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1、Biochemistry,Yongge Wu School of Life Science National Engineering Laboratory for Aids Vaccine Jilin University,What is Biochemistry ?,Biochemistry is the study of the molecules and chemical reactions of life. It is the discipline that uses the principles and language of chemistry to explain biology
2、 at the molecular level.,Course Organization,Static part :,Dynamic part :,To introduce structure and function of biomolecules (proteins, nucleic acids, carbohydrates, lipids etc.),To introduce chemical actions, courses and reactions in living systems, that is Metabolism.,Protein Enzyme Carbohydrate
3、Lipid Nucleic Acid Vitamin Hormone,Static biochemistry,Dynamic biochemistry,Metabolism and energy Carbohydrate metabolism Lipid metabolism Protein metabolism Nucleic acid metabolism Genetic information transmission,Contents of biochemistry,The Textbooks,Principles of Biochemistry (3rd Edition) H.R.H
4、orton等主编，科学出版社 2003.4 生物化学（第三版） 王镜岩、朱圣庚等主编，高等教育出版社 2002.9,Contents of Biochemistry (1) -This semester,Chapter 1 Introduction to Biochemistry Chapter 2 Waters Chapter 3 Amino Acids and Primary Structures of Proteins Chapter 4 Proteins: Three-Dimensional Structure and Function Chapter 5 Properties of
5、Enzymes Chapter 6 Mechanisms of Enzymes Chapter 7 Carbohydrates Chapter 8 Lipids and Membranes Chapter 9 Coenzymes and Vitamins,Chapter 1 Introduction to Biochemistry,1.1 Brief history of biochemistry 1.2 What are the questions for biochemists to answer? 1.3 Biochemistry and other disciplines. 1.4 A
6、pplication of biochemistry 1.5 Basic properties of living systems,1.1 Brief history of Biochemistry,Period 1 Origin Phase the late century 18.,Period 2 Developing PhaseFrom the forepart to 40s of century 20.,Period 3 Rapid Development PhaseFrom 1950s to present.,1780s Antoine Laurent Lavoisier (Fren
7、ch): Combustion of a candle is similar to the “respiration ”of animals, as both need O2 . For the first time a physiological process was explained with reference to a nonliving mechanism. Disaffirming “The Phlogiston Theory”,Period 1 Origin Phase Modern Biochemistry was born in the late century 18 a
8、s the development of Chemistry and Physiology.,In 1838, J.J.Berzelius (Sweden chemist) named the term “Protein” which was from Greek “proteios”, meaning “most important”. But he theorized “Vitalism theory”.,In 1828，F.Whler (Germany Chemist，1800-1882）showed by synthesizing urea from ammonium cyanate
9、that compounds found in living organisms could be made in the laboratory from inorganic substrances.Accordingly,he rejected the “Vitalism theory”,V.Liebig (Germany Chemist， 18031873）was one of founders of Biochemistry. Nutrient of food were divided into Carbohydrate, Lipid and Protein. Proteins from
10、 human and animal were same on structure and properties. Protein was necessary for life. Carbohydrate can been transformd to Lipid. Carbon can been transformd to CO2 by oxygenation. Nitrogen can been transformed to urea. Brought the term “Metabolism” for the first time. Ferment was a soluble protein
11、. Its function did not depend on the integrality of yeast cell.,Louis Pasteur (French microbiologist， 1822-1895) His 3 major science achievements： 1. Disaffirmed “Autogenetic theory”. Invent “pasteurism”。 2. Every infectious disease was produced from a microorganism. Salvation French silk industry a
12、s found a invasion bacterial of silkworm. 3. Invented Rabies vaccine. But he thought mistakenly that ferment can only work in living yeast cell.,1890s, E.Buchner (German): Yeast extract(no living cell) can ferment sugar to alcohol. Enzyme can function when removed from the living cell. Rejected “vit
13、alism theory”.,In 1878,W.Kuhne called them “Enzyme” for the first time. In 1883, Anselme Payen (French chemist) discover Amylase.“-ase” was postfix of enzymes. He isolated Cellulose and named it .“-ose” was postfix of carbohydrates.,In 1877, F.Hoppe-Seyler (Genman doctor) called the term “Physiologi
14、cal chemistry” for the first time. Originated “Journal of Physiological chemistry” Isolated Heme and obtained its crystal.,In 1868, JFMiescher (Sweden doctor) isolated “nuclein” to be the founder of nucleic acid. In 1888, A.Kossel (German biochemist) proved “nuclein” was a complex of protein and nuc
15、leic acid. Isolated 4 kinds of bases. Researched the structure of nucleic acid.,In 1911,P.A.T.Levine proved the structure of sugar from nucleic acid, and named it “Ribose”. Found 2 kinds of diffenent nucleic acidRNA and DNA. Founded nucleotide. But made mistakenly “Four nucleotide hypothesis”.,Emil
16、Fischer (German chemist) was one of founder of Biochemistry. In 1900s,he theoryzed “peptide bond theory” on protein structure. Invented the method of peptide synthesis. In 1894,he theorized “Lock-Key theory” of Enzyme. In 1903,C.A.Neuberg (German) named the term “Biochemistry”. Established the “Glyc
17、olysis theory”.,Period 2 Developing PhaseFrom the forepart to 40s of century 20, the chemical essence of Enzyme and biomolecular metabolism pathways were discovered with the technology improvement of purification as chromatograpy, electrophoresis, fluorescence analysis, isotope, ultracentrifuge and
18、electronic microscope.,In 1926, J. B. Sumner (American chemist): crystalliztion of urease. He proved it is a protein.,1912-1933, Biological oxidation was researched thoroughly. 1930s, proved that Enzyme are protiens. In 1937,A.Krebs (English biochemist) discovered “Urea Cycle” and “Tricarboxylic Aci
19、d Cycle” (TCA Cycle, Krebs Cycle). In 1940s, glycolysis pathway and photo-synthesis were discovered.,Discovery of Vitamin: In 1886, C.Eijkman (Netherland doctor) In 1906 Frederick Hopkins (English biochemist) In 1911,C. Funk (Poland chemist):Vatamin B1,Funk named it “Vitamine”, meaning “Vital amine”
20、 . Later it was renamed as “Vitamin”. In 1912，Hopkins and Funk put forward “vitamin deficiency hypothesis”.,Discovery of hormone: In 1902, EHStarling (English physiologist) and WMBayliss discovered Secretin(促胰液素), In 1922, F.G.Banting (Canadian physiologist) and C.H.Best purified Insulin. DNA carrie
21、s genetic information: In 1928,FGriffith (English) -the experiment of bacteria transformation. In 1944,O.T.Avery (Canada)the experiment of bacteria transformation. In 1952,A.D.Herskey and M.Chase-T2 phage .,Bacteria transformation,1. The colony of Wild-type Streptococcus pneumoniae is smooth (Type S
22、).The colony of a mutant is rough (Type R).Their difference is on formation of capsule.,Griffiths experiment,Conclusion:,A substance from a dead toxic bacterium can transform into another living nontoxic bacterium. The process was called “Transformation”.The transformed substance was named “tranform
23、ing factor”.,Averys experiment:,Conclusion:,The evidence presented supports the belief that a nucleic acid of the desoxyribose type is the fundamental unit of the transforming principle of Pneumococcus Type III. (OSWALD T. AVERY, M.D., COLIN M. MAcLEOD, M.D., AND MACLYN McCARTY,* M.D. Studies On The
24、 Chemical Nature Of The Substance Inducing Transformation Of Pneumococcal Types Induction Of Transformation By A Desoxyribonucleic Acid Fraction Isolated From Pneumococcus Type III . The Journal of Experimental Medicine. February 1, 1944,Vol. 79, No. 2, pp. 137-158),In 1946,G.Beadle (American biolog
25、ist) and E.Tatum proved that a gene controls the synthesis of a enzyme.And they theorized “One gene one enzyme hypothesis”.,Period 3 Rapid Development PhaseFrom 1950s to present. The composition, sequence, structure and function of biological macromolecular such as protein, enzyme and nucleic acid w
26、ere researched profoundly. Chemical synthesis technology was been greatly developed. Genetic engineering was established.,In 1950, Pauling put forward -Helix of protein secondary structure. In 1953, J.Watson & F.Crick established “DNA Double Helix Model”. It is the milestone of modern Molecular Biol
27、ogy. In 1958, F.Crick put forward “central dogma”. In 1966, Nirenberg & Khorana decoded genetic code.,R.Franklin,F.Crick,J.watson,M. Wilkins,In 1953 and 1975, F.Sanger won two Nobel Prizes as the invention of methods of protein sequencing and nucleic acid sequencing respectively. In 1961, F.Jacob an
28、d J.Monod put forward “operon theory”.,The inventor of DNA sequencing, double Nobel prize winner Fred Sanger,In 1970, H.Temin and D.Baltimore found reverse transcriptase meantime.,In 19721973, Paul Berg and Cohen etc. established DNA recombinant technology resulting in birth of “Genetic Engineering”
29、.,Basic procedure of gene cloning,In 1975，E.Southern invented molecular hybridization to probe DNA”Southern Blot”. In 1982 and 1983，T.Cech and S.Altman discovered “ribozyme” respectively. In 1985，K. Mullis invented “Polymerase Chain Reaction (PCR)”.,Cech,Altman,Mullis,Human Genomic Project (HGP): In
30、 1986, a Nobel prize winner R.Dulbecco published a paper in Science to first propose Human Genomic Project. In 1991,HGP began its research plan of 15 years. On June 26,2000, the working draft of Human gene sequence was published.,In 1997，sheep Dolly-the first mammal to be cloned from an adult cell b
31、y I.Wilmut.,I. Wilmut-A usurper of Gods patent.,Cloning Organ,Cloning Organism,Gene therapy: In 1980, Martin Cline from University of California at Los Angeles tested his gene therapy ideas on patients with Thalassemia(地中海贫血症), but failed to help his subjects. On Sep.14,1990, W.F. Anderson completed
32、 successfully first gene therapy on A 4-year-old girl named Ashanthi DeSilva with adenosine deaminase (ADA) gene deficiency. It was a milestone of human gene therapy. On Sep.17, 1999， A 18-year-old teenager Jesse Gelsinger with ornithine transcarboxylase deficiency (OTCD) received the gene therapy.
33、Four days later, he was dead.,Achievement of China scientists on Biochemistry: In 30s，Xian Wu put forward “Denature theory of protein”. Cooperated with several teams first on chemically synthesis bovine insulin in 1965 and yeast alanine transfer RNA in 1983 respectively. 1% sequencing DNA of HGP wer
34、e completed by China. Gene therapy medicine p53(Gendicine,今又生) was marked first in the world.,1.2 What are the questions for biochemists to answer?,What are the biomolecules (composition and structure)? How do biomolecules act and interact? How are the biomolecules synthesized (biosynthesis)?,4. How
35、 is energy generated and consumed (energy metabolism, its source and fate)? How are the myriad of biochemical reactions regulated (the coordination problem, the network of control)? 6.What is the carrier of genetic information and how is it expressed and transmitted (information pathway)? 7.How do c
36、ells and organisms grow, differentiate and reproduce?,8. What is the molecular basis of evolution? 9. What makes living organisms so diversified? (advantages, purposes and natural tendencies) 10. How do we make use of life and knowledge about life for the benefits of human being (biotechnology,bioengineering )?,Chemistry,Biology,Biochemistry,Physiology,Genetics,Auxology,Ecology,1.3 Biochemistry and other disciplines,Cell Biology,Microbiology,Medicine,Pharmacy,Chemical Biology,1.Industry: 2.Agriculture: 3.Medicine and Health: 4. ,1.4 Application of biochemistry,