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 in Gen Chem Review.pdf (see Lecture Notes page) an elementary explanation of logarithms (Lec. Notes page). A very well done animation on the life of a cell everyone should watch: http://multimedia.mcb.harvard.edu/anim_innerlife.html Nelson & Cox, Lehninger Principles of Biochemistry, Fig. 2-7b 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. 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 ionization properties of weak acids/bases crucial to structures and functions of biomolecules ph determines state of ionization of biomolecular weak acids and bases. Buffers (intracellular and extracellular) Bacterial Cells REVIEW OF CELL STRUCTURES Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig.1-6 Properties of Water 2
Eukaryotic Cells Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig.1-7a Eukaryotic Cells Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig.1-7b Properties of Water 3
Review of Functional Groups in Biomolecules Review of Important Functional Groups in Biomolecules Properties of Water 4
Review of Condensation and Hydrolysis Reactions 1. Esters 2. Amides Properties of Water 5
3. Anhydrides Biochemistry: the chemical nature of life = the relationship between structure and function! You Say You Want a Revolution? : Metabolic: 50 s 80 s via radioisotopes Structural: 60 s present via X-ray crystallography and electron microsopy Molecular biology: 80 s present allows for site specific mutagenesis of proteins Genomic: 2000 Human Genome solved (24,000 genes for 800,000 1,000,000 proteins Proteomic: 2000 present via advances in mass spectrometry and computer technology Dawning of the Age of Systems Biology (i.e., putting it all together) Properties of Water 6
As of May 2010: Genomes solved Protein structures determined: 65,260 Things move fast in this business The Central Dogma: transcription DNA: 4 bases (A,T,C,G) mrna translation Proteins from 20 naturally occurring amino acids Function! Properties of Water 7
Biochemistry is based on four fundamental concepts Space (structure, proximity) Time (dynamic interacting processes) Bonds/Energy (the reversal of disorder): Thermodynamics Organic chemistry(a bit of inorganic): C, S, O, N, P, Fe, Cu, Zn, Mo SPACE (1 A {Angstrom} = 10-10 m=01nm) 0.1 Bonds: 1.5-3.0 A Molecules: 5-100 A Aggregates: 100-1000 A Cells: 10 4-10 5 A TIME Photosynthesis/vision: femto (10-15 ) to pico (10-12 ) seconds Protein motion: nano (10-9 ) to seconds Enzyme catalysis: micro (10-6 ) to seconds Cell division: 10 3 to 10 5 seconds Your life years Chemical Bonds/Interactions in Biomolecules Covalent bonds: single (356 kj/mol) & double (730) 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 ) 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). Properties of Water 8
Weak individually; collectively quite considerable! from Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed.) Ionic Interactions (charge-charge interactions = salt bridges): electrostatic attraction or repulsion between charged groups (-6 kj/mol in H 2 O; -231 in hexane) Coulomb s Law: E = Energy of interaction q s = charges (+/-, +/+, or -/-) 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 Properties of Water 9
Hydrogen Bonds H-bond Donor H-bond Acceptor (4 20 kj/mol) N---H ----------> : N O---H ----------> : O Electrostatic in nature. Effect of polarity of solvent on dielectric constant (D). Becomes significant ifi when H-bond is buried in non-polar protein interior. Strict distance dependence: 1.5 2.6 A (H O,N) 2.4-3.5 A (N O) Beyond these distances, H-bonds do not form. H-bonds cont d The energy of the H-bond is very dependent on orientation of the three atoms involved. Properties of Water 10
van der Waals Interactions (2 4 kj/mol) 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 Energy drops off by 1/r 6 (very dramatic) Berg et al., Fig. 1.10 Properties of Water 11
Bonding Characteristics Energy (kj/mol) Distance (A) Covalent 356 (single) 154 1.54 CC C-C 730 (double) 1.34 C=C Ionic -6 (@3.4 A;H 2 O) -231 (3.4 A;hexane) E drops off 1/r 2 Variable H-bond* 4 20 1.5 2.6 H->O 24 2.4 35 3.5 N>O N->O van der Waals* 2-4 per atom pair E drops off 1/r 6 4-5 * Individually very weak contribution, collectively enormous! Thermodynamics Biology depends on the laws of thermodynamics: the creation of order (life) from disorder (the universe). 1. First Law: The total energy of the SYSTEM and its SURROUNDINGS are CONSTANT. 2. Second Law: The total entropy of the SYSTEM and its SURROUNDINGS always increases for a spontaneous process. Increased entropy = death in the bio-world. Thus, nature favors disorder, life is the result of order. G = H T S = -RT lnk eq At Equilibrium is a very important concept! Properties of Water 12
Hydrophobic "Interactions" hydrophobic effect, the "oil drop" effect Nonpolar molecules (the system) cannot interact with H 2 O (the surroundings) by H-bonds or ionic interactions. Nonpolar molecule forces water to organize itself, decreasing entropy of H 2 O. In order to increase total entropy, water forces nonpolar molecules to interact with each other (decreasing system s entropy but increasing surrounding s entropy). Results in " hydrophobic or nonpolar interactions, which are entropically driven. Berg et al. Fig. 1-12 Properties of Water Polarity asymmetric charge distribution makes molecule dipolar (polar) Oatom, Hatom + strong ionic character to O-H bond Hydrogen bonding Water molecule bent: In how many hydrogen bonds can 1 H 2O molecule participate? p Properties of Water 13
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) Properties of Water 14
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 Gen Chem Review (Yes! You have to know how to use that stuff) Review from general chemistry -- see Gen Chem review material for details. Review notes posted, will be covered in review session tomorrow. General chemistry is a prerequisite for biochem, and you need to understand it -- review it on your own and/or 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 Properties of Water 15
Ionization Properties of H 2 O 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. Note: p(anything) = log (anything) 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 (Maximum 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 h 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] =? Properties of Water 16
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 Properties of Water 17
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? Learning Objectives and Review Material 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? Properties of Water 18
Learning Objectives and Review, 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 and Review, 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: 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. Properties of Water 19