Chapter 1: Foundations of Biochemistry PDF

CHAPTER 1 The Foundations of Biochemistry Learning goals: 1. Distinguishing features of living organisms 2. Structure and function of the parts of the cell 3. Roles of small and large biomolecules 4. Energy transformation in living organisms 5. Regulation of metabolism...

CHAPTER 1 The Foundations of Biochemistry Learning goals: 1. Distinguishing features of living organisms 2. Structure and function of the parts of the cell 3. Roles of small and large biomolecules 4. Energy transformation in living organisms 5. Regulation of metabolism and catalysis 6. Coding of genetic information in DNA 7. Role of mutations and selection in evolution 1  Biochemistry Is the Chemistry of Living Matter Living matter is characterized by: 1. a high degree of complexity and organization 2. the extraction, transformation, and systematic use of energy to create and maintain structures and to do work 3. the interactions of individual components being dynamic and coordinated 4. the ability to sense and respond to changes in surroundings 5. a capacity for fairly precise self-replication while allowing enough change for evolution 2  Complexity and Organization Nucleus & Chromatin Large Secretory Vesicles 3 Living Organisms Must Intake and Transform Nutrients into Energy 4 Living Organisms Must Accurately Reproduce 5 Three Distinct Domains of Life Defined by Cellular and Molecular Differences That Evolved over Time Prokaryotes 6 Six Kingdoms of Life Defined by Organism, Cellular, and Molecular Differences Six kingdoms Cellular organization Archaea Unicellular prokaryote Bacteria Unicellular prokaryote Protista Unicellular eukaryote Energy Fungi Uni- or Multicellular eukaryote & Carbon Plantae Multicellular eukaryote Animalia Multicellular eukaryote 7  Cell: The Universal Building Block Living organisms are made of cells. The simplest living organisms are unicellular (single-celled). Larger organisms are multicellular (many-celled), with different functions for different cells. Cells have some common features but can contain unique components for different organisms. 8 All Cells Share Some Common Features 9 Bacterial Cell Structure Crystal Violet Stain 10  Components of Bacterial Cell Peptidoglycan: glycan strands cross-linked by short peptides Structure Composition Function Cell wall Carbohydrate + protein Mechanical support Cell membrane Lipid + protein Permeability barrier Nucleoid DNA + protein Genetic information Ribosomes RNA + protein Protein synthesis Pili Protein Adhesion, conjugation Flagella Protein Motility Cytoplasm Aqueous solution Site of metabolism 11  Eukaryote Cells: More Complexity 1. Have membrane-bound nucleus by definition: 1. protection for DNA; site of DNA metabolism 2. selective import and export via nuclear membrane pores 2. Have membrane-enclosed organelles: – mitochondria for energy in animals, plants, and fungi – chloroplasts for energy in plant – lysosomes for digestion of un-needed molecules 3. Compartmental segregation of energy-yielding and energy-consuming reactions helps cells to maintain homeostasis and stay away from equilibrium. 12 Animal and Plant Cells Contain Unique Components 13 Animal and Plant Cells Contain Unique Components 14  Animal and Plant Cells Contain Identical and Unique Components Plant Both Animal Membrane Chloroplast Nucleus and Nucleolus Vacuole Mitochondria Lysosome Glyoxysome Rough and Smooth ER Peroxisomes Plasmodesma Ribosomes Cell wall Golgi Cytoskeleton 15  Cytoplasm and Cytoskeleton Cytoplasm is a highly viscous solution where many reactions take place. Cytoskeleton consists of microtubules, actin filaments, and intermediate filaments. – cellular shape and division – intracellular organization – intracellular transport paths Myosin & Kinesin – cellular mobility Motor Protein 16  The Cytosol Is Very Crowded Folded proteins Translated peptide 17 Cytoskeleton Maintains Cellular Organization 18  Cellular Organization Is Dynamic, Changing Drastically at Different Stages 19  Biochemistry is the Chemistry of Living Matter The basis of all life is the chemical reactions that take place within the cell. Chemistry allows for: a high degree of complexity and organization the extraction, transformation, and systematic use of energy to create and maintain structures and to do work the interactions of individual components to be dynamic and coordinated the ability to sense and respond to changes in surrounding a capacity for fairly precise self-replication while allowing enough change for evolution 20 Organisms Can Also Be Classified by Different Energy and Carbon Sources chemolithotrophs photolithotrophs and and chemoorganotrophs photoorganotrophs All animals and fungi are 21 chemoorganoheterotrophic Living Systems Extract Energy From sunlight – plants – green bacteria – Cyanobacteria From fuels – animals – most bacteria Energy input is needed in order to maintain life. 22  The Molecular Logic of Life We look at the chemistry that is behind the: 1. initiation and acceleration of reactions 2. organization and specificity of metabolism and signaling 3. storage and transfer of information and energy 23 The Molecular Hierarchy of Structure 24 Biochemistry: Unique Role of Carbon 25  30 Elements Essential for Life Other than carbon, elements H, O, N, P, and S are also common. Metal ions (e.g., K+, Na+, Ca++, Mg++, Zn++, Fe++) play important roles in metabolism. 26 Common Functional Groups of Biological Molecules 27  Biological Molecules Typically Have Several Functional Groups Acetyl 28 The ABCs of Life 29 https://onlinelibrary.wiley.com/doi/epdf/10.1002/mabi.2 02300276 30  The Function of Molecules Strongly Depends on Three-Dimensional Structure Stereoisomers have different physical properties Geometric isomers (cis vs. trans) have different physical and chemical properties Enantiomers (mirror images) have identical physical properties (except with regard to polarized light) and react identically with achiral reagents Diastereomers have different physical and chemical properties 31 Cis vs. Trans 32 Cis vs. Trans 33 Enantiomers and Diastereomers Diastereomers (non-mirror images) 34 Enantiomers are labeled L and D 35 Enantiomers and Diastereomers 36 THALIDOMIDE Currently tested and used for it immunomodulatory, anti-angiogenic, and anti-inflammatory effects. 37 Dr. Frances Oldham Kelsey 38  Interactions Between Biomolecules Are Specific Macromolecules fold into 3D structures with unique binding pockets. Only certain molecules fit in well and can bind. Binding of chiral biomolecules is stereospecific. 39 Interactions Between Biomolecules Are Specific Hexokinase 40  Organisms Perform Energy Transductions to Accomplish Work to Stay Alive Living organisms exist in a dynamic steady state and are never at equilibrium with their surroundings. Energy coupling allows living organisms to transform matter into energy. Biological catalysts reduce energy requirement for reactions while offering specificity. As the entropy of the universe increases, creating and maintaining order requires work and energy. 41  Organisms Perform Energy Transductions to Accomplish Work to Stay Alive ∆S > 0 ∆Go < 0 catabolism ∆Go > 0 anabolism 42  How to Speed Reactions Up Higher temperatures − stability of macromolecules is limiting Higher concentration of reactants − costly, as more valuable starting material is needed Changing the reaction by coupling to a fast one − universally used by living organisms Lower activation barrier by catalysis − universally used by living organisms 43 Equilibrium and ΔG°Measure Spontaneity of a Reaction When chemical equilibrium is reached, are products or reactants If ΔGo < 0, then Keq > 1, more prominent. and products are favored at equilibrium. If ΔG°> 0, then Keq < 1, Tells us whether or and reactants are not a reaction occurs favored at equilibrium. spontaneously. 44  Unfavorable and Favorable Reactions Synthesis of complex molecules and many other metabolic reactions requires energy (endergonic). – A reaction might be thermodynamically unfavorable (G°> 0). Creating order requires work and energy. ‡ – A metabolic reaction might have too high an energy barrier (G > 0). Metabolite is kinetically stable. The breakdown of some metabolites releases a significant amount of energy (exergonic). – Such metabolites (ATP, NADH, NADPH) can be synthesized using the energy from sunlight and fuels. – Their cellular concentration is far higher than their equilibrium concentration. 45  Energy Coupling Chemical coupling of exergonic and endergonic reactions allows otherwise unfavorable reactions. The “high-energy” molecule (ATP) reacts directly with the metabolite that needs “activation.” 46 47  Free Energy Change in ATP Hydrolysis Coupled reactions can determine overall free energy changes. 48  Catalysis A catalyst is a compound that increases the rate of a chemical reaction. ‡ Catalysts lower the activation free energy G. Catalysts do not alter G° Enzymatic catalysis offers: – acceleration under mild conditions – high specificity – possibility for regulation 49 Enzymes Lower the Activation Energy to Increase the Reaction Rate 50 Series of Related Enzymatically Catalyzed Reactions Forms a Pathway Metabolic pathway produces energy or valuable materials Signal transduction pathway transmits information 51  Pathways Are Controlled in Order to Regulate Levels of Metabolites Example of a negative regulation: Product of enzyme 5 inhibits enzyme 1 to prevent wasteful excess products. 52  Genetic and Evolutionary Foundations Life on Earth arose 3.5–3.8 billion years ago. The formation of self-replicating molecules was a key step. Could it have been DNA? Could it have been proteins? 53 54  RNA World? RNA can act both as the information carrier and biocatalyst. Some viruses use RNA as a primary means of genetic information. 55 RNA Strands Peptide Strands DNA Strands 56  Complementarity in DNA Allows for Replication with Near-Perfect Fidelity 57  The Central “Dogma” of Biochemistry: DNA → RNA → Protein Genetic information flows only in one direction. 58  Natural Selection Favors Some Mutations Mutations occur more or less randomly in DNA and RNA. Mutated polynucleotides may be transcribed and translated into molecular machinery like proteins. Mutations that give organisms an advantage in a given environment are more likely to be propagated. 59 Natural Selection Favors Some Mutations 60 61 Evolution of Eukaryotes Could Also Be Mediated Through Endosymbiosis 62  Chapter 1: Summary In this chapter, we learned to: understand what defines living organisms relate structure and function of the cell realize that the structure of biomolecules often gives them specific functions grasp principles of bioenergetics review the forces behind evolution 63