The Foundations of Biochemistry PDF

The foundations of biochemistry  The foundations of Biochemistry 1. Introduction 2. Chemical foundations 2.1. Bioelements 2.2. Three-dimensional structure: Configuration & Conformation 3. Water, the solvent of life 3.1. Water and hydrogen bonding 3.2. Water as a solvent 3.3....

The foundations of biochemistry  The foundations of Biochemistry 1. Introduction 2. Chemical foundations 2.1. Bioelements 2.2. Three-dimensional structure: Configuration & Conformation 3. Water, the solvent of life 3.1. Water and hydrogen bonding 3.2. Water as a solvent 3.3. Ionization of water and (pH) and Buffering systems 1. Introduction What is the aim of Biochemistry? “Biochemistry Study the structure, organization and functions of all organisms from a molecular point of view “How the remarkable properties of living organisms arise from thousands of different molecules” A high degree of chemical complexity and microscopic organization Systems for extracting, transforming, and using energy from the environment A capacity for precise self-replication and self-assembly  Structural Metabolic Biochemistry Biochemistry Molecular Biology Diverse living organism share common chemical features: gradual evolution “Anything found to be true of E. coli must also be true of elephants” Jacques Monod , 1954 “Biochemical unity” Cells Are the Structural and Functional Units of All Living Organisms Structural hierarchy in the molecular organization of cells 2. Chemical Foundations 2.1. Bioelements Elements Essential to Life and Health Primary Bioelements: H,O,C,N ELEMENT % TOTAL % DRY WEIGHT Hydrogen 63 5.7 Oxygen 25.2 9.3 Carbon 9.5 61.7 Nitrogen 1.4 11 Primary Bioelements: H,O,C,N ELEMENT % TOTAL % DRY WEIGHT Hydrogen 63 5.7 Oxygen 25.2 9.3 Carbon 9.5 61.7 Nitrogen 1.4 11 Biomolecules Are Compounds of Carbon with a Variety of Functional Groups carbon can form covalent single, double, and triple bonds  Geometry of Carbon Bonding carbon atoms have a characteristic tetrahedral arrangement of their four single bonds free rotation around each single bond limited rotation about the axis of a double bond Common functional groups Many Biomolecules Are Polyfunctional  Hydrocarbons are made of hydrogen and carbon atoms Alkanes: saturated hydrocarbons (w/o double bonds) Number Name of C 1 Methane 2 Ethane Methane (1C) Ethane (2C) Propane (2C) 3 Propane 4 Butane 5 pentane 6 Hexane 7 Heptane 8 Octane 9 Nonane 10 Decane Alkenes have 1 double bond (Unsaturated). Ex: Ethene Alkynes have 1 triple bond (Unsaturated). Ex: Ethyne  Alcohols show a hydroxyl group (-OH) Number of C Hydrocarbon Alcohol 1 Methane Methanol 2 Ethane Ethanol Alcohols are 3 Propane Propanol named with the 4 Butane Butanol suffix –ol to the 5 Pentane Pentanol parent alkane 6 Hexane Hexanol 7 Heptane Heptanol 8 Octane Octanol 9 Nonane Nonanol 10 Decane Decanol Aldehydes and Ketones show a carbonyl group Nomenclature Suffix to the parent alkane: –al Ex: Methanal, Ethanal, propanal, butanal, formaldehyde acetaldehyde Suffix to the parent alkane: –one Ex: propanone, butanone, acetone Carboxylic acids show a carboxyl group Suffix to the parent alkane: –oic Ex: Methanoic acid, Ethanoic acid, propanoic acid, butanoic acid, Formic acid Acetic acid If the acid is deprotonated we add suffix -ate: Acetate Amines are organic compounds that contain an amino group Amines are weak organic bases. At neutral pH they can be protonated  Oxidation: loss of electrons Reduction: gain of electrons When one of the reactants is oxygen, then oxidation is the gain of oxygen. Reduction is a loss of oxygen. C more reduced Oxidation Reduction C more oxidized Ether bond: Two organic radicals linked through an Oxygen atom  Ester bond: When a Carboxylic acid group reacts with an alcohol Amide bond: When a Carboxylic acid group reacts with an amine S bound to H is a Sulfhydryl or thiol group Thiol group Two thiol groups can react and be bound through a Disulfide bond Disulfide A carboxylic group and a thiol group can react forming a thioester bond Thioester 2. Chemical Foundations 2.2. Three-dimensional structure: Configuration & Conformation Three-Dimensional Structure Is Described by Configuration and Conformation configuration = the fixed spatial arrangement of atoms stereoisomers = molecules with the same chemical bonds and same chemical formula interconversion between stereoisomers requires breakage of covalent bonds  Configurations of Geometric Isomers geometric isomers, or cis-trans isomers = differ in the arrangement of substituent groups with respect to the double bond  Chiral and Achiral Molecules chiral centers = asymmetric carbons a molecule can have 2n stereoisomers, where n is the number of chiral carbons Configuration nomenclature Enantiomers and Diastereomers enantiomers = stereoisomers that are mirror images of each other diastereomers = stereoisomers that are not mirror images of each other Optical Activity of Enantiomers enantiomers have nearly identical chemical reactivities, but differ in optical activity a racemic mixture (equimolar solution of two enantiomers) shows no optical rotation Interconversion between stereoisomers requires breakage of covalent bonds In nature only one of the enantiomers is usually present  In nature only one of the enantiomers is usually present D-monosaccharides L-aminoacids Interactions between Biomolecules Are Stereospecific stereospecificity = the ability to distinguish between stereoisomers  Molecular Conformation conformation = the spatial arrangement of substituent groups that are free to assume different positions in space 3. Water, the solvent of life 3.1. Water & Hydrogen bonding Hydrogen Bonding Gives Water Its Unusual Properties water has a higher melting point, boiling point, and heat of vaporization than most other common solvents hydrogen bond = electrostatic attraction between the oxygen atom of one water molecule and the hydrogen of another Unequal electron sharing between O and H e- 2 Electric dipoles e- H bonds: electrostatic attraction between the molecules of water 23 kJ/mol 470 kJ/mol  H bonds: Non-covalent weak interaction Covalent bonds involve the sharing of electron pairs between atoms Non-covalent “weak” interactions do not involve the sharing of electron pairs between atoms  Number of Hydrogen Bonds Formed in liquid, each H2O molecule forms hydrogen bonds with an average of 3.4 other molecules in ice, each H2O molecule forms 4 hydrogen bonds  Hydrogen bonds are not unique to water H atom covalently bonded to another Electronegative electronegative atom atom Some biologically important hydrogen bonds Directionality of the hydrogen bond  Weak Interactions Are Crucial to Macromolecular Structure and Function noncovalent interactions are much weaker than covalent bonds continually forming and breaking Macromolecules and supramolecular complexes stability rely on weak interactions Multiple weak bonds stabilize large molecule interactions 3. Water, the solvent of life 3.2. Water as a solvent Water Interacts Electrostatically with Charged Solutes hydrophilic = describes compounds that dissolve easily in H2O; generally charged or polar compounds hydrophobic = nonpolar molecules such as lipids and waxes amphipathic = contain regions that are polar (or charged) and regions that are nonpolar  Polar, Nonpolar, and Amphipathic Biomolecules  Water as Solvent H2O dissolves salts and charged biomolecules by screening electrostatic interactions the increase in entropy of the system is largely responsible for the ease of dissolving salts in water  Nonpolar Gases Are Poorly Soluble in Water biologically important gases CO2, O2, N2 are nonpolar their movement into aqueous solution decreases entropy by constraining their motion  Amphipathic Compounds in Aqueous Solutions polar, hydrophilic region interacts favorably with H2O and tends to dissolve nonpolar, hydrophobic region tends to avoid contact with H2O and cluster together  The Hydrophobic Effect hydrophobic effect = – nonpolar regions cluster together – polar regions arrange to maximize interactions with each other and with the solvent micelles = thermodynamically stable structures of amphipathic compounds in water  Phospholipids spontaneously assemble via multiple noncovalent interactions to form different structures in aqueous solutions  Solutes alter physical properties of the solvent, water: vapor pressure, boiling and melting point, osmotic pressure Cells generally have higher osmolarity* than their surroundings Osmolarity* depends on the number of dissolved particles, not in their mass 3. Water, the solvent of life 3.3. Ionization of water (pH) and buffering systems Pure Water Is Slightly Ionized The ion product of water (Kw) is constant The pH Scale Designates the H+ and OH– Concentrations Table 2-5 The pH Scale the pH scale is based on the [H+] (M) pH [OH–] (M) pOHa ion product of water, Kw 100(1) 0 10–14 14 10–1 1 10–13 13 10–2 2 10–12 12 the term pH is defined by the 10–3 10–4 3 4 10–11 10–10 11 10 expression 10–5 5 10–9 9 10–6 6 10–8 8 10–7 7 10–7 7 4 10–8 8 10–6 6 pH = log. = –log [H+] ^K ‘ 10–9 9 10–5 5 10–10 10 10–4 4 10–11 11 10–3 3 for a precisely neutral solution 10–12 10–13 12 13 10–2 10–1 2 1 at 25 °C, pH = 7.0 10–14 14 100(1) 0 aThe expression pOH is sometimes used to describe the basicity OH– concentration of a solution; pOH is defined by the expression pOH = –log [OH–], which is analogous to the expression for pH. Note that in all cases, pH + pOH = 14 An acid is a compound capable of donating a proton (proton donor) Acetic acid acetate acid base A base is a compound capable of accepting a proton (proton acceptor) Conjugate acid-base pair: proton donor / proton acceptor  Week acids and bases are not completely ionized when dissolved in water Conjugate acid-base pair: proton donor + proton acceptor  Ionization Constants the tendency for any acid (HA) to lose a proton and form its conjugate base (A−) is defined by the equilibrium constant (Keq) for the reversible reaction HA ⇌ H+ + A− for which ^K. ‘^D ‘ Keq = = Ka ^KD‘  pKa pKa = analogous to pH and defined by the equation 4 pKa = log = −log Ka Nd the stronger the tendency to dissociate a proton, the stronger the acid and the lower its pKa pKa can be determined experimentally  The Titration Curve of Acetic Acid at the midpoint, the pH of the equimolar solution = the pKa of acetic acid  Comparison of the Titration Curves of Three Weak Acids a weak acid and its anion—a conjugate acid-base pair—can act as a buffer  Buffers Are Mixtures of Weak Acids and Their Conjugate Bases buffers = aqueous systems that tend to resist changes in pH when small amounts of acid (H+) or base (OH–) are added a buffer system consists of a weak acid (the proton donor) and its conjugate base (the proton acceptor)  The Henderson-Hasselbalch Equation Relates pH, pKa, and Buffer Concentration Henderson-Hasselbalch equation = describes the shape of the titration curve of any weak acid [A - ] pH = p k a + log (Eqn 2-9) [HA] Weak Acids or Bases Buffer Cells and Tissues against pH Changes proteins containing histidine (side chain pKa of 6.0) residues buffer effectively near neutral pH The Phosphate Buffer System the phosphate buffer system acts in the cytoplasm of all cells: H2PO4− ⇌ H+ + HPO42− HPO42− acts as a proton donor and HPO42− acts as a proton acceptor buffer system is maximally effective at a pH close to its pKa of 6.86 – works over a range between 5.9 and 7.9 The Bicarbonate Buffer System Involves Three Reversible Equilibria the rate of respiration (controlled by the brain stem) can quickly adjust these equilibria to keep the blood pH nearly constant hyperventilation raises blood pH