymes Cofactors Non-protein component reacting with enzyme Coenzymes Organic cofactors Act as carriers for molecules or electrons NAD+, FAD and NADP+ are coenzymes Not as specific as enzymes May act with numerous enzymes Enzymes Environmental factors of enzyme activity Enzymes function in narrow range of environmental factors Factors affecting enzyme activity are Temperature Increases temperature increases speed of reaction Extremely high temperature makes enzyme non functional pH Enzymes function best at pH just above 7 Salt concentration Low salt concentration are most desired Enzymes Allosteric regulation Regulation regulates production of product Regulatory molecule binds to allosteric site of enzyme Alters affinity of enzyme to substrate Allosteric enzymes initiates activity of give pathway Regulation controls metabolic activity Feedback inhibition End product of pathway acts on allotter site of enzyme Shuts pathway down Enzymes Enzyme inhibition Non-competitive inhibition Inhibitor and substrate act on different enzyme sites Allosteric inhibition Feedback inhibition Competitive inhibition Inhibitor competes for active site with substrate Inhibitor structurally similar to substrate Sulfa drugs compete with PABA for active site on enzyme that produces folic acid Central Metabolic Pathways Pathways modify organic molecules to form High energy intermediates to synthesize ATP Intermediates to generate reducing power Intermediate and end products as precursor metabolites Pathways Glycolysis Pentose Phosphate Pathway Tricarboxylic Acid Cycle Central Metabolic Pathways Glycolysis Primary pathway to convert one glucose to two pyruvate 10 step process Pathway generates Two 3-C pyruvate molecules Net gain of two ATP 2 ATP expended to break glucose 4 ATP harvested Two molecules reducing power NADH Six different precursor metabolites 5 intermediates and pyruvate Glycolysis Central Metabolic Pathways Pentose phosphate pathway Generates 5 and 7 carbon sugars Also produces glyceraldehyde 3-phosphate Can go into glycolysis for further breakdown Pathway major contributor to biosynthesis Produces reducing power in NADPH Two vital precursor metabolites Central Metabolic Pathways Transition step Links glycolysis to Tricarboxylic Acid Cycle Modifies 3-C pyruvate from glycolysis to 2-C acetyl CoA CO2 is removed through decarboxylation Remaining 2-C acetyl group joined to coenzyme A Forms Acetyl CoA NAD+ is reduced to NADH Each pyruvate enters transition step Reaction occurs twice for one glucose Yield from transition step Reducing power NADH Precursor metabolites Acetyl CoA Central Metabolic Pathways Tricarboxylic acid cycle Completes the oxidation of glucose Incorporates acetyl CoA from transition step Releases CO2 in net reaction Cycle turns once for each acetyl CoA Two turns for each glucose molecule Cycle produces 2 ATP 6 NADH 2 FADH2 2 precursor metabolites Tricarboxylic Acid Cycle Respiration Uses NADH and FADH2 to synthesize ATP Oxidative phosphorylation Occurs in electron transport chain Generates proton motive force Combined with ATP synthase Uses energy in proton motive force to synthesize ATP Respiration Electron transport chain Group of membrane-embedded electron carriers Arrangement of carriers aids in production of proton motive force Four types of electron carriers Flavoproteins Iron-sulfur proteins Quinones Cytochromes Respiration Mechanism of proton motive force Certain carriers accept protons and electrons, some accept only electrons Pump protons across membrane Creates a proton gradient (proton motive force Arrangement of carriers causes protons to be shuttled across membrane Respiration Electron transport chain of mitochondria Chain consists of following components Complex I A.k.a NADH dehydrogenase complex Complex II A.k.a succinate dehydrogenase complex Coenzyme Q A.k.a cyrochiome bc, complex Complex III Cytochrome C A.k.a. Cyrochiome c oxidate complex Complex IV Each carrier accepts electrons from previous carrier In process protons are pumped across membrane Electron Transport Chain of Mitochondria Respiration Electron transport chain of prokaryotes Respiration is either aerobic or anaerobic In aerobic respiration some prokaryotes have enzymes equivalent to complex I and II of mitochondria Do not have enzyme equivalents of complex III or cytochrome c Use quinones instead (ubiquinone) Shuttles electrons directly to terminal electron acceptor Oxygen acts as acceptor when available Electron Transport Chain of Prokaryotes (Aerobic) Respiration Electron transport chain in prokaryotes Anaerobic respiration is less efficient Alternative electron carriers used Oxygen does not act as terminal electron acceptor Some bacteria use nitrate Nitrate converted to nitrite Nitrite converted to ammonia Sulfur-reduce bacteria use sulfate as terminal electron acceptor Quinone carrier (menaquinone) produces vitamin K Respiration ATP synthase Harvest energy from proton motive force to synthesize ATP Permits protons to flow back into cell Produces enough energy to phosphorylate ADP ATP 1 ATP is formed from entry of 3 protons 10 protons pumped out per NADH One NADH produces 3 molecules ATP 6 protons pumped out per FADH One FADH2 produces 2 molecules of ATP Respiration ATP from oxidative phosphorylation ATP produced through re-oxidation of NADH and FADH2 Maximum theoretical yield From glycolysis 2 NADH 6 ATP From transition step 2 NADH 6 ATP From TCA 6 NADH 18 ATP 2 FADH2 4 ATP Respiration Total ATP yield from prokaryotic aerobic respiration Substrate phosphorylation 4 ATP Net 2 from glycolysis 2 ATP from TCA Oxidative phosphorylation 34 ATP 6 ATP from glycolysis Re-oxidation of 2 NADH 6 from transition step Re-oxidation of NADH 22 from TCA cycle Re-oxidation of NADH and FADH2 Total yield 4 + 34 = 38 (theoretical maximum) Eukaryotic cells have theoretical maximum of 36 2 ATP spent crossing mitochondrial membrane Fermentation Used by organisms that cannot respire Due to lack of suitable inorganic electron acceptor or lack of electron transport chain ATP produced only in glycolysis Other steps for consuming excess reducing power Recycles NADH Fermentation pathways use pyruvate or derivative as terminal electron acceptor Fermentation End products of fermentation include Lactic acid Ethanol Butyric acid Propionic acid 2,3-Butanediol Mixed acids All are produced in a series of reaction to produce appropriate terminal electron acceptors Catabolism of Other Organic Compounds Cells use variety of organic molecules as energy sources Use hydrolytic enzymes to break bonds Hydrolytic reactions add water to break bonds Catabolism of Other Organic Compounds Polysaccharides and disaccharides Starch and cellulose polymers of glucose Amylases breaks down starch to glucose subunits Cellulases breaks down cellulose to glucose subunits Glucose enters glycolysis for metabolism Disaccharides are hydrolyzed by specific disaccharidases Disaccharides are formed between glucose and other monosaccharides Glucose liberated through hydrolysis enters glycolysis Other monosaccharide modified before metabolism Catabolism of Other Organic Compounds Lipids Simple lipids are combination of fatty acids and glycerol Hydrolyzed by lipases Glycerol is converted to dihydroxyacetone phosphate Molecule enters glycolysis Fatty acids degraded by β-oxidation Transfers 2-C fatty acid units to coenzyme A Forms acetyl CoA that enters TCA cycle Catabolism of Other Organic Compounds Proteins Hydrolyzed by proteases Amino group removed through deamination Remaining carbon skeleton converted to precursor metabolite Chemolithotrophs Chemolithotrophs able to reduce inorganic chemicals as source of energy Organisms fall into four groups Hydrogen bacteria Oxidize hydrogen gas Sulfur bacteria Oxidize hydrogen sulfide Iron bacteria Oxidized reduced iron Nitrifying bacteria Two groups One oxidizes ammonia to nitrite One oxidizes nitrite to nitrate Chemolithotrophs Chemolithotrophs generate ATP through oxidative phosphorylation Amount of energy gained depends on energy source and terminal electron acceptor Organisms thrive in specific environments Particularly where reduced inorganic compounds are found Do not require external carbon source Produce organic carbon from inorganic source through carbon fixation Photosynthesis Photosynthetic organisms harvest energy from sunlight Use energy to power synthesis of organic compounds from CO2 Photosynthesis has two distinct stages Light dependent reactions A.k.a light reactions Converts light energy to chemical energy Light independent reactions a.k.a dark reactions Uses energy from light reactions to produce organic compounds Photosynthesis Capturing radiant energy Photosynthetic organisms highly visible due to light capturing pigments Pigments include Chlorophyll Found in plants, algae and cyanobacteria Bacteriochlorophylls Found in purple and green photosynthetic bacteria Accessory pigments Includes carotenoids and phycobilins Carotenoids found in eukaryotes and prokaryotes Phycobilins found only in cyanobacteria Reaction center pigments Function as electron donors Antennae pigments Funnels light energy to reaction center pigments Photosynthesis Converting radiant energy to chemical energy Light reactions accomplish two tasks Synthesize ATP through photophosphorylation Generate reducing power to fix carbon dioxide Reducing power may be NADH or NADPH Light Dependant Reactions Carbon Fixation Carbon dioxide converted to organic carbon through carbon fixation Occurs in dark reactions in photosynthesis Consumes great deal of energy Calvin cycle most common pathway of carbon fixation Carbon fixation Calvin Cycle A.k.a Calvin-Benson cycle Has three essential stages One molecule of fructose produces from 6 turns of cycle Incorporation of CO2 into organic compound Reduction of resulting molecules Regeneration of starting compound 6 turns consumes 18 ATP and 12 NADPH Process has three sages Anabolic Pathways Synthesis of subunits from precursor metabolites Pathways consume ATP, reducing power and precursor metabolites Macromolecules produces once subunits are synthesized Anabolic Pathways Lipid synthesis Synthesis begins with transfer of acetyl group from acetyl CoA to acyl carrier protein Carrier hold fatty acid during elongation Fatty acid released when reaches required length 14, 16 or 18 carbons long Glycerol is synthesized from dihydroxyacetone phosphate Anabolic Pathways Amino acid synthesis Some precursors are formed in glycolysis other in TCA cycle Glutamate synthesis essential for formation of other amino acids Synthesis incorporates ammonia with αketoglutarate produce in TCA cycle Amino group from glutamate can be transferred to produced other amino acids Precursors for aromatic amino acids produced in pentose phosphate pathway and glycolysis Anabolic Pathways Nucleotide synthesis Nucleotides synthesized as ribonucleotides and modified to deoxribonucleotides Replace OH group on 2’ carbon of ribose and replace with hydrogen atom Remove oxygen