Lecture 1 Introduction, Noncovalent Bonds, and Properties of Water Reading: Berg, Tymoczko & Stryer: Chapter 1 problems in textbook: chapter 1, pp. 23-24, #1,2,3,6,7,8,9, 10,11; practice problems at end of Gen Chem Review Key Concepts in Biochemistry Cells -- important structural features; compartments (plasma membrane, nucleus or nucleoid, cytoplasm, ribosomes, organelles like mitochondria, chloroplasts, endoplasmic reticulum and Golgi apparatus Chemical unity of living systems Transformation of energy and matter from surroundings - -> complex, orderly structures Biomolecules -- functional groups; condensation reactions Proteins -- molecular workhorses of living systems Enzymes increase rates of biological reactions to permit life on a biological timescale. Rates of processes exquisitely regulated to maintain dynamic steady state. 3-D structures of biomolecules determine their functions -- role of noncovalent interactions in structure and function. and Properties of Water 1
Key Concepts, continued Noncovalent interactions: ionic interactions, hydrogen bonds, van der Waals interactions, hydrophobic interactions individually much weaker than covalent bonds collectively very strong crucial to structures and functions of biomolecules Properties of water -- solvent /milieu for living systems Most biomolecules have functional groups that are weak acids or bases, whose ionization properties are crucial to structures and functions of the molecules; ph determines state of ionization of biomolecular weak acids and bases. Buffers (intracellular and extracellular) Learning Objectives Review basic structures of cells and organelles -- important structural features and compartments (nucleus or nucleoid, plasma membrane, cytoplasm, ribosomes, mitochondria, chloroplasts, and endoplasmic reticulum). Review (from posted lecture notes here) functional groups important in biomolecules, and condensation reactions involving some of these functional groups. List and explain the characteristics of 4 types of noncovalent interactions important in structures and interactions of biomolecules. Answer the following questions: 1. What is an ionic interaction (charge-charge interaction), and what other terms are used to describe the same thing? How does the distance between two charged groups affect the energy of their interaction? What are the relative values of the dielectric constants for a nonpolar solvent and a polar solvent? How does solvent polarity affect strength of ionic interactions? What type of solvent is water? Is an ionic interaction stronger in a polar solvent or in a nonpolar solvent? and Properties of Water 2
Learning Objectives, continued (Noncovalent interactions, continued) 2. What is a hydrogen bond, what is a hydrogen bond donor, and what is a hydrogen bond acceptor? How does the strength of a hydrogen bond relate to its directionality? Be able to identify chemical groups (and the specific atoms involved) that can serve as hydrogen bond donors and groups which can serve as hydrogen bond acceptors. [Do not confuse a hydrogen bond donor with a proton donor (Bronsted acid).] 3. What are van der Waals interactions? How (qualitatively, not an equation) does their strength relate to the distance between atoms? Why are such weak, nonspecific interactions important in biochemistry? 4. What is the hydrophobic effect? Explain the idea of hydrophobic interactions" and the roles they play in biological systems. (Roles will become more apparent as the semester progresses). Learning Objectives, continued Explain the properties of H 2 O (its ionization properties, polarity, hydrogen bonding ability, and solvent properties) that are so important to its role as the major constituent of living systems. Explain: titration curve, buffer, and pk a. Relate the strength of a weak acid to its pk a. Write out the 3 acid dissociation reactions of phosphoric acid, and write out condensation reactions showing formation of a phosphomonoester and of a phosphodiester. See practice problems at end of Gen Chem Review notes: http://www.biochem.arizona.edu/classes/bioc460/spring/460web/l ectures/chem_review/generalchemrev460-08.pdf Explain relationships between (and be able to do calculations involving these relationships): 1. [H + ] and ph 2. K a (acid dissociation constant) and pk a 3. ratio of [conjugate base]/[conjugate acid] and ph and pk a 4. ratio of [conjugate base/[conjugate acid] and fraction or percent of a functional group that's in the form of the conjugate acid or the conjugate base. and Properties of Water 3
Bacterial Cells BRIEF REVIEW OF CELL STRUCTURE Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig.1-6 Eukaryotic Cells Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig.1-7a and Properties of Water 4
Eukaryotic Cells Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig.1-7b Functional Groups in Biomolecules and Properties of Water 5
Functional Groups in Biomolecules Condensation and Hydrolysis Reactions 1. Esters and Properties of Water 6
Condensation and Hydrolysis Reactions 2. Amides Condensation and Hydrolysis Reactions 3. Anhydrides and Properties of Water 7
Chemical Bonds/Interactions in Biomolecules Covalent bonds: single, double, (triple) 2 atoms share a pair of electrons to fill an orbital on each atom Equal or nearly equal sharing --> nonpolar group or molecule Examples: C C and C H bonds (not polar) Unequal sharing --> a polar group or molecule 1 atom has partial positive charge (δ+) other atom has partial negative charge (δ ) Example: an O H bond (polar) Interaction energy (bond energy): the energy released during formation of the bond/interaction (so that much energy would have to be put in to break the bond). from Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed.) and Properties of Water 8
Ionic Interactions (charge-charge interactions, salt bridges): electrostatic attraction or repulsion between charged groups Coulomb s Law: E = Energy of interaction q s = charges D = dielectric constant (1 for vacuum, ~2 for hexane, ~80 for H 2 O) r = distance between charged atoms k = proportionality constant; value depends on units desired for expressing energy Hydrogen Bonds Electrostatic effect of polarity of solvent (D) Donor groups Acceptor groups N-H -----> N: <---- O-H -----> O: <---- Directional and Properties of Water 9
van der Waals Interactions Energy of a van der Waals interaction as 2 atoms approach one another within about 4-5 Å Individually very weak and nonspecific, but sum of many can be very important in steric (shape) complementarity Berg et al., Fig. 1.10 and Properties of Water 10
Hydrophobic "Interactions" hydrophobic effect, the "oil drop" effect association of nonpolar groups with each other in aqueous systems due to the unfavorable interaction of nonpolar groups/molecules with water Result: "preference" of hydrophobic groups and molecules to minimize their exposure to water misnamed " hydrophobic 'interactions' " Berg et al. Fig. 1-12 Properties of Water Polarity asymmetric charge distribution makes molecule dipolar (polar) O atom δ, H atom δ+ strong ionic character to O-H bond Hydrogen bonding Water molecule bent: In how many hydrogen bonds can 1 H 2 O molecule participate? and Properties of Water 11
H 2 O H-bonding in ice Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig. 2-2 Solvent Properties of Water Excellent solvent for: Ions/charged groups Neutral polar compounds, e.g. sugars: highly solvated (H-bonds to solvent HOH) and Properties of Water 12
Solvent Properties of Water, continued Poor solvent for hydrophobic groups - fatty acid alkyl tail Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig. 2-7a Fatty acid: example of an amphipathic (amphiphilic) molecule Ionization Properties of H 2 O Review from general chemistry -- see Gen Chem review material for details. notes posted, covered in review session given at 2 different times, duplicate sessions to permit more students to attend (4:00-5:00 pm Thurs. and Fri. p.m., first week of classes) General chemistry is a prerequisite for biochem, and you need to understand it -- review it on your own and come to review session. General concepts of chemical equilibrium and equilibrium constants Importance of H + (proton) concentration in cells and in extracellular media State of ionization of weakly acidic groups on biomolecules important to structure and function Titration curves Buffers and Properties of Water 13
Ionization Properties of H 2 O - Summary H 2 O and acids in aqueous solution dissociate to yield protons (H + ) (hydrated, forming H 3 O + etc.) Proton concentrations often expressed on log 10 scale as ph: ph = log[h + ] Tendency of Bronsted acid to donate proton to H 2 O (dissociate the proton) is described by its equilibrium acid dissoc. constant K a, i.e. by its pk a = log K a. pk a = log K a pk a values measured experimentally by titration curves as the ph at half equivalence points Relationship between ph, pk a, and ratio of conjugate base/conjugate acid described by the Henderson-Hasselbalch Equation: Buffers Homeostasis: maintenance of constant conditions in internal environment Fluids in living systems -- ph is regulated, almost constant ph regulated by buffer systems Buffer: aqueous system that resists changes in ph when small amounts of acid or base are added Buffer system: aqueous solution of a weak acid and its conjugate base Buffer range of a weak acid: ph values near its pk a, about ±1 ph unit from pk a (Maxium buffering capacity is at the pk a.) Equilibrium acid dissocation reaction (remember Le Chatelier s Principle, the law of mass action ): HA <==> H + + A The higher the [H + ] (the lower the ph), the more equilib. shifts to left. The lower the [H + ] (the higher the ph), the more equilib. shifts to right. Exact ratio of base/acid (A /HA) depends on Henderson-Hasselbalch Eq: When ph = pk a, [A ] = [HA], i.e., [base] = [acid] and Properties of Water 14
2 Physiologically Important Buffer Systems Intracellular: Phosphate species Inorganic phosphate (phosphoric acid) Organic phosphates, e.g., phosphomonoesters Extracellular (blood plasma of mammals): carbonic acid / bicarbonate buffer system pk a ~6.1 and Properties of Water 15
1. Physiologically, how would a mammal deal with acidosis (blood ph, [H + ] ) in the short term? 2. Physiologically, how would a mammal deal with alkalosis (blood ph ; [H + ] ) in the short term? and Properties of Water 16