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 BiochemistryPrinciples of Bioche
4、mistry (3rd Edition)(3rd Edition) H.R.HortonH.R.Horton等主编，科学出版社等主编，科学出版社 2003.42003.4 生物化学（第三版）生物化学（第三版） 王镜岩、朱圣庚等主编，高等教育出王镜岩、朱圣庚等主编，高等教育出 版社版社 2002.92002.9 Contents of Biochemistry (1) -This semester Chapter 1 Introduction to Biochemistry Chapter 2 Waters Chapter 3 Amino Acids and Primary Structures
5、 of Proteins Chapter 4 Proteins: Three-Dimensional Structure and Function Chapter 5 Properties of 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
6、.2 What are the questions for biochemists to answer? 1.3 Biochemistry and other disciplines. 1.4 Application 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 centur
7、y 20. Period 3 Rapid Development PhaseFrom 1950s to present. 1780s Antoine Laurent Lavoisier (French): 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 “
8、The Phlogiston Theory” Period 1 Origin Phase Modern Biochemistry was born in the late century 18 as 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 theo
9、ry”. In 1828 ， F.Whler (Germany Chemist，1800-1882）showed by synthesizing urea from ammonium cyanate 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 founder
10、s of Biochemistry. Nutrient of food were divided into Carbohydrate, Lipid and Protein. Proteins from 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
11、transformed to urea. Brought the term “Metabolism” for the first time. Ferment was a soluble protein. 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 “pasteuri
12、sm”。 2. Every infectious disease was produced from a microorganism. Salvation French silk industry as 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
13、) can ferment sugar to alcohol. Enzyme can function when removed from the living cell. Rejected “vitalism 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 .“-os
14、e” was postfix of carbohydrates. In 1877, F.Hoppe-Seyler (Genman doctor) called the term “Physiological chemistry” for the first time. Originated “Journal of Physiological chemistry” Isolated Heme and obtained its crystal. In 1868, J F Miescher (Sweden doctor) isolated “nuclein” to be the founder of
15、 nucleic acid. In 1888, A.Kossel (German biochemist) proved “nuclein” was a complex of protein and nucleic 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 diffenen
16、t nucleic acidRNA and DNA. Founded nucleotide. But made mistakenly “Four nucleotide hypothesis”. Emil 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-Ke
17、y theory” of Enzyme. In 1903,C.A.Neuberg (German) named the term “Biochemistry”. Established the “Glycolysis 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 o
18、f purification as chromatograpy, electrophoresis, fluorescence analysis, isotope, ultracentrifuge and 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 En
19、zyme are protiens. In 1937,A.Krebs (English biochemist) discovered “Urea Cycle” and “Tricarboxylic Acid 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
20、biochemist) In 1911,C. Funk (Poland chemist):Vatamin B1,Funk named it “Vitamine”, meaning “Vital amine” . 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 discover
21、ed Secretin(促胰液素促胰液素), In 1922, F.G.Banting (Canadian physiologist) and C.H.Best purified Insulin. DNA carries 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.C
22、hase-T2 phage . Bacteria transformation 1. The colony of Wild- type Streptococcus pneumoniae is smooth (Type S).The colony of a mutant is rough (Type R).Their difference is on formation of capsule. capsule colony toxicity Type S yes smooth yes Type R no rough no Griffiths experiment Conclusion: A su
23、bstance from a dead toxic bacterium can transform into another living nontoxic bacterium. The process was called “Transformation”.The transformed substance was named “tranforming factor”. Averys experiment: Conclusion: The evidence presented supports the belief that a nucleic acid of the desoxyribos
24、e 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 Chemical Nature Of The Substance Inducing Transformation Of Pneumococcal Types Induction Of Transformation By A Desoxyribonu
25、cleic 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 biologist) and E.Tatum proved that a gene controls the synthesis of a enzyme.And they theorized “One gene one enzyme hypothesis”. P
26、eriod 3 Rapid Development PhaseFrom 1950s to present. The composition, sequence, structure and function of biological macromolecular such as protein, enzyme and nucleic acid were researched profoundly. Chemical synthesis technology was been greatly developed. Genetic engineering was established. In
27、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 Biology. In 1958, F.Crick put forward “central dogma”. In 1966, Nirenberg & Khorana decoded genetic code. R.Franklin F.Crick J.wa
28、tson 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 and J.Monod put forward “operon theory”. The inventor of DNA sequencing, double Nobel prize winner Fred Sanger In 1970, H.Temin
29、 and D.Baltimore found reverse transcriptase meantime. In 19721973, Paul Berg and Cohen etc. established DNA recombinant technology resulting in birth of “Genetic Engineering”. Basic procedure of gene cloning Basic procedure of gene cloning Target DNA fragment RE digestion Plasmid RE digestion Ligat
30、ion Recombinant plasmid Target DNA fragment Transformation E.Coli without vector die E.Coli with vector grow Culture in the medium containing antibiotic In 1975 ， E.Southern invented molecular hybridization to probe DNA”Southern Blot”. In 1982 and 1983，T.Cech and S.Altman discovered “ribozyme” respe
31、ctively. In 1985 ， K. Mullis invented “Polymerase Chain Reaction (PCR)”. Cech Altman Mullis Human Genomic Project (HGP): In 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
32、 working draft of Human gene sequence was published. In 1997，sheep Dolly-the first mammal to be cloned from an adult cell by 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 t
33、herapy ideas on patients with Thalassemia( (地中海贫血症地中海贫血症) ), but failed to help his subjects. On Sep.14,1990, W.F. Anderson completed 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.
34、On Sep.17, 1999， A 18-year-old teenager Jesse Gelsinger with ornithine transcarboxylase deficiency (OTCD) received the gene therapy. 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 f
35、irst on chemically synthesis bovine insulin in 1965 and yeast alanine transfer RNA in 1983 respectively. 1% sequencing DNA of HGP were completed by China. Gene therapy medicine p53(Gendicine,今又生今又生) was marked first in the world. 1.2 What are the questions for biochemists to answer? 1.What are the b
36、iomolecules (composition and structure)? 2.How do biomolecules act and interact? 3.How are the biomolecules synthesized (biosynthesis)? 4. How is energy generated and consumed (energy metabolism, its source and fate)? 5.How are the myriad of biochemical reactions regulated (the coordination problem,
37、 the network of control)? 6.What is the carrier of genetic information and how is it expressed and transmitted (information pathway)? 7.How do cells and organisms grow, differentiate and reproduce? 8. What is the molecular basis of evolution? 9. What makes living organisms so diversified? (advantage
38、s, 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
