Entre the Microcosmos of Life

Introduntion to

Biochemistry
Youquan Bu Ph.D.
Department of Biochemistry and Molecular Biology, Chongqing Medical University

The big bang

Elementary particle

Atom

Basic small molecules

Biomacromolecues

Larger small molecules

 Human body cell molecules

 Example: Molecules and Diseases Exploration on the casue of Sickle Cell Anemia
High incidence rate in Africans, described in Tribes
1910, U.S. Chicago, James Herrick and Ernest Irons

found the sickle shaped cells in one patient 1947, Michigan University, James V. Neel recognize it as genetic disease

James Herrick

Sickle shaped cells

 1951, Linus Pauling and Harvey Itano found the

abnormal structure of Hb-S, propose the concept of molecular disease. 1956, Vernon Ingram found the AA mutation in Hb-S 1970sfound the genetic mutation in Hb gene
N-terminal AA seq. of Hb- 1
Hb-Anormal Hb-Spatient

Val-His-Leu-Thr-Pro-Glu-Glu-Lys Val-His-Leu-Thr-Pro-Val-Glu-Lys

GAA (Glu) GTA (Val) Normal cell Sickle-cell

 The elucidation of its molecular mechanism led

to the application of gene diagnosis and gene therapy for sickle cell anemia.

Biochemistry in daily life

Mad cow disease? Trans fatty acids are harmful? Weight reduction in good way? fasting of 49 days possible? Nucleic acids or genes are nutrient substances? The common sense of Drink wine/liquor Cigarette,environmental pollution cause cancer? .

 Excessive intake of sweet foods causes obesity?

glucose

Conversion of sugar to fat

G-6-P

Glyceral

Fat Fatty acids

Pyruvate
Acetyle-CoA

TCA cycle

CO2 ATP H2O

Compared with normal miceLeptin knockout mice (Ob/ob mouse) is much more fater

The left is Ob/ob mouse and the right is the normal mouse

Introduction to Biochemistry
What

is biochemistry?

Brief

history of Biochemistry
of Biochemistry

Contents

Biochemistry
Teaching

and medical science

arrangements

1. What is biochemistry?
Biochemistry: The chemistry of life

Biochemistry is the application of chemistry to the study of biological processes at the cellular and molecular level. Biochemistry can also be described as the science concerned with the chemical constituents of living cells and with the reactions and processes they undergo.

 The major objective of biochemistry is the complete understanding, at the molecular level, of all of the chemical processes associated with living cells.
It emerged as a distinct discipline around the beginning of the 20th century when scientists combined chemistry, physiology and biology to investigate the chemistry of living systems.

 A Knowledge of Biochemistry Is Essential to All Life Sciences. All life on Earth depends on biochemical reactions and processes. Thus, biochemistry has broken down the old barriers among all life sciences, has become the basic language of all biologic sciences.

 Biochemistry is a young, fast developing, highly active field in natural sciences. It has deeply revolutionized the biomedical sciences In China, Biochemistry and Molecular Biology were independently separated from each other at early times, but now is a single whole discipline in biology science.

2. A Brief History of Biochemistry 2.1 Scientific Background

Prosperous Chemistry in 19th century
In 19th century, the theory and techniques of chemistry are well developed enough to be used for the research of life at molecular level, i.e. biochemistry.

Development of biomedical sciences

15th, The Renaissance, Biology began to quickly develop and grow Mid 16thAndreas Vesalius, human anatomy 17th, William Harvey, Blood circulation 17th, Antony van Leeuwenhoek', microbiology 18th, Carolus Linnaeus, taxonomy--scientific names for all his species

Vesalius

Harvey Leeuwenhoek Linnaeus

 1802, Jean-Baptiste Lamarck, the term of Biology 1830s, Schleiden and Schwann, cell theory 1859Charles Darwin, evolutionary theory 1865Gregor Mendel, genetics

In summary: Biology developed from a descriptive to a experimental discipline, from organic level to cellular and molecular levels.

Schleiden

Schwann Darwin

Mendel

2.2 The birth & development of Biochemistry

Birth of Biochemistry
A inter-discipline Its birth and development is based on the development of physics, chemistry, biology and medicine.

 1877Hoppe Seyler firstly suggest Biochemie 1903Carl Neuberg used the word of Biochemie, and then widely accepted, viewed as the father of biochemistry 1906Chief Editor of Biochemische Zeitschrift currently known asFEBS J

Carl Neuberg

FEBS the Federation of European Biochemical Societies is the Federation of the Societies of Biochemistry and Molecular Biology in more than 42 countries within the continent, 1964.

Prosperous Physics in 19th & 20th century

Lots of Physicists turned to study biology Led to the birth and development of Molecular Biology
Erwin Schrdinger (Austria) 18871961 The father of quantum physics In 1944, he wrote the famous What is Life?.

 Early period Descriptive Biochemistry Before early 20th The isolation, purification, structure, qualitative and quantitative characterization of the various chemical constitutes of organisms. Breaking down of the Louis Pasteurs Vitalism which controled the biology field for a long time. Representative figures: Edward Buchner etc

 Edward BuchnerGermany 1907, Nobel Prize for the discovery of cell-free

fermentation
Showed that the fermentation of sugars by yeast, a process that occurs when making beer, wine and bread, could be carried out with the cell extracts of yeast cell. Living cells were not required to carry out this complex series of Edward Buchner 1860--1907 reactions. Break down Vitalism.

 Emil Fischer 1902, Nobel Prize for the purine and sugar research Also contributed to protein and enzyme research

Emil Fischer 18521919

 Prosperous periodDynamic Biochemistry

Early 20th century Lots of new discoveries, basic theories of traditional biochemistry, especially enzymes and metabolic pathways.
James B. SumnerAmerican1926, isolated and crystallized the Urease. 1946, Nobel Prize for the chemical nature of enzymes. Gustav EmbdenGermanymetabolism of sugar, fat, and amino acides Hans Adolf KrebsGermany, urea cycle and identification of two important metabolic cycles: the urea cycle and the citric acid cycle. 1953, Nobel Prize.

Hans A. Krebs

19001981 A German-born British physician and biochemist. Krebs is best known for his identification of two important metabolic cycles: the urea cycle and the citric acid cycle. The citric acid cycle, the key sequence of metabolic chemical reactions that produces energy in cells, is also known as the Krebs cycle and earned him a Nobel Prize in 1953, which he shared with Fritz Lipmann.

 A milestone turningMolecular Biology

Since mid 20th The theme: nucleic acids Milestone discovery in both biology and medicine: DNA double helix
1869 Friedrich Miescher Discovered DNA

1944 1953 1958 1961

Oswald Avery,Colin Mcleod etc James Watson,Francis Crick Matthew Meselson,Franklin Stahl Francis Jacob,Sidney Brenner, Matthew Meselson 1966 Marshall Nirenberg, Har Gobind Khorana

DNA is genetic material DNA double helix DNA replication mRNA, operon theory
mRNA, genetic code

1953, Watson and Crick, DNA double helix 1962, Nobel Prize

Francis H. Crick

James D. Watson

 Biochemistry in China:

Ancient era:
Liquor makingTofu

Contemporary era:
Returned overseas from UK & US 1919-1922Hsien Wu, blood sugar determination 1924-1942Hsien Wu, Protein denaturation 1965 in vitro synthesis bovine insulin 2001HGP1%

3. The contents of Biochemistry

Structures and functions of biomacromolecues Protein, nucleic acids, enzyme etc Metabolism and its regulation Carbonhydrates, lipids, amino acids, and nucleotide metabolism Connections and regulation of metabolism Genetic information flow and its regulation Biosynthesis of DNA, RNA, and protein Gene expression and its regulation (molecular biology) Special topics biochemistry of organ/tissue/cells Hepatic biochemistry Cellular signal transduction

 Structures and functions of biomacromolecues Protein, nucleic acids, enzyme etc

 Metabolism and its regulation Carbonhydrates, lipids, amino acids, and nucleotide metabolism Connections and regulation of metabolism

 Genetic information flow and its regulation Biosynthesis of DNA, RNA, and protein Gene expression and its regulation (molecular biology)

 Special topics biochemistry of organ/tissue/cells Hepatic biochemistry Cellular signal transduction

4. Biochemistry and medicine

Biochemistry & medicine are closely related. A reciprocal relationship between Biochemistry & Medicine has stimulated mutual advances.
Advances in biochemical knowledge have illuminated many areas of medicine. Conversely, the study of diseases has often revealed previously unspected aspects of biochemistry.

 Most & perhaps all disease has a biochemical basis.

We believe that most if not all diseases are manifestations of abnormalities of molecules, chemical reactions, or biochemical processes. Biochemical approaches are often fundamental in illuminating the causes of diseases and in designing appropriate therapies. Health depends on a harmonious balance of biochemical reactions occurring in the body, and disease reflects abnormalities in biomolecules, biochemical reactions, or biochemical processes.

Typical molecular disease: sickle-cell anemia

Biochemistry and medical education

Essential required course The knowledge of biochemistry is very important for latter clinical course study. Biochemistry course for US &Japanese medical students In China, Biochemistry learning at medical colleges
Students: biology education background Teachers: academic levels Learning times: not enough

5. Teaching arrangements & learning methods

5.1 Teaching arrangements

Three parts, twelve chapters Four teachers

Introduction Parts I: structures and functions of biomacromolecues Proteins Nucleic acids Enzymes (vitamins) Biological oxidation

Carbonhydrates metabolism
Part II: metabolism and its regulation Lipid metabolism Amino acid metabolism Nucleotide metabolism Connections and regulation of metabolism Part III: genetic information flow and its regulation DNA biosynthesis RNA biosynthesis Protein biosynthesis Hepatic biochemistry Cellular signal transduction

Final review

5.2 Learning methods

Biochemistry Lots of contents; abstract; descriptive/static and dynamic Suggested methods Understanding rather than mechanically memorize; Summarize by urself Self-learning ability Aim of study Utilize knowledge of biochemistry to analyze and/or explain disease and related issues. High level study Learning biochemistry, molecular biology, genetics, and cell biology together.

6. Textbook and other resources

Biochemistry and Molecular Biology. 2007. Harper's illustrated biochemistry. 27th ed. 2006. Instant notes on Biochemistry.

Thanks for your attention!

YouQuan Bu