Foundation of Biochemistry Biological and chemical background to biochemistry Molecular Logic of Life (生命的分子逻辑) •The Chemical Unity (化学一致性)of Diverse Living Organism •Energy Production and Consumption in Metabolism •Biological Information Transfer (生物信息的传递) Biomolecules (生物分子) •Chemical Composition (化学成分) •Three Dimensional Structure (三维结构) •Chemical Reactivity (化学反应活性) •Macromelecules and Their Monomeric Subunits (大分子与单体亚基) 一、Biological and chemical background to biochemistry (生化的生物学和化学基础) •Living organisms operate within the same physical laws that apply to all natural processes •Cell, the units of all living organisms; Nearly all of the organic compounds (from which living organisms are constructed) are products of biological activity (生命活动) •Water is the medium (介质) in which the first cells arose, and the solvent (溶剂) in which most biochemical transformations (生化变化) occur. 二、Molecular Logic of Life Molecules of organisms confirm to all familiar laws of chemistry (化学规律), they also interact with each other in accordance with another set of principles (法则), which we shall refer to collectively as Molecular Logic of Life • The Chemical Unity of Diverse Living Organism 生命多样性的化学一致性 1. Living mater has several characteristics (特性) • Structurally complicated and highly organized • Extract(吸收), transform(转化), and use energy from their environment (chemical or sunlight), to build and maintain their own intricate structures and to do mechanical, chemical, osmotic, and other types of work • Capacity for precise self-replication(自我复制) and self-assembly(自组装), a property that can be regarded as the quintessence (精髓) of living state 2. Biochemistry seek to explain life in chemical terms(化学术语) 3. Chemical unity underlines biological diversity (化学的一致性是生物多样性的基础) 4. All macromolecules(大分子) are constructed from a few simple compounds •Energy Production and Consumption in Metabolism 1. Organisms are never at equilibrium (平衡) with their surroundings 2. Molecular composition reflects a dynamic steady state (动子学稳态) 3. Organisms exchange energy and matter with their surroundings 4. Cell and organisms interconvert(转换) different forms of energy 5. The flow of electrons (电子流动) provides energy for organisms 6. Energy promotes (推动) sequences of chemical reactions 7. ATP is the universal carrier (通用载体) of metabolic energy, linking catabolism and anabolism 8. Metabolism is regulated to archive balance and economy •Biological Information Transfer (生物信息的传递) 1. Genetic continuity is vested (被赋予) in DNA molecules Perhaps the most remarkable of all the properties of living cells and organisms is their ability to reproduce themselves with nearly perfect fidelity (保真) for countless generations 2. The structure of DNA allows for its repair and replication with near-perfect fidelity Genetic information is encoded in the linear sequence of four kinds of subunits of DNA. The double-helical (双螺旋) DNA molecule contains an internal (内在的) template for its own replication and repair 3. Changes in hereditary (遗传的) instructions allow evolution 4. The linear sequence in DNA encodes protein with three-dimensional structures(三维结构) DNA RNA Protein folds Particular three dimensional structure (Native conformation, 天然构象) Native conformation is crucial to its function as either catalyst (催化剂) or structural element Native conformation is crucial to its function as either catalyst (催化剂) or structural element This principle: The linear sequence of amino acids in a protein leads to the acquisition of a unique threedimensional structure by a self assembly process Individual macromolecules with specific affinity (亲合性) for other macromolecules self-assemble into supramolecular complexes. 5. Noncovalent (非共价的) interactions stabilize threedimensional structures Three dimensional biological structures combine the properties of flexibility () and stability Noncovalent interactions are also central to the specificity and catalytic efficiency of enzymes The formation of oncovalent interactions provides the energy for self-assembly of macromolecules by stabilizing native conformation relative to unfolded, random forms. Summary : The physical roots of the biochemical world. We can now summarize the various principles of the Molecular Logic of Life: 1. A living cell is a self-contained (控制), selfassembly, self-adjusting (调节), self-perpetuating (使 自身永存) isothermal (恒温的) system of molecules that extracts free energy and raw materials from its environment. 2. The cell carries out many consecutive reactions promoted by specific catalysts, called enzymes, which it produces itself. 3. The cell maintains itself in a dynamic steady state, far from equilibrium with its surroundings. 4. self-replication through many generations is ensured by the self-repairing, linear information-coding system. 5. Many weak (noncovalent) interactions, acting cooperatively, stabilize the three-dimensional structures of biomolecules and supramolecular complexes. 6. Stereospecificity (立体专一性) is characteristic feature of the molecular logic of living cells. 三、Biomolecules Chemical composition of living mater 1. Living mater is composed mostly of the lighter elements 2. Biomolecules are compounds of carbon Molecules containing covalently bonded carbon backbones are called organic compounds. 3. Functional groups determine chemical properties Three dimensional structure 1. Each cellular component has a characteristic three-dimensional structure 2. Most biomolecules are asymmetric 3. Interactions between biomolecules are stereospecific Chemical reactivity 1. Bond strength is related to the electronegativities(电负性) of the bonded atoms Strengths of bonds common in biomolecules Types of bonds Single bonds O-H H-H P-O C-H N-H C-O C-C S-H C-N N-O S-S Bond dissociation energy (KJ/mol) 461 435 419 414 389 352 348 339 293 222 214 Types of bonds Double bonds C=O C=N C=C P=O Triple bonds C C N N Bond dissociation energy (KJ/mol) 712 615 611 502 816 930 Noncovalent bonds or interactions Hydrogen bonds, Van der waals force, hydrophilic interaction, hydrophobic interactions, Ionic interactions: 4-20 2. Five types of chemical transformations occur in cells Most cells have the capacity to carry out thousands of specific, enzyme-catalyzed reactions: * Transformate of simple nutrients such as glucose into amino acids, nucleiotides, or lipids * Extraction of energy from fuels by oxidation * or polymerization of subunits into macromolecules 2. Five types of chemical transformations occur in cells • Functional group transfer • Oxidations and reductions • Rearrangement • Cleavage (reactions that form or break carbon-carbon bonds • Condensation (reactions in which two molecules condense, with the elimination of a molecule of water ) Reactions within one category generally occur by similar mechanism Macromolecules and their monmeric subunits 1. The major constituents of organisms are macromolecules Macromolecules MW Proteins 5,000- over millions Nucleic acids to several billions Polysaccharides to millions Lipids 750-1,500/individual 2. Monmeric subunits have simple structures Most larger structures in cells are constructed from 33 organic compounds with molecular weight of 500 or less: The ABCs of Biochemistry * 20 amino acids of protein * 5 nitrogenous bases: uracil, thymine, cytosine, adenine, quanine * 2 five-carbon sugars: α- D-ribose, 2-deoxyl-α-D- ribose * 1 six-carbon sugar: glucose * 1 phosphoric acid * 4 components found in many membrane lipids: Oleic acid (18:1); Palmitic acid (16:0); Choline; Glycerol Gly Ala Leu , Pro , Val Ile Met Ser , Cys Thr Asn , Gln Phe Tyr Trp or Try Lys Arg His Asp Glu Purine, Pu (嘌呤碱) Pyrimidine, Py (嘧啶碱) HOH2C O OH H H OH H OH H β-D-ribose (β-D-核糖) (D-核糖) HOH2C O H OH H H OH (2-D-脱氧核糖) H H β-D-2-deoxyribose (β-D-2-脱氧核糖) (油酸) (棕榈酸) phosphoric acid: -O Choline H0 Glycerol