Introduction to Biochemistry Department of Biochemistry Lecture 1 Introduction to Biochemistry （生物化学） Zhihong Li（李志红） Department of Biochemistry

Introduction What is the Biochemistry? History and development How to study Biochemistry?

1. Biochemistry Definition: The chemistry of life The science concerned with the chemical basis of life. The science concerned with the various molecules that occur in living cells and organisms and with their chemical reaction. Anything more than a superficial comprehension of life – in all its diverse manifestation - demands a knowledge of biochemistry.

Biochemistry Aim: to describe and explain, in molecular terms, all chemical processes of living cells Structure-function Metabolism and Regulation How life began？

Biochemistry Significance: be essential to all life sciences as the common knowledge Genetics; Cell biology; Molecular biology Physiology and Immunology Pharmacology and Pharmacy Toxicology; Pathology; Microbiology Zoology and Botany

Biochemistry Medical students who acquire a sound knowledge of biochemistry will be in a strong position to deal with two central concerns of the health sciences: (1) the understanding and maintenance of health (2) the understanding and effective treatment of disease Causes of cancers Molecular lesions causing various genetic diseases Rational design of new drugs

2. History and development of Biochemistry 1903, Neuberg (German): “Biochemistry” “Chemistry of Life”

Two notable breakthroughs (1) Discovery of the role of enzymes as catalysts (2) Identification of nucleic acids as information molecules Flow of information: from nucleic acids to proteins DNA RNA Protein

Some historic events In 1937， Krebs for the discovery of the Citric Acid Cycle-won the Nobel Prize in Physiology or Medicine in 1953 In 1953，Watson & Crick for the discovery of the “DNA Double Helix” -won the Nobel Prize in Physiology or Medicine in 1962

In 1955，Sanger for the determination of insulin sequence- won the Nobel Prize in Physiology or Medicine in 1956 In 1980， Sanger & Gilbert for Sequencing of DNA-won the Nobel Prize in Chemistry in 1980 In 1993, Kary B. Mullis for invention of PCR method -won the Nobel Prize in Chemistry in 1993

Transgenic animal Gene engineering Clone Green Fluorescence protein

HGP from 1990, completed in 2003

3.What dose the Biochemistry discuss? structure and function of cellular components proteins, carbohydrates, lipids, nucleic acids and other biomolecules Metabolism and Regulation Gene expression and modulation DNA RNA Protein

Polymers and Monomers Each of these types of molecules are polymers that are assembled from single units called monomers. Each type of macromolecule is an assemblage of a different type of monomer.

Macromolecule Carbohydrates Lipids Proteins Nucleic acids Monomer Monosaccharide Not always polymers; Hydrocarbon chains Amino acids Nucleotides

How do monomers form polymers? In condensation reactions (also called dehydration synthesis), a molecule of water is removed from two monomers as they are connected together.

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Building block Macromolecule Simple sugar Amino acid Nucleotide Anabolic Building block Simple sugar Amino acid Nucleotide Fatty acid Macromolecule Polysaccharide Protein (peptide) RNA or DNA Lipid Catabolic

Principles of Biochemistry Cells (basic structural units of living organisms) are highly organized and constant source of energy is required to maintain the ordered state. All organisms use the same type of molecules: carbohydrates, proteins, lipids & nucleic acids. Living processes contain thousands of chemical pathways. Precise regulation and integration of these pathways are required to maintain life. Instructions for growth, reproduction and developments for each organism is encoded in their DNA.

4. Cells Basic building blocks of life Smallest living unit of an organism A cell may be an entire organism (unicellular) or it may be one of billions of cells that make up the organism (multicellular). Grow, reproduce, use energy, adapt, respond to their environment Many cannot be seen with the naked eye a typical cell size is 10µm; a typical cell mass is 1 nanogram.)

Cells May be Prokaryotic or Eukaryotic Prokaryotes (Greek: pro-before; karyon-nucleus) include various bacteria lack a nucleus or membrane-bound structures called organelles Eukaryotes (Greek: eu-true; karyon-nucleus) include most other cells (plants, fungi, & animals) have a nucleus and membrane-bound organelles

•Cell membrane & cell wall •Nucleoid region contains the DNA Contain ribosomes (no membrane) • Cell Membrane • Nucleus Cytoplasm with organelles

Characteristic Bio-membranes and Organelles Plasma Membrane-Cell’s defining boundary Providing a barrier and containing transport and signaling systems. Nucleus – Cell’s information center Double membrane surrounding the chromosomes and the nucleolus. The place where almost all DNA replication and RNA synthesis occur. The nucleolus is a site for synthesis of RNA making up the ribosome Mitochondria- the power generators Mitochondria (Greek: mitos-thread; chondros-granule): Surrounded by a double membrane with a series of folds called cristae. Functions in energy production through metabolism. Contains its own DNA.

Ribosomes Protein and RNA complex responsible for protein synthesis Endoplasmic reticulum (ER) – The transport network for molecules Rough endoplasmic reticulum (RER) Covered with ribosomes (causing the "rough" appearance) which are in the process of synthesizing proteins for secretion or localization in membranes. Ribosomes Protein and RNA complex responsible for protein synthesis Smooth endoplasmic reticulum (SER) A site for synthesis and metabolism of lipids.

Golgi apparatus -process and package the macromolecules Golgi apparatus -process and package the macromolecules. A series of stacked membranes. Vesicles carry materials from the RER to the Golgi apparatus. Vesicles move between the stacks while the proteins are "processed" to a mature form. Lysosomes-contain digestive enzyme A membrane bound organelle that is responsible for degrading proteins and membranes in the cell. Cytoplasm enclosed by the plasma membrane, liquid portion called cytosol and it houses the membranous organelles.

5. Biomolecules Just like cells are building blocks of tissues, biomolecules are building blocks of cells. Animal and plant cells contain approximately 10,000 kinds of biomolecules. Water constitutes 50-95% of cells content by weight. Ions like Na+, K+ and Ca2+ may account for another 1%. Almost all other kinds of biomolecules are organic (C, H, N, O, P, S). Organic compounds are compounds composed primarily of a Carbon skeleton.

Carbon Carbon is more abundant in living organisms than it is in the rest of the universe. What makes Carbon Special? Why is Carbon so different from all the other elements on the periodic table? The answer derives from the ability of Carbon atoms to bond together to form long chains and rings.

Carbon can form immensely diverse compounds, from simple to complex. DNA with tens of Billions of Carbon atoms Methane with 1 Carbon atom

Biomolecules are compounds of carbon with a variety of functional groups Some common functional groups of biomolecules. In this figure and throughout the book, we use R to represent “any substituent.” It may be as simple as a hydrogen atom, but typically it is a carbon-containing group. When two or more substituents are shown in a molecule, we designate them R1, R2, and so forth.

Types of biomolecules Small molecules: Monomers: Polymers: Lipid, phospholipid, glycolipid, sterol, Vitamin Hormone, neurotransmitter Carbohydrate, sugar Monomers: Amino acids Nucleotides Monosaccharides Polymers: Peptides, oligopeptides, polypeptides, proteins Nucleic acids, i.e. DNA, RNA Oligosaccharides, polysaccharides (including cellulose)

Chemical composition of a normal man (weight 65 kg) Constituent Percent (%) Weight (kg) Water 61.6 40 Protein 17.0 11 Lipid 13.8 9 Carbohydrate 1.5 1 Minerals 6.1 4

Structural hierarchy in the molecular organization of cells Structural hierarchy in the molecular organization of cells. The nucleus of this plant cell is an organelle containing several types of supramolecular complexes, including chromatin. Chromatin consists of two types of macromolecules, DNA and many different proteins, each made up of simple subunits.

Similarities among all types of cells All cells use nucleic acids (DNA) to store information Except RNA viruses, but not true cells (incapable of autonomous replication) All cells use nucleic acids (RNA) to access stored information All cells use proteins as catalysts (enzymes) for chemical reactions A few examples of RNA based enzymes, which may reflect primordial use of RNA All cells use lipids for membrane components Different types of lipids in different types of cells All cells use carbohydrates for cell walls (if present), recognition, and energy generation 34

How much biochemistry do you need to know for this course? Carbohydrates Lipids Proteins Nucleic Acids 1. You are expected to learn the structure and functions of these organic compounds: 2. You will be expected to learn the basic biochemical processes of major cell functions, such as respiration, protein synthesis and so on.

Topics 1 Introduction , amino acid and protein (8h) 2 Nucleic acid: Structure and properties (4h) 3 Carbohydrates: Structure and properties (2h) 4 Vitamins and coenzymes (4h) 5 Enzymes (6h) 6 Metabolism of carbohydrates (8h) 7 Assessment 8 Bioenergetics (4h) 9 Metabolism of lipids (8h) 10 Metabolism of amino acids (6h) 11 Integration of metabolism and review(2h)

6. Text book and references U Satyanarayana, Biochemistry Murray RK, Harper’s Illustrated Biochemistry, 26th ed. Nelson DL and Cox MM. Lehninger Principles of Biochemistry, 5th ed. 2008.

7. Some tips for study of biochemistry Inspiring interest, confidence Previewing and reviewing freshly Taking studying notes Discussing in groups Practice, crosstalk with other subjects Making use of internet

Just do as some proverbs say: “I hear, and I forget, I see, and I remember, I do, and I understand.” “Practice makes perfect” “No pains, no gains”

Final theory grade Final theory grade= First Assessment: 30~35% Final exam: 45~50% Daily performance: 20% Notice: 1/3 absent, can not take part in the final exam.