Generalities Thermodynamics Andy Howard Biochemistry Fall 2013 IIT
Generalities; Thermodynamics Andy Howard Biochemistry, Fall 2013 IIT 08/23/2012 Generalities; Thermodynamics 1
Plans l l l l Classes of Macromolecules Water Catalysis Energetics Regulation Molecular biology Evolution Thermodynamics 08/23/2012 Thermodynamic properties l Thermo units l Entropy l – Definitions – Solvation – Surfaces Free Energy l Solving Thermo problems l Generalities; Thermodynamics p. 2 of 42
Biological macromolecules l Most big biological molecules are polymers, i. e. molecules made up of large numbers of relatively simple building blocks. l Cobalamin is the biggest nonpolymeric biomolecule I can think of (MW 1356 Da) 08/23/2012 Generalities; Thermodynamics Structure courtesy Wikimedia p. 3 of 42
Categories of biological polymers Biopolymers are assembled by adding one monomer at a time to the growing chain by dehydration l Proteins l Nucleic acids l Polysaccharides. . Only the polysaccharides are typically branched; the others are linear 08/23/2012 Generalities; Thermodynamics p. 4 of 42
Polymers and oligomers l These are distinguished only by the number of building-blocks contained within the multimer l Oligomers: typically < 50 building blocks l Polymers 50 building blocks. 08/23/2012 Generalities; Thermodynamics p. 5 of 42
Categories of biopolymers Category # monomers <mol wt/ monomer> # monomers Branching? Protein 20 110 65 -5000 no RNA 4 -10 220 -400 50 -15 K no DNA 4 200 -400 50 -106 no Polysaccharide ~10 162 2 -105 Sometimes 08/23/2012 Generalities; Thermodynamics p. 6 of 42
Water: a complex substance Oxygen atom is covalently bonded to 2 hydrogens l Single bond character of these bonds means the H-O-H bond angle is close to 109. 5º = acos(-1/3): actually more like 104. 5º l This contrasts with O=C=O (angle=180º) or urea ((NH 2)2 -C=O) (angles=120º) l Two lone pairs available per oxygen: these are available as H-bond acceptors l 08/23/2012 Generalities; Thermodynamics p. 7 of 42
Water is polar l Charge is somewhat unequally shared l Small positive charge on H’s (d+); small negative charge on O (2 d-) (Why? ) l A water molecule will orient itself to align partial negative charge on one molecule close to partial positive charges on another. l Hydrogen bonds are involved in this. 08/23/2012 Generalities; Thermodynamics p. 8 of 42
Liquid water is mobile l The hydrogen-bond networks created among water molecules change constantly on a sub-picosecond time scale l At any moment the H-bonds look like those in crystalline ice l Solutes disrupt the H-bond networks 08/23/2012 Generalities; Thermodynamics p. 9 of 42
Water in reactions Water is a medium within which reactions occur; l But it also participates in reactions l Enzymes often function by making water oxygen atoms better nucleophiles or water H’s better electrophiles l Therefore water is a direct participant in reactions that wouldn’t work in a nonenzymatic lab setting! l 08/23/2012 Generalities; Thermodynamics p. 10 of 42
Water’s incompressibility l Water is nearly incompressible, i. e. its density is nearly independent of pressure l Density of ice is lower than that of water; otherwise, oceans would freeze from the bottom and (? ) prevent life l Maximum density appears at 3. 98ºC 08/23/2012 Generalities; Thermodynamics p. 11 of 42
Other physical properties of water l High specific heat, so it takes a lot of heat to change its temperature l High surface tension; that affects flow properties and the ability of organisms to live on water surfaces 08/23/2012 Generalities; Thermodynamics p. 12 of 42
Catalysis Free energy uncatalyzed R Reaction coordinate l Catalysis is the lowering of the activation energy barrier between reactants and products l How? – Physical surface on which reactants can be exposed to one another – Providing moieties that can temporarily participate in the reaction and be restored to their original state at the end 08/23/2012 P Generalities; Thermodynamics p. 13 of 42
Biological catalysts 1890’s: Emil Fischer realized that there had to be catalysts in biological systems l 1920’s: James Sumner said they were proteins l It took another 10 years for the whole community to accept that l It’s now known that RNA can be catalytic too: – Can catalyze modifications in itself – Catalyzes the key step in protein synthesis in the ribosome l 08/23/2012 Generalities; Thermodynamics p. 14 of 42
Energy in biological systems l We distinguish between thermodynamics and kinetics: l Thermodynamics characterizes the energy associated with equilibrium conditions in reactions l Kinetics describes the rate at which a reaction moves toward equilibrium 08/23/2012 Generalities; Thermodynamics p. 15 of 42
Thermodynamics l Equilibrium constant is a measure of the ratio of product concentrations to reactant concentrations at equilibrium l Free energy is a measure of the available energy in the products and reactants l They’re related by Go = -RT ln Keq 08/23/2012 Generalities; Thermodynamics p. 16 of 42
Kinetics l Rate of reaction is dependent on Kelvin temperature T and on activation barrier G‡ preventing conversion from one site to the other l Rate = Qexp(- G‡/RT) l Job of an enzyme is to reduce G‡ 08/23/2012 Generalities; Thermodynamics Svante Arrhenius p. 17 of 42
Regulation Biological reactions are regulated in the sense that they’re catalyzed by enzymes, so the presence or absence of the enzyme determines whether the reaction will proceed l The enzymes themselves are subject to extensive regulation so that the right reactions occur in the right places and times l 08/23/2012 Generalities; Thermodynamics p. 18 of 42
Typical enzymatic regulation Suppose enzymes are involved in converting A to B, B to C, C to D, and D to F. E is the enzyme that converts A to B: (E) A B C D F l In many instance F will inhibit (interfere) with the reaction that converts A to B by binding to a site on enzyme E so that it can’t bind A. l This feedback inhibition helps to prevent overproduction of F—homeostasis. l 08/23/2012 Generalities; Thermodynamics p. 19 of 42
Molecular biology This phrase means something much more specific than biochemistry: l It’s the chemistry of replication, transcription, and translation, i. e. , the ways that genes are reproduced and expressed. l Most of you have taken biology 214 or 515 or their equivalents; we’ll review some of the contents of that course here, mostly near the middle of the semester. l 08/23/2012 Generalities; Thermodynamics p. 20 of 42
The molecules of molecular biology Deoxyribonucleic acid: polymer; backbone is deoxyribose-phosphate; side chains are nitrogenous ring compounds l RNA: polymer; backbone is ribose-phosphate; side chains as above l Protein: polymer: backbone is NH-(CHR)-CO; side chains (R-groups) are 20 ribosomally encoded styles l 08/23/2012 Generalities; Thermodynamics p. 21 of 42
Steps in molecular biology: the Central Dogma DNA replication (makes accurate copy of existing double-stranded DNA prior to mitosis) l Transcription (RNA version of DNA message is created) l Translation (m. RNA copy of gene serves as template for making protein: 3 bases of RNA per amino acid of synthesized protein) l 08/23/2012 Generalities; Thermodynamics p. 22 of 42
Evolution and Taxonomy Traditional studies of interrelatedness of organisms focused on functional similarities l This enables production of phylogenetic trees l Molecular biology provides an alternative, possibly more quantitative, approach to phylogenetic treebuilding l More rigorous hypothesis-testing possible l 08/23/2012 Generalities; Thermodynamics p. 23 of 42
Quantitation Biochemistry is a quantitative science. l Results in biochemistry are rarely significant unless they can be couched in quantifiable terms. l Thermodynamic & kinetic behavior of biochemical systems must be described quantitatively. l Even the descriptive aspects of biochemistry, e. g. the compartmentalization of reactions and metabolites into cells and into particular parts of cells, must be characterized numerically. l 08/23/2012 Generalities; Thermodynamics p. 24 of 42
Mathematics in biochemistry Biochemistry is fundamentally an empirical discipline and is highly dependent on quantitative experiments l Many branches of mathematics are relevant to biochemical research l In this class we will rarely go beyond high school algebra (including logarithms and exponentials), but you’d better be comfortable with those l 08/23/2012 Generalities; Thermodynamics p. 25 of 42
Exponentials Many important biochemical equations are expressed in the form Y = ef(x) l … which can also be written Y = exp(f(x)) l The number e is the base of the natural logarithm system and is, very roughly, 2. 71828459045 l I. e. , it’s 2. 7 1828 45 90 45 l 08/23/2012 Generalities; Thermodynamics p. 26 of 42
Algebra of exponentials l l l Recognize that (e. A)(e. B) = e(A+B), or exp(A) exp(B) = exp(A+B) Similarly e. A/e. B = e(A-B) This becomes particularly useful when calculating ratios of similar quantities: Arrhenius relationship says k = Qe- G‡/RT Therefore the ratio of k values at two different temperatures is k 1/k 2 = e( G‡/R)(1/T 2 -1/T 1) 08/23/2012 Generalities; Thermodynamics p. 27 of 42
Logarithms l First developed as computational tools because they convert multiplication problems into addition problems l They have a fundamental connection with raising a value to a power: l Y = xa logx(Y) = a l In particular, Y = exp(a) = ea ln. Y = loge(Y) = a 08/23/2012 Generalities; Thermodynamics p. 28 of 42
Algebra of logarithms l l logv(A) = logu(A) / logu(v) logu(A/B) = logu(A) - logu(B) logu(AB) = Blogu(A) log 10(A) = ln(A) / ln(10) = ln(A) / 2. 30258509299 = 0. 4342944819 * ln(A) = log 10(A) / log 10 e = log 10(A) / 0. 4342944819 = 2. 30258509299 * log 10(A) 08/23/2012 Generalities; Thermodynamics p. 29 of 42
Energy in biological systems l We distinguish between thermodynamics and kinetics: l Thermodynamics characterizes the energy associated with equilibrium conditions in reactions l Kinetics describes the rate at which a reaction moves toward equilibrium 08/23/2012 Generalities; Thermodynamics p. 30 of 42
Thermodynamics l Equilibrium constant is a measure of the ratio of product concentrations to reactant concentrations at equilibrium l Free energy is a measure of the available energy in the products and reactants l They’re related by Go = -RT ln Keq 08/23/2012 Generalities; Thermodynamics p. 31 of 42
Thermodynamics! l Our one-semester biochem textbook puts this in the middle of chapter 10; Garrett & Grisham are smart enough to put it in the beginning. l You can tell which I prefer! 08/23/2012 Generalities; Thermodynamics p. 32 of 42
Why we care G Reaction Coord. Free energy is directly related to the equilibrium of a reaction l It doesn’t tell us how fast the system will come to equilibrium l Kinetics, and the way that enzymes influence kinetics, tell us about rates l Today we’ll focus on equilibrium energetics; we’ll call that thermodynamics l 08/23/2012 Generalities; Thermodynamics p. 33 of 42
… but first: i. Clicker questions! l 1. Which of the following statements is true? – (a) All enzymes are proteins. – (b) All proteins are enzymes. – (c) All viruses use RNA as their transmittable genetic material. – (d) None of the above. 08/23/2012 Generalities; Thermodynamics p. 34 of 42
i. Clicker question 2 l 2. Biopolymers are generally produced in reactions in which building blocks are added head to tail. Apart from the polymer, what is the most common product of these reactions? (a) Water (b) Ammonia (c) Carbon Dioxide (d) Glucose (e) None of the above. Polymerization doesn’t produce secondary products 08/23/2012 Generalities; Thermodynamics p. 35 of 42
i. Clicker question #3 l 3. Which type of biopolymer is sometimes branched? (a) DNA (b) Protein (c) Polysaccharide (d) RNA (e) They’re all branched. 08/23/2012 Generalities; Thermodynamics p. 36 of 42
i. Clicker question 4 l Free G Energy 4. The red curve represents the reaction pathway for an uncatalyzed reaction. Which one is the pathway for a catalyzed reaction? 08/23/2012 A D B C Reaction Coordinate Generalities; Thermodynamics p. 37 of 42
Laws of Thermodynamics l Traditionally four (0, 1, 2, 3) l Can be articulated in various ways l First law: The energy of an isolated system is constant. l Second law: Entropy of an isolated system increases. 08/23/2012 Generalities; Thermodynamics p. 38 of 42
What do we mean by systems, closed, open, and isolated? A system is the portion of the universe with which we’re concerned (e. g. , an organism or a rock or an ecosystem) l If it doesn’t exchange energy or matter with the outside, it’s isolated. l If it exchanges energy but not matter, it’s closed l If it exchanges energy & matter, it’s open l 08/23/2012 Generalities; Thermodynamics p. 39 of 42
That makes sense if… l l l Boltzmann It makes sense provided that we understand the words! Energy. Hmm. Capacity to do work. Entropy: Disorder. (Boltzmann): S = kln. W Isolated system: one in which energy and matter don’t enter or leave An organism is not an isolated system: so S can decrease within an organism! 08/23/2012 Generalities; Thermodynamics Gibbs p. 40 of 42
Enthalpy, H Closely related to energy: H = E + PV Kamerlingh l Therefore changes in H are: Onnes H = E + P V + V P l Most, but not all, biochemical systems have constant V, P: H = E l Related to amount of heat content in a system l 08/23/2012 Generalities; Thermodynamics p. 41 of 42
Kinds of thermodynamic properties Extensive properties: Thermodynamic properties that are directly related to the amount (e. g. mass, or # moles) of stuff present (e. g. E, H, S) l Intensive properties: not directly related to mass (e. g. P, T) l E, H, S are state variables; work, heat are not l 08/23/2012 Generalities; Thermodynamics p. 42 of 42
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