Be late Mobile phone rings during class Chat during class 1 Dr Lihong(立红) Xu(徐) Prof of Biochemistry and Molecular Biology 生物 化学与分子 生物学 教授 xulihong@zju.edu.cn 2 I. Biomolecules II. Enzymes √ √ III. Metabolic pathways, their regulation and metabolic interrelationships IV. Hormones V. Fat soluble and water soluble vitamins VI. Hematic Biochemistry VII. Molecular Biology 3 长城 西湖 4 We are the most important organism in the earth. T or F ? 5 N2 nitrogen-fixing bacteria NH3 Urea mammals denitrifying bacteria nitrifying bacteria animals plants Amino acids plants NO3- NO2Cycling of nitrogen 6 in the biosphere photosynthetic (autotrophic) heterotrophic Cycling of carbon dioxide and oxygen between the autotrophic (photosynthetic) and heterotrophic 7 domain in the biosphere. Phototrophs, an organism that can use the energy of light to synthesize its own fuels from simple molecules such as CO2, O2, and H2O, as distinct from a chemotroph. photosynthesis Autotrophs, an organism that can synthesize its own complex molecules from very simple carbon and nitrogen sources, such as CO2 and NH3. Can we do these? 8 We can eat. We must eat. Chemotroph, an organism that obtains energy by metabolizing organic compounds derived from other organisms. We, animal, live on Phototrophs and Autotrophs. HOW do we get the energy and the building blocks of macromolecules? 9 III. Metabolic pathways, their regulation and metabolic interrelationships 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 10 general concepts and characteristics of metabolic pathways. III-I Metabolism III-II Carbohydrate metabolism III-III III-IV III-V III-VI 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 fats. Biosynthesis and degradation of fatty acids, Lipid metabolism phospolipids and triacylglycerols TCA cycle and biological oxidation Biosynthesis of cholesterol, chemistry and metabolism of lipoproteins. Protein turnover and amino acid Hyperlipoproteinemias metabolism ;Nucleotide Metabolism Lipid storage disease. Ketone bodies: their synthesis, utilization Regulation of the metabolic pathways 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. 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 11 Important amino acid derivatives. Nucleotide metabolism 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 III-VI Regulation of the metabolic pathways 12 III-I Metabolism general concepts and characteristics of metabolic pathways 13 what Q why A how Be sure to REMEMBER 14 Q Where do we get energy ? Where do we get building blocks of macromolecules to build ourself? 15 beings and animals ,obtain energy and building A We,human blocks of macromolecules from ENERGY –RICH MOLECULES, produced by autotrophs and phototrophs, as well as other chemotrophs nutrients protiens amino acids polysaccharides monosaccharides lipids glycerol fatty acids vitamins minerals Thousands of complex reactions 16 Chemical reactions Catalyzed by enzymes Certain compartment in the CELL Thousands of complex reactions Energy Other molecules Building blocks needed in the body To be alive How can the reactions happen? 17 In a reversible reaction, what will decide the direction of the reaction ? A + B C Cell, isothermal 18 Basic concepts Free energy (G) A thermodynamic quantity, whose change at constant pressure is indicative of the spontaneity of a process. Free-energy change (ΔG) The amount of free energy released (negative ΔG) or absorbed (positive ΔG) in a reaction at constant temperature and pressure. 19 The energy that cells can and must use is FREE ENERGY, Living organisms require a continual input of FREE ENERGY 20 Q What does △G mean? A △G will determine whether the reaction will be spontaneous at constant temperature and pressure. 21 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 14.5°C to 15.5°C. 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. A kilojoule (kJ) is equal to 1000 J. 1 kcal = 4.184 kJ 22 Change in free energy (△G) during a reaction. favorable process A can be spontaneously converted into B unfavorable process B cannot be spontaneously converted into A 23 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. 24 Q How is the free energy inputted to drive a reaction with positive △ G? A A thermodynamically unfavorable reaction can be COUPLED by a thermodynamically favorable reaction. 25 Favorable and unfavorable processes could be coupled 26 Energy coupling in mechanical and chemical processes 27 the chemical intermediate B, common to both reactions, couples the reactions. 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. 28 A thermodynamically unfavorable reaction can be DRIVEN by a thermodynamically favorable reaction to which it is coupled. as long as overall △G is negative. 29 Q HOW does the cell use FREE ENERGY? A The cell uses ATP and other energy-carrier compounds , transformed from FREE ENERGY. Both chemotrophy and phototrophy (as well as autotrophy) transform the free energy into ATP and other energy-carrier compounds. 30 The First Law of Thermodynamics The energy can be neither created nor destroyed. The amount of energy in the universe is constant. The energy can be converted from one form into another. 31 ATP Basic concepts Adenosine triphosphate, ATP Adenosine diphosphate, ADP Adenosine monophosphate, AMP 32 ATP is an energy-rich molecule because its triphosphate unit contains two phosphoanhydride bonds. phosphate group transfer potential phosphoanhydride bonds, high-energy phosphate bonds 33 A large amount of free energy is liberated when ATP is hydrolyzed to ADP + Pi or AMP + PPi exergonic 34 ATP-ADP cycle a fundamental model of energy exchange in biological system Motion, active transport, signal amplification, and biosynthesis can occur only if ATP is continually regenerated from ADP. 35 Q There are two ways to form ATP. A •Substrate Level Phosphorylation •Oxidative Phoshorylation 36 Q Is ATP the only energy-carrier compound ? A There are some phosphorylated compounds ranking to energy-carrier compounds, like……. (filled it by youself) 37 Basic concepts Phosphate group transfer potential The tendency of a phosphorylated molecule to undergo hydrolysis During its hydrolysis, energy is released. The phosphoryl transfer potential is an important form of cellular energy transformation. 38 ATP is not the only compound with a higy phosphoryl transfer potential. other energy-carrier compounds Glycolysis intermediate 39 Q Why is ATP the most important energycarrier compound ? A ATP is highly accessible for energyrequiring processes, called energy currency. 40 Some compounds have a higher phosphoryl transfer potential than that of ATP and can be used to phosphorylate ADP to form ATP. 41 42 It is significant that ATP has a phosphate group transfer potential that is intermediate among the biologically important phosphorylated molecules. This intermediate position enables ATP to function efficiently as a carrier of phosphoryl groups. 43 The amount of ATP in muscle suffices to sustain contractile activity for less than a second. 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 more efficiently , Importance of ATP during exercise more rapidly The ATP must be regenerated by metabolic pathways. 44 Q HOW is the free energy transformed into ATP and other energy-carrier compounds A The free energy is transformed into ATP and energy-carrier compounds through metabolism of nutrient molecules. 45 Q HOW do we get building blocks of macromolecules for our body? A The build blocks is derived from metabolism of nutrient molecules. 46 pathway Basic concepts is formed by the coupling of enzyme-catalyzed reactions such that the overall free energy of the pathway is negative. The product of one reaction is the substrate of subsequent reaction. Specific pathways constructed from individual reactions must satisfy minimally two criteria: • • enzyme the individual reactions must be specific. the entire set of reactions that constitute the pathway must be thermodynamically favored. 47 overall △G is negative Basic concepts catabolic pathways 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. 48 Basic concepts anabolic pathways 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. Anabolic reactions often involve chemical reduction. 49 Most catabolic pathways involve the oxidation of organic molecules coupled to the generation of both energy (ATP) and reducing power (NADH). 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 50 NADP and NAD coenzyme NAD, without -PO4251 52 Energy relationships between catabolic and anabolic pathways 53 Basic concepts Metabolism different pathways intersect, forming an integrated and purposeful network of chemical reactions 54 55 56 Thousands of metabolic reactions can be subdivided into just six types. 57 Q Where do we get nutrients? A We obtain carbohydrates, lipids , proteins, main energy-providing compounds, and other nutrients from foodstuff. 58 Carbohydrates lipids proteins 59 Q What is the general process to extract energy from foodstuffs? A There are three stages in catabolism. 60 Large molecules in food are broken down into smaller units. No useful energy is captured in this phase. 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. Cell 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 61 Main topics in the Part III 62 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 63 ATP is highly accessible for energy-requiring processes, called energy currency. The free energy is transformed into ATP and energycarrier 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. 64 Summarize Q & A by yourself 65