Chapter 3 (Part 1) - Chemical Reactions and Enzymes PDF

Metabolic Reactions and Enzymes Chapter 3 Interactions Between Proteins and Ligands Interactions Between Proteins and Ligands Ligand: any molecule or ion that is bound to a protein by one of the following weak physical forces: Hydrogen bonds Ionic bonds van der Waals force...

Metabolic Reactions and Enzymes Chapter 3 Interactions Between Proteins and Ligands Interactions Between Proteins and Ligands Ligand: any molecule or ion that is bound to a protein by one of the following weak physical forces: Hydrogen bonds Ionic bonds van der Waals forces Hydrophobic forces between non-polar regions Binding site: region of a protein where a ligand binds Ligand binding typically changes protein conformation Protein function activated or inhibited Affinity Affinity: strength of the interaction between ligand and protein The higher the affinity, the less of the ligand is required to bind to the protein Chemical Specificity Protein binding sites are often very specific to particular ligands Determined by the amino acids in the binding site and corresponding shape Other binding sites are less specific & can bind several related ligands Saturation The fraction of total binding sites that are occupied at any given time 100% saturated when all binding sites are occupied Depends on: Concentration of unbound ligand in solution Affinity of binding site for ligand Competition More than one ligand can bind to certain binding sites → ligands have to compete for binding Metabolic Reactions Chemical Reactions Metabolism: the sum of all chemical reactions that occur in the body Anabolism: synthesis of organic molecules Catabolism: breakdown of organic molecules Chemical reactions: any time chemical bonds are formed, broken and rearranged, or electrons are transferred between two or more atoms or molecules A+B⇌ C+D Reactants/substrates ⇌ Products Focus on reactions that transfer energy or use stored energy to do work Involve an exchange of energy: Exergonic vs. endergonic reactions  Chemical Reactions Energy-Releasing Reaction Energy-Requiring Reaction Exergonic reaction Endergonic reaction Catabolic (ex: protein catabolism) Anabolic (ex: synthesis of proteins) Proceeds spontaneously Does not proceed spontaneously Energy in reactants > energy in products Energy in reactants < energy in products Reactants → Products + Energy Released energy may power an energy- Energy input required: requiring reaction Reactants + Energy → Products Exergonic vs. Endergonic Reactions Energy in Biological Reactions Classifications for Metabolic Reactions Types Anabolic/Synthesis: Exchange: Catabolic/Decomposition: production of larger atoms or electrons molecular breakdown molecules from smaller exchange AB → A+B reactants AB + CD → AC + BD + A + B→ AB energy Metabolic Reactions in the Body 1) Hydrolysis and dehydration synthesis/condensation 2) Phosphorylation and dephosphorylation 3) Oxidation-reduction Hydrolysis and Dehydration Synthesis/ Condensation Function: Synthesis and breakdown of some biomolecules Hydrolysis: A–B + H2O → A–OH + H–B sucrose + H2O → glucose + fructose Dehydration synthesis/Condensation: A–OH + H–B → A–B + H2O glucose + fructose → sucrose + H2O Phosphorylation and Dephosphorylation Phosphorylation: A + Pi → A–P ex: ADP + Pi → ATP + H2O Function: Formation of nucleotides for energy storage in phosphate bond Phosphorylation of a protein to change its shape Dephosphorylation: A–P → A + Pi ex: ATP + H2O → ADP + Pi (also a hydrolysis reaction)  Oxidation-Reduction Reactions *Oxidation and reduction are always coupled* Oxidation: Removal of electrons A + B ⇌ A + B (where is an electron) A is oxidized (loses electron) B is reduced (gains electron) Or Removal of Hydrogen atoms (each H atom carries an electron) H2 → 2 H+ + 2 e– HA-BH ⇌ A=B + 2H Oxidation-Reduction Reactions Reduction: Addition of electrons 2 H + + 2 e– → H 2 or Addition of hydrogen atoms A=B + 2 H ⇌ HA-BH Chemical Equilibrium Equilibrium in chemical reactions: when the rates of the forward and reverse reactions are equal (when there is no net reaction direction) Reactant is converted to the product at the same rate the product is converted to the reactant Reached when the energy levels of reactants and products are equal, not when the concentration of reactant equals the concentration of product  Reversible and Irreversible Reactions Forward Reactants Products Reverse Chemical equilibrium: forward and reverse reaction rates are equal The ratio of product concentration to reactant concentration at equilibrium depends on the amount of energy released or added during the reaction Irreversible reactions: reactions that release large quantities of energy Reaction Rate The speed with which a reaction takes place Reaction rates must match the body’s needs at that moment Determined by 4 factors: 1. Concentration of reactants and products (Law of Mass Action) 2. Activation energy: amount of energy to destabilize the reactants to allow the reaction to happen (Enzymes lower the activation energy) 3. Temperature 4. Presence of a catalyst Law of Mass Action Reactant and product concentrations affect the direction in which the net reaction proceeds Increased reactant concentration or decreased product concentration → increases formation of products Increased product concentration or decreased reactant concentration → increases formation of reactants Activation Energy Amount of energy to destabilize the reactants to allow reaction to happen Reactant molecules must acquire enough energy to overcome the mutual repulsion of the electrons surrounding the atoms in each molecule Activation Energy Energy comes from collisions between molecules Energy must be equal to or greater than the activation energy Reaction rate increases as activation energy barrier decreases Enzymes lower activation energy Enzymes Proteins that act as catalysts to lower activation energies in chemical reactions in living organisms Can catalyze the same reaction repeatedly Not changed by the reaction and do not change the chemical equilibrium of the reaction Characteristics of Enzymes Enzyme Substrate Specificity Substrate specificity is dependent on the complementary shapes of the enzyme active site + substrate molecules Two models for substrate interaction: Enzyme Examples Cofactors and Coenzymes Cofactor: substance that binds to an enzyme and is necessary for the enzyme’s activity, allows substrate to bind to active site Ex: trace metals (magnesium, iron, zinc, copper) or vitamins Coenzyme: organic vitamin-derived cofactor that directly participates in a reaction as one of the substrates by transferring chemical groups during the reaction No catalytic activity Not consumed in the reaction and can be reused Derived from vitamins Coenzyme Vitamin Group NADH niacin (B3) electron carrier FAD riboflavin (B2) electron carrier CoA pantothenic acid (B5) acetyl Regulating Enzyme-Catalyzed Reactions Enzymatic activity is measured by the rate at which reactant is converted to product Factors affecting the rates of enzyme-catalyzed reactions: Catalytic rate of enzyme (can vary from one enzyme to another) Substrate concentration Enzyme concentration Affinity Temperature and pH (normally constant) Also influenced by concentration of cofactors and coenzymes Substrate Concentration Rate of reaction increases as substrate concentration increases, until enzyme saturation (maximum rate) Enzyme Concentration Increasing enzyme concentration can increase reaction rate at any substrate concentration Cell changes enzyme concentration by changing the rate of enzyme (protein) synthesis or breakdown Affinity Higher affinity of substrate molecules to the active site result in high rates for enzyme-catalyzed reactions Temperature & pH Temperature pH Regulation of Enzyme Activity The rates of metabolic reactions are continually adjusted to meet the body’s needs 1. Changes in protein synthesis and degradation determines types and amounts of protein in a cell (time-consuming) 2. Change the activity of existing enzymes (rapid regulation) Changing protein shape alters protein function (affects binding site characteristics and ligand binding) Allosteric or covalent modulation alters the enzyme’s active site (ex: phosphorylation) Changing Protein Shape 1. Allosteric regulation: if a protein contains more than one binding site, binding of a ligand to a regulatory/allosteric site can alter the shape of the active site Can either increase or decrease activity (activators or inhibitors) Some enzymes contain multiple regulatory sites Changing Protein Shape 2. Covalent regulation: the covalent bonding of a chemical group to an amino acid side chain can alter protein shape and therefore the enzyme’s activity Phosphorylation: phosphate group transferred from one molecule to another Can increase or decrease functional activity Active site Phosphorylation Protein kinase: enzymes that catalyze the transfer of a phosphate from ATP to a protein’s side chain Protein phosphatase: enzymes that remove the phosphate group The activity of many proteins depends on relative kinase and phosphatase activity Metabolic Pathways A sequence of enzyme-mediated reactions leading to the formation of a particular product A→B→C→D… Rate-limiting reaction: the step with the slowest reaction rate in a metabolic pathway Rate-limiting enzymes are often the sites of allosteric or covalent regulation Allows cells to control an entire pathway by regulating only one enzyme Often regulated by feedback or end-product inhibition Metabolic Pathways Metabolic Pathways: Feedback Inhibition Intermediate product or end-product allosterically inhibits a previous enzyme in the same pathway Holds reactions at a steady state and respond to body’s needs The first enzymes after branch points are regulated in metabolic pathways Inborn Errors of Metabolism A mutation in a single gene that codes for an enzyme in a metabolic pathway Failure of the metabolic pathways involved in either the breakdown or storage of carbohydrates, fatty acids and proteins Products to be formed after this enzyme in the chain are not formed Diseases are caused by: Loss of end-product Accumulation of intermediary products or alternative products in a branch Inborn Errors of Metabolism