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Biochemistry§ Major references1) BiochemistryGarrett & Grisham, 2nd or 3rd Edition (provided)2) Principles of Biochemistry, Lehninger, Nelson & Cox, 3rd edition3) Biochemistry, Stryer, 5th editionLIN Shengcai;E-mail: linsc@§ Content•Basic concepts of biochemistry•Biochemistry as a chemical science•Distinction between inanimate matter fromliving organisms•Biological molecules or biomolecules–Macromolecules and building blocks•Biochemistry as an interdisciplinary science• Biological forces• Dynamic cells•Water: the medium of lifeWhat Is Biochemistry?•B iochemistry seeks to describe the structure, organization, and functions of living matter in molecular terms.Roots (history) of Biochemistryz The present day biochemistry is the interweaving product of historical traditions of biochemistry, cell biology, and genetics.z Friedrich Wohler’s successful synthesis of urea from ammonium cyanate (1828)z Hans Buchner and Eduard Buchner’s discovery of in vitro fermentation in 1897, quite by accident. They were interested in manufacturing cell-free yeast extract for possible therapeutic use.These extracts had to be preserved without anticeptics at the time, and so they decided to try sucrose, a commonly used preservative in kitchen chemistry. They obtained a startling result: sucrose was rapidly fermented into alcohol by the yeast juice.•The significance of this finding is that they demonstrated for the first time fermentation could occur outside the cell. This was in contrast to the accepted view of their day, as asserted by Louis Pasteur, that fermentation was inextricably tied to living cells. The chance discovery opened up modern biochemistry. Metabolism became chemistry.•Crystallization of urease by JB Sumner in 1925•Cell Biology: Robert Hook’s observation of cells (1600’s);• Walter Flemming’s discovery of chromosomes (1875), identified as genetic material (1902)• Genetics: Gregor Mendel’s suggestion of gene as the unit of heredity (1800’s); Hershy and Chase’s demonstration of DNA as the genetic material (1950’s); Watson/Crick’s double helix (1953)Questions asked by biochemists• What are the chemical structures of the components of living matter?•How do the interactions of these components give rise to organized supramolecular structures, cells, multicellular tissues, andorganisms?•How does living matter extract energy from its surroundings in order to remain alive?•How does an organism store and transmit the information it needs to grow and to reproduce itself accurately?•What chemical changes accompany the reproduction, aging, and death of cells and organisms?•How are chemical reactions controlled inside living cells?The search for the answers is the study of the chemistry of life.Biochemistry as a multidisciplinary science Biochemistry draws its major themes fromThe major themesThe major themes:1. Organic chemistry, which describes the properties of biomolecules;2. Biophysics, which applies the techniques of physics to study thestructures of biomolecules;3. Medical research, which increasingly seeks to understand diseasestates in molecular terms;4. Nutrition, which has illuminated metabolism by describing thedietary requirements for maintenance of health;5. Microbiology, which has shown that single-celled organisms and viruses are ideally suited for studying many metabolic pathways and regulatory mechanisms;6. Physiology, which investigates life processes at the tissue andorganism levels;7. Cell biology, which describes the biochemical divisionof labor and life processes within a cell;8. Genetics, which describes mechanisms that give aparticular cell or organism its biochemical identity.What distinguishes living organisms from inanimatematter?•Living organisms are composed of lifeless molecules, which conform to all the physical and chemical laws that describe the behavior of inanimate matter. Yet living organisms possess extraordinary attributes not exhibited by any random collection of molecules. Biological chemistry is to study the properties of biomolecules that distinguish them from other collections of matter, and then identify the principles that characterize all living organisms.What distinguishes living organisms frominanimate objects?1. Degree of complexity: thousands of different molecules make up the intricate internal structures in a cell.2. Living organisms extract, transform, and use energy from their environment. The energy enables them to build and maintain their intricate structure or to do work. In contrast, inanimate matter does not absorb energy to do work; rather, it tends to decay towards a more disordered state, and reaches equilibrium with its surroundings.3. Living organisms are not at equilibrium with their surroundings.They use energy to concentrate ions from their surroundings, forexample.--The absorption of ions is an active process and consumes energy.4. A living organism is an open system5. A closed system: If the system exchanges neither matter norenergy with its surroundings, it is said to be closed.6. An open system: it exchanges both energy and material with itssurroundings. Living organisms use either of two strategies to derive energy from their surroundings:(1) they take up chemical fuels from the environment and extractenergy by oxidizing them; or(2) they absorb energy from sunlight.7. The capacity for precise self-replication and self-assembly—thequintessence of the living state.--Billions of daughter cells can carry a faithful copy of the genetic material of their parental cell. This replication is not quite like what Schrodinger believed in his “What Is Life”.Essence of life: “Life is for life”•Each component of a living organism has a specific function. This is true not only of macroscopic structures, such as leaves and stems or hearts and lungs, but also of microscopic intracellular structures such as the nucleus or chloroplast and of individual chemical compounds. The interplay among the chemical components of a living organism is dynamic; changes in one component cause coordinating or compensating changes in another, with the whole ensemble displaying a character beyond that of its individual constituents. The collection of molecules carries out a program, the end result of which is reproduction of the program andself-perpetuation of that collection of molecules; in short,life.--LehningerBioenergeticsA living organism must work to stay alive and reproduce themselves, which consumes energy. This comes to “bioenergetics”.Bioenergetics is about energy transformation and exchange. The central issue is the means by which energy from fuel metabolism is coupled to energy-requiring reactions.The major energy source adenosine triphosphate ATPActivation energyThe activation energy of a chemical reaction is the energy required to convert the reactant to transition state, which gives rise to product(s). In other words, it is the energy required to overcome the activation barrier.ΔG is the free energy change between the reactants and products.Free energy changesThe molecular logic of lifeThe molecular logic is the bio-molecular language that describes living processes in molecular terms. That is to say: we have to understand amino acids first in order to understand proteins and then protein complexes, protein structural motifs to understand protein functions, nucleotides to DNA and its replication; carbohydrates to polysaccharides, etc.Diversity in biomoleculesBiological Molecules (I): DNADeoxyribonucleotides (DNA)ChromatinHistones vs NonhistoneHistones are small, very basic proteins rich in lysine and arginine.The histones are the basic building blocks of chromatin structure.The nucleoids of prokaryotic cells also have proteins associated with DNA, but these proteins are quite different from the histones and do not seem to form a comparable chromatin structure.Nonhistone chromosomal proteins - The histones are accompanied by a much more diverse group of DNA-binding proteins callednonhistone chromosomal proteins.ChromosomesEukaryotic chromosomeBiological Molecules(II): Polysaccharides Polysaccharide name Monomeric UnitGlycogen D-GlucoseCellulose D-GlucoseChitin N-Acetyl-D-glucosamine Amylopectin (starch) D-Glucose (branched)Amylose (starch) D-Glucose (linear)Glucose•Glucose is a six carbon sugar which can provide a rapid source of ATP energy via glycolysis. Glucose is stored in polymer form by plants (starch) and animals (glycogen). Plants also have cellulose, which is not used to store glucose, but rather provides structural integrity to the cells. Glucose has an anomeric carbon, which can exist in the α and β configurations.Glucose can exist in both the D and L forms (though the D form predominates biologically).Structure of GlucosePolysaccharides•Polysaccharides containing a single sugar, such as glucose, are referred to as glucans. Others, which contain only mannose, are called mannans. Still others, containing only xylose, are called xylans.•Another group of polysaccharides of importance are heteropolysaccharides, derivatives of carbohydrates.•Example of polymers: CelluloseBiological Molecules (III): ProteinsAmino Acids•Amino acids are organic acids containing an amine group. They are the basic units of a protein. The most common amino acids are the L-α-amino acids.20 kinds of amino acids in our bodyTwo additional amino acids have beenidentifiedPeptide bondsBeta-sheetExample of polypeptide : IgGBiological molecules (IV): LipidsCholesterolLipid-soluble vitaminsChemical properties of biomoleculesz Chiralityz Bondingsz ForcesChiralityBiological forces for biomolecular interactions• In addition to covalent bonds, which hold atoms together to form molecules, there are weak forces, intramolecular or intermolecular.1. hydrogen bonds2. van der waals forces3. ionic interactions4. hydrophobic interactionsCovalent bond (e.g. peptide bond)Hydrogen bonding: a weak electrostatic attraction between electronegative atom and hydrogen covalently linked to an electronegative atomDipole-dipole interactionvan der Waals forces are the result of induced electrical interactions between closely approaching atoms. The positively charged nuclei are attracted to negatively charged electrons of nearby atoms.Weak, and do not have a fixed geometry compared to dipole-dipole interaction.H2O: the medium of lifeBiological functions of water•Because of its unique chemical and physical characteristics, water plays several key roles in metabolic processes. It serves as a solvent for many chemical compounds, a medium in which many chemical reactions occur, even as a reactant or product in many reactions.•As water is diffusible through the semipermeable membrane, it is critical for adjusting osmotic differences. Therefore, water can help prevent cells (organisms) from burst (osmotic lysis). Temperature adjustment, waste removal, lubrication for joints, etc..Water, H2O•Water is the most abundant substance in living systems, making up 70% or more of the weight of most organisms;•Water has a higher boiling point and heat energy of vaporization than most other common solvents.•Water participates in many biological reactions (e.g. hydrolysis). •The dipolar nature of water provides hydrogen bonding.•Water as a solvent:–uncharged but polar biomolecules such as sugar dissolvereadily in water because of the stabilizing effect of hydrogenbonds between the hydroxyl or carbonyl oxygen and the polarwater molecules.–Water interacts electrostatically with charged solutes, such asNa+Cl-。