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1 Mobile phone rings during class Be late Chat during class Slide 2 2 Dr Lihong Xu( Prof of Biochemistry and Molecular Biology xulihong@zju.edu.cn Slide 3 3 III. Metabolic pathways, their regulation and metabolic interrelationships I. Biomolecules II. Enzymes IV. Hormones V. Fat soluble and water soluble vitamins VI. Hematic Biochemistry VII. Molecular Biology Slide 4 4 Slide 5 5 We are the most important organism in the earth. T or F ? Slide 6 6 nitrogen Cycling of nitrogen in the biosphere We are here. N2N2 Amino acids NO 3 - NO 2 - NH 3 nitrogen-fixing bacteria nitrifying bacteria denitrifying bacteria mammals plants Urea animals Slide 7 7 carbon dioxideoxygen autotrophic heterotrophic Cycling of carbon dioxide and oxygen between the autotrophic (photosynthetic) and heterotrophic domain in the biosphere. glucose autotrophic photosynthetic (autotrophic) heterotrophic O 2, organic products CO 2 We are here. Slide 8 8 Phototrophs synthesize its own fuels Phototrophs, an organism that can use the energy of light to synthesize its own fuels from simple molecules such as CO 2, O 2, and H 2 O, as distinct from a chemotroph. photosynthesis Autotrophs, synthesize its own complex molecules Autotrophs, an organism that can synthesize its own complex molecules from very simple carbon and nitrogen sources, such as CO 2 and NH 3. Can we do these? Slide 9 9 Chemotroph from other organisms Chemotroph, an organism that obtains energy by metabolizing organic compounds derived from other organisms. HOW do we get the energy and the building blocks of macromolecules? Phototrophs Autotrophs. We, animal, live on Phototrophs and Autotrophs. We can eat. We must eat. Slide 10 10 III-I Metabolism III-II Carbohydrate metabolism III-III Lipid metabolism III-IV TCA cycle and biological oxidation III-V Protein turnover and amino acid metabolism ; Nucleotide metabolism III - VI Regulation of the metabolic pathways III. Metabolic pathways, their regulation and metabolic interrelationships Slide 11 11 Digestion and absorption of dietary carbohydrates Pathways of glucose metabolism: glycolysis Pentose phosphate shunt Gluconeogenesis Glycogenolysis, glycogenesis Galactose and fructose metabolism Glycogen storage disease Inborn errors of glucose metabolism Regulation of glucose metabolism. Digestion and absorption of dietary protein General reactions, transamination, its metabolic and diagnostic significance Disposal of amino acid nitrogen and detoxication of urea Metabolic fate of amino acid carbon skeleton Sulphur containing amino acids In born errors of branched chain and aromatic amino acids Important amino acid derivatives. Nucleotide metabolism Digestion and absorption of dietary fats. Biosynthesis and degradation of fatty acids, phospolipids and triacylglycerols Biosynthesis of cholesterol, chemistry and metabolism of lipoproteins. Hyperlipoproteinemias Lipid storage disease. Ketone bodies: their synthesis, utilization and conditions leading to ketoacidosis, prostaglandin. Carbohydrate, lipid and amino acid metabolism Interlinks between these pathways. Organ interrelationships in metabolism, Blood glucose regulation, and its impairment in diabetes mellitus. Metabolic adaptation in the fed state, fasting and prolonged starvation. Metabolic derangements and adaptations in diabetes mellitus. general concepts and characteristics of metabolic pathways. III-I Metabolism III-II Carbohydrate metabolism III-III Lipid metabolism III-IV TCA cycle and biological oxidation III-V Protein turnover and amino acid metabolism ;Nucleotide Metabolism III-VI Regulation of the metabolic pathways Slide 12 12 III-II Carbohydrate metabolism III-III Lipid metabolism III-V Protein turnover and amino acid metabolism III-IV TCA cycle and biological oxidation III-VI Regulation of the metabolic pathways III-I Metabolism Slide 13 13 III-I Metabolism general concepts and characteristics of metabolic pathways Slide 14 14 AQ what why how Be sure to REMEMBER Slide 15 15 Q energy Where do we get energy ? building blocks of macromolecules Where do we get building blocks of macromolecules to build ourself? Slide 16 16 ENERGY RICH MOLECULES, produced by autotrophs and phototrophs, as well as other chemotrophs We,human beings and animals,obtain energy and building blocks of macromolecules from ENERGY RICH MOLECULES, produced by autotrophs and phototrophs, as well as other chemotrophs polysaccharideslipidsprotiens nutrients A amino acidsmonosaccharides glycerol fatty acids Thousands of complex reactions vitamins minerals Slide 17 17 Thousands of complex reactions Chemical reactions Catalyzed by enzymes CELL Certain compartment in the CELL Energy Building blocks Other molecules needed in the body To be alive How can the reactions happen? Slide 18 18 In a reversible reaction, what will decide the direction of the reaction ? ABC Cell, isothermal + Slide 19 19 Free energy (G) indicative of the spontaneity of a process. A thermodynamic quantity, whose change at constant pressure is indicative of the spontaneity of a process. Free-energy change (G) released absorbedreaction The amount of free energy released (negative G) or absorbed (positive G) in a reaction at constant temperature and pressure. Basic concepts Slide 20 20 FREE ENERGY The energy that cells can and must use is FREE ENERGY, a continual input FREE ENERGY Living organisms require a continual input of FREE ENERGY Slide 21 21 G G will determine whether the reaction will be spontaneous whether the reaction will be spontaneous at constant temperature and pressure. G What does G mean? Q A Slide 22 22 Units of energy Units of energy (will be used in description of free energy) A calorie (cal) is equivalent to the amount of heat required to raise the temperature of 1 gram of water from 14.5C to 15.5C. kcal A kilocalorie (kcal) is equal to 1000 cal. A joule (J) is the amount of energy needed to apply a 1-newton force over a distance of 1 meter. kJ A kilojoule (kJ) is equal to 1000 J. 1 kcal = 4.184 kJ Slide 23 23 Change in free energy ( G) during a reaction. A can be spontaneously converted into B B cannot be spontaneously converted into A unfavorable process favorable process Slide 24 24 1. A reaction can occur spontaneously only if G is negative. Such reactions are said to be exergonic. 2. A system is at equilibrium and no net change can take place if G is zero. 3. A reaction cannot occur spontaneously if G is positive. An input of free energy is required to drive such a reaction. These reactions are termed endergonic. Slide 25 25 A thermodynamically unfavorable reaction can be COUPLED by a thermodynamically favorable reaction. How is the free energy inputted to drive a reaction with positive G? Q A Slide 26 26 coupled Favorable and unfavorable processes could be coupled Slide 27 27 mechanica chemical Energy coupling in mechanical and chemical processes Slide 28 28 chemically coupled The overall free-energy change for a chemically coupled series of reactions is equal to the sum of the free-energy changes of the individual steps. intermediate B the chemical intermediate B, common to both couples the reactions reactions, couples the reactions. Slide 29 29 unfavorable DRIVEN favorablecoupled. A thermodynamically unfavorable reaction can be DRIVEN by a thermodynamically favorable reaction to which it is coupled. overall G as long as overall G is negative. Slide 30 30 ATP and other energy-carrier compounds The cell uses ATP and other energy-carrier compounds, transformed from FREE ENERGY. HOW does the cell use FREE ENERGY? transform Both chemotrophy and phototrophy (as well as autotrophy) transform the free energy into ATP and other energy-carrier compounds. Q A Slide 31 31 The First Law of Thermodynamics neither creatednor destroyed The energy can be neither created nor destroyed. energy in the universe is constant The amount of energy in the universe is constant. converted from one form into another The energy can be converted from one form into another. Slide 32 32 Basic concepts ATP adenine adenosine Adenosine monophosphate, AMP Adenosine diphosphate, ADP Adenosine triphosphate, ATP Slide 33 33 phosphoanhydride bonds, high-energy phosphate bonds phosphoanhydride bonds. ATP is an energy-rich molecule because its triphosphate unit contains two phosphoanhydride bonds. phosphate group transfer potential Slide 34 34 free energy is liberated when ATP is hydrolyzed A large amount of free energy is liberated when ATP is hydrolyzed to ADP + Pi or AMP + PPi exergonic Slide 35 35 only if ATP is continually regenerated from ADP Motion, active transport, signal amplification, and biosynthesis can occur only if ATP is continually regenerated from ADP. ATP ADP cycle energy exchange a fundamental model of energy exchange in biological system Slide 36 36 There are two ways to form ATP. Substrate Level Phosphorylation Oxidative Phoshorylation Q A Slide 37 37 Is ATP the only energy-carrier compound ? There are some phosphorylated compounds ranking to energy-carrier compounds, like. (filled it by youself) Q A Slide 38 38 Phosphate group transfer potential The tendency of a phosphorylated molecule to undergo hydrolysis energy is released During its hydrolysis, energy is released. cellular energy transformation The phosphoryl transfer potential is an important form of cellular energy transformation. Basic concepts Slide 39 39 ATP is not the only compound with a higy phosphoryl transfer potential. other energy-carrier compounds Glycolysis intermediate Slide 40 40 Why is ATP the most important energy- carrier compound ? energy currency. ATP is highly accessible for energy- requiring processes, called energy currency. Q A Slide 41 41 to phosphorylate ADP to form ATP Some compounds have a higher phosphoryl transfer potential than that of ATP and can be used to phosphorylate ADP to form ATP. Slide 42 42 Slide 43 43 intermediate among the biologically important phosphorylated molecules. It is significant that ATP has a phosphate group transfer potential that is intermediate among the biologically important phosphorylated molecules. carrier of phosphoryl groups This intermediate position enables ATP to function efficiently as a carrier of phosphoryl groups. Slide 44 44 Importance of ATP during exercise ATP less than a second The amount of ATP in muscle suffices to sustain contractile activity for less than a second. Creatine phosphate ATP regeneration first 4 seconds Creatine phosphate is the major source of phosphoryl groups for ATP regeneration for a runner during the first 4 seconds of a 100-meter sprint, regenerated The ATP must be regenerated by metabolic pathways. more rapidly more efficiently Slide 45 45 ATP other energy-carrier compounds HOW is the free energy transformed into ATP and other energy-carrier compounds The free energy is transformed into ATP and energy-carrier compounds through metabolism of nutrient molecules metabolism of nutrient molecules. Q A Slide 46 46 building blocks HOW do we get building blocks of macromolecules for our body? metabolism of nutrient molecules The build blocks is derived from metabolism of nutrient molecules. Q A Slide 47 47 pathway is reactionsoverall free energy of the pathway is negative. is formed by the coupling of enzyme-catalyzed reactions such that the overall free energy of the pathway is negative. Specific pathwaysindividual reactions Specific pathways constructed from individual reactions must satisfy minimally two criteria: specific.the individual reactions must be specific. thermodynamically favoredthe entire set of reactions that constitute the pathway must be thermodynamically favored. enzyme overall G overall G is negative Basic concepts The product of one reaction is the substrate of subsequent reaction. Slide 48 48 catabolic pathways catabolic pathways capture chemical energy ATP reducing power convert building blocks serve to capture chemical energy in the form of ATP from the degradation of energy-rich fuel molecules, as well as extract reducing power from the diet, convert molecules in the diet into building blocks needed for the synthesis of complex molecules. Basic concepts Slide 49 49 anabolic pathways anabolic pathways small molecules the energy and reducing power are needed combine small molecules to form complex molecules, in which the energy and reducing power are needed, supplied in the form of ATP and NADPH respectively. Basic concepts chemical reduction. Anabolic reactions often involve chemical reduction. Slide 50 50 Most catabolic pathways involve coupled to generation of both energy (ATP) and reducing power (NADH). the oxidation of organic molecules coupled to the generation of both energy (ATP) and reducing power (NADH). use of both ATP and reducing power NADPH In contrast, anabolic pathways generally involve the use of both ATP and reducing power (usually in the form of NADPH) for the production of new organic compounds. NADH NADPH Slide 51 51 NADP and NAD NAD, without -PO 4 2- coenzyme Slide 52 52 Slide 53 53 catabolic anabolic Energy relationships between catabolic and anabolic pathways Slide 54 54 Metabolism Metabolism pathways networkof chemical reactions different pathways intersect, forming an integrated and purposeful network of chemical reactions Basic concepts Slide 55 55 map of metabolism Slide 56 56 map of metabolism Slide 57 57 Thousands of metabolic reactions can be subdivided into just six types. Slide 58 58 Where do we get nutrients? carbohydrateslipidsproteins We obtain carbohydrates, lipids, proteins, main energy-providing compounds, and other nutrients from foodstuff. Q A Slide 59 59 Carbohydrateslipidsproteins Slide 60 60 What is the general process to extract energy from foodstuffs? There are three stages in catabolism. Q A Slide 61 61 No useful energy is captured in this phase Large molecules in food are broken down into smaller units. No useful energy is captured in this phase. Some ATP is generated in this stage These numerous small molecules are degraded to a few simple units that play a central role in metabolism. Some ATP is generated in this stage. ATP is produced ATP is produced from the complete oxidation of the acetyl unit of acetyl CoA, the final common pathways in the oxidation of fuel molecules. Three stages in the generation of energy from the oxidation of foodstuffs Cell Slide 62 62 Main topics in the Part III Slide 63 63 Summary Summary for the chapter The energy that cells can and must use is free energy. G will determine whether the reaction will be spontaneous at constant temperature and pressure. A thermodynamically unfavorable reaction can be coupled by a thermodynamically favorable reaction. There are some phosphorylated compounds ranking to energy-carrier compounds Slide 64 64 The free energy is transformed into ATP and energy- carrier compounds through metabolism of nutrient molecules. The build blocks of macromolecules are derived from metabolism of nutrient molecules. We obtain carbohydrates, lipids, proteins, main energy-providing compounds, and other nutrients from foodstuff. There are three stages in catabolism. ATP is highly accessible for energy-requiring processes, called energy currency. Slide 65 65 Summarize QA & by yourself