biochemistry生物化學西文chapter1-2foundations-lecture notes for sept11,2012by professor zengyi chang

1、Biochemistry, the courseFrom Sept. 11, 2012 to Jan. 3, 2013Prof. Zengyi Chang (昌增益), Ph.D. Prof. Yongmei Qin (秦詠梅), Ph.D. The whole-classlecturersAll the teachers秦詠梅魏文勝付新苗陳浩東伊成器徐冬一田哲賢夏斌昌增益方敏謝燦金長文The graduate-student teaching assistants for the whole-class lecturing劉佳峰 (the head) 余家鈺 張媛媛 肖光輝 秦蕭 There

2、 are 10 additionalundergraduate-studentteaching assistants for the discussion classes.The textbook we use:A classic in Biochemistry since 19703rd edition (2000)5th edition (2008)4th edition (2004)2nd edition (1993)1st edition (1982)Albert L. LehningerHe has been studying bioenergeticsMember of US Ac

3、ademy of Sciences (elected in 1956)Another classic written by Lubert StryerSince 19757th edition, 2010(Born March 2, 1938, in Tianjin, China) He has been studying the interplay of light and life (vision signaling)Member of the National Academy of Sciences, USA (elected 1984) Books on the history of

4、Biochemistry:1. 昌增益（譯者）蛋白質(zhì)、酶和基因：化學與生物 學的交互作用，清華大學出版社，2005年1月。 Fruton, J. S. (1999). Proteins, Enzymes, Genes: The Interplay of Chemistry and Biology. New Heaven and London: Yale University Press. （electronic version of this book is available in the library of Peking University).2. 昌增益（譯者） 二十世紀生物學的分子

5、革命：分子生物學所走過的路，科學出版社，2002年2月。Michel Morange (2000) A history of Molecular Biology, Harvard University Press.History books onBiochemistry.Prof. Zengyi Chang have translated these two booksinto Chinese!Dr. Michel Morange in Shanghai (2009)attending the Education & HistorySession of the 21st IUBMB Congr

6、essTopic 1 the prebiotic Origin of LifeStanley L. Miller.(1953) “A Production of Amino Acids Under Possible Primitive Earth Conditions”, Science, 117:528-9.Topic 2 Protein structure determinationM.F.PERUTZ, et.al. (1960) “Structure of Haemoglobin-A Three-Dimensional Fourier Synthesis at 5.5A Resolut

7、ion, Obtained By X-Ray Analysis”, Nature, 185:416-22.Topic 3 Enzyme catalysisScoTr J. POLLACK, JEFFREY W. JACOBS, PETER G. SCHULTZ (1986), “Selective Chemical Catalysis by an Antibody”, Science, 234:1570-3.Topic 4 Nucleic acid structureWatson, J and Crick F. (1953) “Molecular Structure of Nucleic Ac

8、ids-A Structure for Deoxyribose Nucleic Acid”, Nature, 171:737-8.The eight classic papers (to be read by all students)Topic 5 Bioenergetics and catabolismPAUL D. BOYER, RICHARD L. CROSS, AND WILLIAM MOMSEN (1973) “A New Concept for Energy Coupling in Oxidative Phosphorylation Based on a Molecular Ex

9、planation of the Oxygen Exchange Reactions”, Proc. Nat. Acad. Sci. USA, 70: 2837-2839.Topic 6 AnabolismKONRAD BLOCH AND D. RITTENBERG (1942) “ON THE UTILIZATION OF ACETIC ACID FOR CHOLESTEROL FORMATION” ,J. Biol. Chem., 145:625-636.Topic 7 Regulation of metabolismH. KACSER and J. A. BURNS (1995) “Th

10、e Control of Flux”, Biochem. Soc. Trans. 23, 341366 (1995) (republished from a paper published in 1973.)Topic 8 Molecular evolutionP. J. McLaughlin and M. O. Dayhoff, (1973) “Eukaryote Evolution A View Based on Cytochrome c Sequence Data”, J. Mol. Evol., 2: 99-116.Grading policy for Biochemistry Who

11、le-class lecturing: 50%Small-class discussion: 50%Absence of class: -2 Points for each missing class (deduced from the final score)Grading policy for Biochemistry Whole-class lecturing:Tests (one at each whole-class lecture): 10%Mid-term exam: 30%.Final Exam: 60%Grading policy for Biochemistry Small

12、-class discussion:Oral presentation (in English): 30%Participation of discussion: 70%Requirements for the small-class discussion -Critical thinking -Active participation-Effective communicate skillsTo be able to read what is not written and to hear what is not said.Chapters 1-2 The realm of Biochemi

13、stryProfessor Zengyi Chang (昌增益 教授） Room 204, New Life Science BuildingTel. 6275-8822Sept. 11, 2012 The outlineWhat is life?Missions of biochemistryThe eleven themes of biochemistryProfessional organizations and journals What is life?Various forms of life: What are their common and distinguishing fe

14、atures? How are they related to each other (evolution)? Early understanding of life: VitalismLiving organisms contain some non-physical element (e.g., “spirit”) and are governed by different principles than are inanimate things. There is a vital force present only in organic, but not in inorganic ma

15、terials, the former can not be synthesized form the latter.Life can not be simply considered as machines, interaction (“force”) between components is essential for life organization (Ernst Mayr, 2002).Pasteur(1822-1895)Galen(AD 129c. 200) Mayr(1904-2005)Berzelius (17791848) Exploring life with Chemi

16、strySynthesis of urea from inorganic components (Friedrich Wohler, 1828) . (“If not the compounds, at least the reactions of living matter could occur only in living cells”)Cell-free fermentation (Edward Buchner, 1898). (“But the nature of biological catalysts are far too complex to be described in

17、chemical terms”)Enzymes, “catalysts of life”, crystallized and found to be proteins (J. Sumner, 1926 ).DNA found to be the carrier of genetic information (Oswald Avery, 1943).F. Wohler（1800-1882）E. Buchner(1860-1917)J. Sumner(1887-1955)O. Avery(1877-1955)Life: A process or conditionbut a definition

18、not yet achieved.Possessing the following basic features: Homeostasis;Organization;Metabolism;Growth;Adaptation;Response to stimuli;Reproduction.What is life?Everyone knows what life is but there is no simple definition.Scientists in the 17th century had the same problem trying to define water! A ph

19、ysicists view on lifeAn open or continuous systems able to decrease their internal entropy at the expense of substances or free energy taken in from the environment (i.e., function on negative entropy) , “avoids the decay into equilibrium”, and subsequently rejected in a degraded form. Erwin Schrodi

20、nger(1887-1961) What is life?A biochemists view on lifeProgram: an organized plan (implemented by the DNA) for the ingredients (proteins, nucleic acids, etc) and the kinetics of their interactions.Improvisation: mutation plus selection for the program to be optimized for the new environmental challe

21、nges.Compartmentalization: maintain concentration and arrangement (ensure the proper reaction kinetics; to provide protection from the outside).Energy: To compensate for the entropy gain and movements occurring.Regeneration: compensation for the losses of chemicals; diffusion and active transport of

22、 chemicals into living organisms; constant re-synthesis of constituents (e.g., heart proteins); aging and starting over of cells and individuals after death.Adaptability: feedback and feedforward reajustments; the behavioral responses being part of the Program.Seclusion: To avoid undesired contacts

23、and interference of biochemical processes; via the specificity of enzymes and specific nucleic acid interactions. The goddess of Life: PICERASD. Koshland(1920-2007)What is life?Missions of biochemistrySeeks to describe the structure, function, interaction and chemical transformation of life molecule

24、s, as well as the energetics involved in living organisms. Biochemistry explores life at the molecular level!Biochemistry is interdisciplinaryChemical foundations: Life is made around carbon (Structure and reaction).Physical foundations: Energy transformation, as explored using the terms of thermody

25、namics, occurs in life process.Mathematical foundations: The quantitative description of life processes.Computational foundations: Simulation of the biomolecules and bioprocesses; Analysis and storage of the huge amount of biochemical data.Many chemists, physicists, mathematician and computer scient

26、istsare joining the community of studying the life phenomena at the molecular level!Biochemistry draws its major themes from other life science fieldsOrganic chemistry: Properties of biomolecules.Biophysics: Applies techniques and theories of physics to study the life processes.Medical research: Dis

27、ease states in molecular terms.Nutrition: Dietary requirements for maintenance of health,Microbiology: Single-celled organisms and viruses have been used to understand life at the molecular level.Physiology: Tissue and organ functions at the molecular level.Cell biology: Biochemical division of labo

28、r within a cellGenetics: Nature of heredity at the molecular level.Biochemistry nourishes them in return and is actually penetrating all disciplines of life sciences and fuel their growth! Three principle areas of Biochemical studies1. The structural chemistry of the components of living matter and

29、the relationship of biological function to chemical structure.2. Metabolism - the totality of chemical reactions and energy transformation that occur in living matter.3. The chemistry of processes and substances that store, transmit and express biological information.Biochemistry, cell biology, and

30、genetics became inextricably interwoven! Biochemistry has contributed greatly to the improvement of human health: Nutrition & disease treatments.LeukemiaAIDSHeart block異丙基去甲腎上腺素、或 喘息定 疊氮胸苷,齊多夫定 (Zidovudine)立妥威 （Retrovir) 6-巰基嘌呤，樂疾疾寧 AZTThe eleven themes of modern biochemistry1. Purification and anal

31、ysis2. Structure and property3. Function and mechanism4. Chemical transformation5. Catalysis6. Regulation7. Information8. Interaction9. Transport and translocation10. Energy11. Evolution Theme 1: Purification and analysisComponents have to be isolated and purified before physical and chemical analys

32、is and characterization can be performed.1926, The Svedberg: ultracentrifugation.1948, Arne Tiselius: electrophoresis (of serum proteins).1952, Archer J. P. Martin, Richard L. M. Synge: partition chromatography.M. Tsvet(1872-1919) Tiselius(1902-1971) Martin(1910-2002) Synge(1914-1994) Svedberg(1884-

33、1971)Theme 2: Structure and propertyCovalent and non-covalent structures, and properties of biomolecules. Methods for analyzing the structure and property of molecules: Spectroscopy, electrophoresis, chromatography, X-ray diffraction, NMR, Mass spectrometry, atomic force and cryo- electronmicroscopy

34、, etc.Theme 2: Structure and property1902, Emil Fischer: chemical syntheses of sugar and purine.1910, Albrecht Kossel: cell chemistry made through work on proteins, including the nucleic substances.1915, Richard Willstatter: plant pigments.1923, Frederick G. Banting and John Macleod: insulin.1927, H

35、eirich Wieland: bile acids. E. Fischer(1852-1919) Willsttter(1872-1942) Wieland1877-1857) Theme 2: Structure and property1928, Adolf Windaus: sterols.1930, Hans Fischer: haemin and chlorophyll.1937, Norman Haworth: carbohydrates and vitamin C; Paul Karrer: carotenoids, flavins and vitamins A and B2.

36、Windaus(1876-1959)H. Fischer(1881-1945) Haworth(1883-1950) Karrer1889-1971) Theme 2: Structure and property1939. Adolf Butenandt: sex hormones; Leopold Ruzicka: terpenes.1943, Henric Dam, Edward A. Doisy: vitamin K.1950, Edward C. Kendall, Tadeus Reichstein, Philip S. Hench: hormones of the adrenal

37、cortex.1954, Linus Pauling: structure of complex substances (i.e., proteins).Butenandt1903-1995) Doisy1893-1986) Dam(1895-1976) Hench(1896-1965)Kendall(1886-1972) Reichstein(1897-1996) PaulingTheme 2: Structure and property1957, Lord Todd: nucleotides and nucleotide co-enzymes.1958, Frederick Sanger

38、: structure of proteins (insulin sequence).1962, Max F. Perutz and John C. Kendrew: structures of globular proteins.1962, Francis Crick, James Watson, Maurice Wilkins: molecular structure of nucleic acids.1964, Dorothy Crowfoot Hodgkin: structures of important biochemical substances (penicillin).197

39、0, Luis Leloir: sugar nucleotides.ToddPerutz(1914-2002)KendrewHodgkin(1910-1994)Leloir(1906-1987)SangerWatson & CrickTheme 2: Structure and property1972, Gerald M. Edelman, Rodney R. Porter: chemical structure of antibodies.1977, Roger Guillemin, Andrew V. Schally, Rosalyn Yalow: peptide hormones.19

40、78, Werner Arber, Daniel Nahans, Hamilton O. Smith: restriction enzymes.1982, Sune K. Bergstrom, Bengt, I. Samuelsson, John R. Vane: prostaglandins.Porter(1917-1985)Porter(1929-)Bergstrm GuilleminTheme 2: Structure and property1989, Sidney Altman, Thomas E. Cech: catalytic properties of RNA.1998, Ro

41、bert F. Furchgott, Louis J. Ignarro, Ferid Murad: nitric oxide.2006，Roger D. Kornberg: molecular basis of eukaryotic transcription (RNA Polymerase II).2009, Venkatraman Ramakrishnan, Thomas A. Steitz, Ada E. Yonath: structure and function of the ribosome.FurchgottRamakrishnanKornbergThe making of th

42、e life molecules much depend on the availability of carbon and water on the earth.The versatile bonding properties of carbon probably enabled its selection to organize the chemistry of lifeIt accounts for more than half of the dry weight of all cells.It is able to link into linear or branched chains

43、 and cyclic structures, to which all kinds of functional groups (e.g., alcohol, amino, carboxyl) can be attached.It makes the skeleton for proteins, nucleic acids, carbohydrates, lipids and other important biomolecules.Diamond (the hardest)Graphite (one of the softest)10 million carbon compounds are

44、 found! The three-dimensional nature of carbon compounds allow biomolecules to recognize each other in stereospecific precision.The four single bonds around a carbon have a characteristic tetrahedral arrangement (1875):Life is three-dimensional.Carbon-carbon single bonds: Free to rotate.Carbon-carbo

45、n double bonds:The two carbons and atoms attached to them all lie in the same rigid (non-rotatable) plane.J. H. van t Hoff(1852-1911)J. A. Le Bel(18471930) The 3-D structure of carbon compounds is a combination of configuration and conformationConfiguration (構型) defines the different spatial arrange

46、ments in covalent bond linkages to carbons that are chiral or form double bonds (unable to be interconverted without breaking covalent bonds). Conformation （構象）defines the different spatial arrangements of atoms due to the rotational C-C bonds (all having the same covalent linkages; countless for sm

47、all molecules but usually unique for large ones). A cis to trans configurational change of 11-cis retinal is a key event in visual signaling.George Wald(1967 Nobel Prize) Photoisomerization A GPCRmembraneproteinThe two are enantiomersThe two are the same The presence of an asymmetric carbon also gen

48、erates two configurational isomers designated as enantiomers (對映體) one tothe other.Asymmetric carbon(chiral center)Enantiomers: stereoisomers that are mirror images of each other but are non-superposable (not identical)Discovered by Louis Pasteur in 1848, demonstrate almost identical chemical and ph

49、ysical properties, except in optical activity: rotating the plane of plane-polarized light in opposite directions with the same degree.An equal molar mixture of two enantionmers, i.e., a racemic mixture, shows no such optical activity.In living organisms, commonly only one of the two enantiomers is

50、produced and used (e.g., L-amino acids, D-glucose, etc).Jns Jacob Berzelius (1779-1848)Introduced the conceptof isomerismEnantionmers may exhibit dramatically different physiological effects: to be sweet or bitter! Non-saccharide sweetenerPhenylketonuria (PKU) patient should avoid it. AminoSweet 200

51、 times sweeter than sucrose Water as the medium of life: The unique thermal and solvent propertiesWater is a polar molecule, forming H-bonds between themselves (thus highly cohesive and commonly exist as liquid ) or with other molecules.Water greatly weakens electrostatic forces and hydrogen bonding

52、 between polar molecules, thus being an excellent solvent for polar molecules.Life undoubted could not have arisen in the absence of water!北大水科學復合型拔尖人才培養(yǎng)計劃Thermal properties of water: high boiling point, high melting point, high heat of vaporization and high heat capacity (good thermal buffer). A li

53、quid at room temperature.Each water canForm H-bondwith 4 otherwater moleculesHydrogen bonding between water molecules generates hydrophobic interaction between hydrophobic molecules, which in turndrive the formation ofbiomembranes.Water forces amphipathic molecules to spontaneously rearrange themsel

54、ves to form uniquestructures.Life on earth has been evolved in waterNearly all biomolecules assume their shapes (and therefore their functions) in response to the physical and chemical properties of the surrounding water, thus proteins fold into their native conformations and lipid bilayers are form

55、ed and maintained).Water is the medium for the majority of biochemical reactions.Water actively participate in many chemical reactions supporting life.Oxidation of water (producing O2) is fundamental to photosynthesis.Theme 3: Function and mechanismThe role (function) of a biomolecule in a living or

56、ganism, as well as its action mechanism have to be explored.1923, Frederick G. Bantiing and John Macleod: insulin.1931, Otto Warburg: nature and mode of action of the respiratory enzyme.1947, Bernardo Houssay: hormone of the anterior pituitary lobe in the metabolism of sugar.1955, Hugo Theorell: nat

57、ure and mode of action of oxidation enzymes.1962, Max F. Perutz and John C. Kendrew: structures of globular proteins.Theme 3: Function and mechanism1972, Christian Anfinsen: amino acid sequence and the biologically active conformation; Stanford Moore and William H. Stein: catalytic activity of the a

58、ctive centre of the ribonuclease.1975, John Corforth: stereochemistry of enzyme-catalyzed reactions.1977, Roger Guillemin, Andrew V. Schally, Rosalyn Yalow: peptide hormones.1978, Werner Arber, Daniel Nahans, Hamilton O. Smith: restriction enzymes.Theme 3: Function and mechanism1986, Stanley Cohn, R

59、ita Levi-Montalcini: growth factors.1989, Sidney Altman, Thomas E. Cech: catalytic properties of RNA.1991, Erwin Neher, Bert Sakmann: single ion channels.1994, Alfred G. Gilman, Martin Rodbell: G-proteins.1997, Stanley B. Prusiner: Prions.1997,Jens C. Skou: ion-transporting enzyme.Theme 3: Function

60、and mechanism1988, Johann Deisenhofer, Robert Huber, Hartmut Michel: photosynthetic reaction center.1997, Paul D. Boyer, John E .Walker: synthesis of ATP.2001, Leland H. Hartwell, Tim Hunt, Sir Paul Nurse: regulators of the cell cycle.2002, Sydney Brenner, H. Robert Horvitz, John E. Sulston: regulat