Instructors for Biochemistry

1. Instructors for Biochemistry Downloaded from www.pharmacy123.blogfa.com

2. Biochemistry IIMetabolism:The totality of the transformation of biomolecules (matter) and energy Downloaded from www.pharmacy123.blogfa.com

3. Definition of Metabolism • The entire highly integrated and regulated network of chemical transformations (as stepwise metabolic pathwayscatalyzed by many enzymes) occurring in a living organism (through which cells extract energy and reducing power from its environment, as well as synthesize the building blocks of its macromolecules and then the macromolecules themselves). Downloaded from www.pharmacy123.blogfa.com

4. Coenzymes (vitamines) Amino acids carbohydrate hormones nucleotides Amino acids lipids Downloaded from www.pharmacy123.blogfa.com 22nd edition designed by Dr. Donald E. Nicholson

5. For maps of metabolic pathways see:http://www.iubmb-nicholson.org/ Downloaded from www.pharmacy123.blogfa.com

6. metabolism is categorized into two types • Catabolism (biodegradation): larger molecules (nutrients and cell constituents) are broken down (often via exergonic reactions) to salvage (reuse) their components or/and to generate energy. • Anabolism (biosynthesis): The generation of biomolecules from simpler components (often via endergonic reactions). The Ying & Yang of Metabolism Downloaded from www.pharmacy123.blogfa.com

7. (Fuels) The Ying & Yang of Metabolism Exergonic Oxidation Biodegradation Output of energy Simpler Metabolites Complex Metabolites Input of energy Endergonic Reduction Biosynthesis Downloaded from www.pharmacy123.blogfa.com

8. Major Roles of Metabolism • Extract energy and reducing power from the environment (photosynthesis and oxidative degradation of nutrients). • Generation (interconversion) of all the biomolecules for a living organism. Thus comes the term “Dynamic Biochemistry” Downloaded from www.pharmacy123.blogfa.com

9. (Fuels) The role of Metabolism Extract energy and reducing power ATP: Energy currency Also for mobility, transport of nutrients and so on. Generate all biomolecules Downloaded from www.pharmacy123.blogfa.com

10. Classification of organisms based on trophic (“feed”) strategies • Autotrophs—synthesize all cellular components from simple inorganic molecules (e.g, H2O, CO2, NH3, H2S). • Heterotrophs—Derive energy from oxidation of organic compounds (made by autotrophs). Downloaded from www.pharmacy123.blogfa.com

11. Metabolism in various living organisms allow carbon, oxygen and nitrogen to be cycled in the biosphere.The cycling of matter is driven by the flow of energy in one direction through the biosphere! Downloaded from www.pharmacy123.blogfa.com

12. Metabolism allows the cycling of C/O and the flow of energy in the biosphere glucose Producers Consumers H2O Downloaded from www.pharmacy123.blogfa.com

13. Metabolism also allows the cycling of N in the biosphere (NH4+) NO3- NO2- Downloaded from www.pharmacy123.blogfa.com

14. General Features of Metabolism • Occurs in specific cellular (tissue and organ) locations as a series of enzyme-catalyzed linear, branched or circular reactions, or pathways. • Highly coupled and interconnected (“Every road leads to Rome”). • Highly regulated(often reciprocally) to achieve the best economy (“Balanced supply and demand”). • The number of reactions is large (over 1000), however, the number of types of reactions is relatively small (what happens in animal respiration happens in plant photosynthesis). • Well conservedduring evolution: reflecting the unity of the life phenomena (“what happens in bacteria happens in human being”). Downloaded from www.pharmacy123.blogfa.com

15. (乙酰辅酶A) Downloaded from www.pharmacy123.blogfa.com

16. General approaches for studying metabolism • Purification and Chemical characterization of metabolites; • Tracing the fates of certain biomolecules in living subjects (via such chemical labels as isotopes). • Isolation of genetic mutants having genetic defects. • Identification and characterization of enzymes. Downloaded from www.pharmacy123.blogfa.com

17. Issues for current and future investigation on metabolism • Continue to unveil new pathways and new regulation strategies of metabolism. • Studies on enzymes. • Observation of metabolic processes in intact living organisms (e.g., in the brains under various states) • Metabolism differences among various organisms or various states of the same organism (for diagnosing and treating such diseases as cancer, infections of bacteria or viruses, obesity, etc; to understand aging). • Appropriate and inappropriate nutrition. • Biotechnological application of knowledge learned from metabolic studies in medicine, agriculture and industry. Downloaded from www.pharmacy123.blogfa.com

18. Nobel Prizes in revealing the Metabolism of living matter (1) • 1907, Eduard Buchner: cell-free fermentation. • 1922, Archibald B. Hill: production of heat in the muscle?; Otto Meyerhof: fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle. • 1923, Frederick Grant Banting, John James Richard Macleod: discovery of insulin. • 1929, Arthur Harden, Hand von Euler-Chelpin: fermentation of sugar and fermentative enzymes. • 1929, Christiaan Eijkman: antineuritic vitamin; Sir Frederick Gowland Hopkins: growth-stimulating vitamins. • 1931, Otto Heinrich Warburg: nature and mode of action of the respiratory enzyme. Downloaded from www.pharmacy123.blogfa.com

19. Nobel Prizes in revealing the Metabolism of living matter (2) • 1934, George Hoyt Whipple, George Richards Minot, William Parry Murphy: liver therapy in cases of anaemia. • 1937, Albert Szent-Gyorgyi: biological combustion, vitamin C and the catalysis of fumaric acid. • 1943, Henrik Carl Peter Dam: discovery of vitamin K; Edward Adelbert Doisy: chemical nature of vitamin K. • 1947, Carl Cori and Gerty Cori: catalytic conversion of glycogen; Bernardo Houssay: hormone of the anterior pituitary lobe in the metabolism of sugar. • 1950, Edward Calvin Kendall, Tadeus Reichstein,Philip Showalter Hench: hormones of the adrenal cortex, their structure and biological effects. • 1953, Hans Krebs: citric acid cycle; Fritz Lipmann: role of co-enzyme A in metabolism. • 1955, Axel Hugo Theodor Theorell: nature and mode of action of oxidation enzymes“. Downloaded from www.pharmacy123.blogfa.com

20. Nobel Prizes in revealing the Metabolism of living matter (3) • 1961, Melvin Calvin: carbon dioxide assimilation in plants. • 1964, Konrad Bloch, Feodor Lynen: cholesterol and fatty acid metabolism. • 1971, Earl W. Sutherland, Jr.: mechanisms of the action of hormones. • 1978, Peter Mitchell: chemiosmotic theory of biological energy transfer. • 1982, Sune K. Bergström, Bengt I. Samuelsson, John R. Vane: prostaglandins and related biologically active substances. • 1985. Michael S. Brown, Joseph L. Goldstein: regulation of cholesterol metabolism. Downloaded from www.pharmacy123.blogfa.com

21. Nobel Prizes in revealing the Metabolism of living matter (4) • 1988, Sir James W. Black, Gertrude B. Elion, George H. Hitchings: principles for drug treatment. • 1988, Johann Deisenhofer, Robert Huber, Hartmut Michel: photosynthetic reaction centre. • 1992, Edmond H. FischerEdwin G. Krebs: reversible protein phosphorylation as a biological regulatory mechanism. • 1994, Alfred G. GilmanMartin Rodbell: G-proteins and the role of these proteins in signal transduction in cells. • 1997, Paul D. Boyer, John E .Walker: synthesis of ATP. • 1998, Robert F. Furchgott, Louis J. Ignarro, Ferid Murad: nitric oxide as a signalling molecule in the cardiovascular system. Downloaded from www.pharmacy123.blogfa.com

22. Nobel Prizes in revealing the Metabolism of living matter (5) • 1999, Gunter Blobel: protein localization. • 2000, Arvid Carlsson, Paul Greengard, Eric R. Kandel: signal transduction in the nervous system. • 2001, Leland H. Hartwell, Tim Hunt, Sir Paul Nurse: regulators of the cell cycle. • 2002, Sydney Brenner, H. Robert Horvitz, John E. Sulston: regulation of organ development and programmed cell death. • 2004, Aaron Ciechanover, Avram Hershko, Irwin Rose: ubiquitin-mediated protein degradation. Downloaded from www.pharmacy123.blogfa.com

23. Major aspects that will be covered in Biochemistry II • General principles for bioenergetics. • Oxidative degradation of fuels (glycolysis, b- oxidation, a-ketoacid oxidation, citric acid cycle), generating NADH, FADH2, ATP, and CO2. • Oxidation of NADH and FADH2 by O2 and generation of ATP and H2O (respiratory chains, ATP synthase). • Biosynthesis of carbohydrates (including photosynthsis), fatty acids, amino acids, and nucleotides. • Metabolites, chemical reactions, enzymes, regulations, with wide applications in medicine, agriculture, and biotechnology. Downloaded from www.pharmacy123.blogfa.com

24. How to study metabolism • Compare and relate (interconnect) the chemical reactions (Where are you in the metabolism network?) • Try to contemplate on the ways the living organisms used to achieve a balanced and dynamic steady state (How could the multilayered regulation cooperate so effectively?). • Understand the classical experiments and thoughts that led to the revelation of the knowledge described (Does He/she deserve the Nobel Prize?). • Be aware of the nature of the data (Could this observations from in vitro studies be extended to what happens in vivo?). • Understand the aspects that need further studies (Do I still have a chance to win a Nobel Prize?). Downloaded from www.pharmacy123.blogfa.com

25. Enjoy Biochemistry II: a course that will allow you to learn what life is really all about. Downloaded from www.pharmacy123.blogfa.com

26. Scoring policies for this course • Tests (attendance): 10%; • Critical reading of a research paper (one paper for each two students): 15%; • Final Exam: 75%. Downloaded from www.pharmacy123.blogfa.com

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