1. Generalities; Thermodynamics
Andy Howard
Introductory Biochemistry, Fall 2014 IIT
08/27/2014
Generalities; Thermodynamics

2. Generalities; Thermodynamics
Plans
Thermodynamics
Thermodynamic properties
Thermodynamic units
Generalities
Course Structure
Water
Catalysis
Energetics
Regulation
Molecular biology
Evolution
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Generalities; Thermodynamics

3. Generalities; Thermodynamics
Course structure
I teach biology 401 all semester; Prof. Nicholas Menhart teaches the follow-up course, biology 402, which focuses on specific metabolic systems
We will introduce general concepts of metabolism this semester without going into specific systems
We’ll spend a fair amount of time discussing techniques and analytical approaches, which will be instantiated in 402
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Generalities; Thermodynamics

4. Generalities; Thermodynamics
Examination plans
Two midterms (9/29, 11/3) plus a final on Monday 8 December from 8 to 10am
My exams will be closed-book, closed-notes exams; only approved calculators allowed
You’ll have a help-sheet for each of my exams
Gauge your memorization with the help-sheet before you: what’s on the help sheet doesn’t need to be memorized
My exams tend to be long but easy: budget your time carefully!
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Generalities; Thermodynamics

5. Generalities; Thermodynamics
Grading
I’m a moderately tough grader, but I do curve this course
Curving is relative to students over several years of performance, not just this year
The cutoff for an A is likely to be around an 82, but it’s uncertain
Homework, literature assignments, iClicker quizzes, and discussion-board participation count; see Blackboard site for details
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Generalities; Thermodynamics

6. Textbook and Lecture Notes
Required textbook: Garrett & Grisham, Biochemistry, 5th edition. It’s a detail-rich text and is clearly written.
Be prepared for the lecture notes themselves to evolve during the course; they’re all posted, but I will generally revise them the day that I deliver the lecture.
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Generalities; Thermodynamics

7. Generalities; Thermodynamics
Office Hours
Life Sciences Room 174
I should be available Monday and Wednesday from 10am to 1pm
If that doesn’t work, make an appointment: office , cell
The discussion board is another good way to reach me and the rest of the class as well!
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Generalities; Thermodynamics

8. Generalities; Thermodynamics
Assignments
Regular homework will be due weekly, generally on Fridays
But no assignment due this week
Literature assignments are due weekly on Tuesdays (except yesterday)
Specific readings already posted will be augmented but not deleted
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Generalities; Thermodynamics

9. Generalities; Thermodynamics
Lateness?
Regular homework:
No penalty if turned in by 24 h of deadline
Modest penalties if 1-7 days late
After 7 days the answer key will be posted, so no credit given after that
Literature assignments:
Half credit if turned in 1-7 days late
Limited credit later than that
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Generalities; Thermodynamics

10. Arrangements for exams
Live students should take the exams on the stated dates
Internet students should begin the midterms between 9am on the statutory date and 5pm on the day after
If you’re a non-local Internet student, you need to find a proctor well before 29 September!
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Generalities; Thermodynamics

11. Generalities; Thermodynamics
How exams work
Combination of multiple-choice, short answer, paragraph-answer, and computational problems
Only approved calculators will be permitted. NCEES list of calculators is the primary source; approval of any other calculator is my decision in advance.
Multiple-page help sheet will be available for each exam; in fact, the current drafts of the help-sheets are already on Blackboard
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Generalities; Thermodynamics

12. Other administrative stuff
Feel free to watch the Internet lectures even if you’re in the live class
But if you’re in the live section, I expect you to attend class
If you miss a live class that includes an iClicker quiz, you’ll get a zero on that iClicker quiz unless you’ve made arrangements in advance to compensate
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Generalities; Thermodynamics

13. Generalities; Thermodynamics
How do iClickers work?
You can either buy an iClicker from the IIT Bookstore or Amazon; or
You can purchase a smartphone app that mimics an iClicker
I’d prefer that you buy an actual iClicker because they’re more reliable
Bring it to class every day; I will bring a few extras each day, but don’t rely on that
me the 8-hex-digit number on the back; it’s the code that relates you to your answers.
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Generalities; Thermodynamics

14. Generalities; Thermodynamics
Special announcement
I am a cast member at the Bristol Renaissance Faire in Pleasant Prairie, WI, on Interstate 94, just north of the IL/WI border
This coming weekend is the final weekend of the Faire; it’s open Saturday, Sunday, and Monday, rather than just Sat & Sun
I invite any of you to attend at my expense
Just let me know by text message before 9am Saturday so I can buy the tickets for you
Tickets will be waiting at the Will Call window
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Generalities; Thermodynamics

15. Water: a complex substance
Oxygen atom is covalently bonded to 2 hydrogens
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
This contrasts with O=C=O (angle=180º) or urea ((NH2)2-C=O) (angles=120º)
Two lone pairs available per oxygen: these are available as H-bond acceptors
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Generalities; Thermodynamics

16. Generalities; Thermodynamics
Water is polar
Charge is somewhat unequally shared
Small positive charge on H’s (d+); small negative charge on O (2d-) (Why?)
A water molecule will orient itself to align partial negative charge on one molecule close to partial positive charges on another.
Hydrogen bonds are involved in this.
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Generalities; Thermodynamics

17. Generalities; Thermodynamics
Liquid water is mobile
The hydrogen-bond networks created among water molecules change constantly on a sub-picosecond time scale
At any moment the H-bonds look like those in crystalline ice
Solutes disrupt the H-bond networks
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Generalities; Thermodynamics

18. Generalities; Thermodynamics
Water in reactions
Water is a medium within which reactions occur;
But it also participates in reactions
Enzymes often function by making water oxygen atoms better nucleophiles or water H’s better electrophiles
Therefore water is a direct participant in reactions that wouldn’t work in a nonenzymatic lab setting!
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Generalities; Thermodynamics

19. Water’s incompressibility
Water is nearly incompressible, i.e. its density is nearly independent of pressure
Density of ice is lower than that of water; otherwise, oceans would freeze from the bottom and (?) prevent life
Maximum density appears at 3.98ºC
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Generalities; Thermodynamics

20. Other physical properties of water
High specific heat, so it takes a lot of heat to change its temperature
High surface tension; that affects flow properties and the ability of organisms to live on water surfaces
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21. Generalities; Thermodynamics
uncatalyzed
Catalysis
Free energy
catalyzed P R
Reaction coordinate
Catalysis is the lowering of the activation energy barrier between reactants and products
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
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Generalities; Thermodynamics

22. Generalities; Thermodynamics
Biological catalysts
1890’s: Emil Fischer realized that there had to be catalysts in biological systems
1920’s: James Sumner said they were proteins
It took another 10 years for the whole community to accept that
We now know: RNA can be catalytic too:
Can catalyze modifications in itself
Catalyzes the key step in protein synthesis in the ribosome
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Generalities; Thermodynamics

23. Energy in biological systems
We distinguish between thermodynamics and kinetics:
Thermodynamics characterizes the energy associated with equilibrium conditions in reactions
Kinetics describes the rate at which a reaction moves toward equilibrium
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Generalities; Thermodynamics

24. Generalities; Thermodynamics
Equilibrium constant is a measure of the ratio of product concentrations to reactant concentrations at equilibrium
Free energy is a measure of the available energy in the products and reactants
They’re related by DGo = -RT ln Keq
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Generalities; Thermodynamics

25. Generalities; Thermodynamics
Kinetics
Rate of reaction is dependent on Kelvin temperature T and on activation barrier DG‡ preventing conversion from one site to the other
Rate = Qexp(-DG‡/RT)
Job of an enzyme is to reduce DG‡
Svante Arrhenius
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Generalities; Thermodynamics

26. Generalities; Thermodynamics
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
The enzymes themselves are subject to extensive regulation so that the right reactions occur in the right places and times
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Generalities; Thermodynamics

27. 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
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.
This feedback inhibition helps to prevent overproduction of F—homeostasis.
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Generalities; Thermodynamics

28. Generalities; Thermodynamics
Molecular biology
This phrase means something much more specific than biochemistry:
It’s the chemistry of replication, transcription, and translation, i.e., the ways that genes are reproduced and expressed.
Most of you have taken biology 214 or 515 or their equivalents; we’ll review some of the contents of those courses here, mostly near the middle of the semester.
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Generalities; Thermodynamics

29. The molecules of molecular biology
Deoxyribonucleic acid: polymer; backbone is deoxyribose-phosphate; side chains are nitrogenous ring compounds
RNA: polymer; backbone is ribose-phosphate; side chains as above
Protein: polymer: backbone is NH-(CHR)-CO; side chains (R-groups) are 20 ribosomally encoded styles
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Generalities; Thermodynamics

30. Steps in molecular biology: the Central Dogma
DNA replication (makes accurate copy of existing double-stranded DNA prior to mitosis)
Transcription (RNA version of DNA message is created)
Translation (mRNA copy of gene serves as template for making protein: 3 bases of RNA per amino acid of synthesized protein)
Fundamental insight of the late 20th century is that RNA is involved in many processes in addition to translation.
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Generalities; Thermodynamics

31. Evolution and Taxonomy
Traditional studies of interrelatedness of organisms focused on functional similarities
This enables production of phylogenetic trees
Molecular biology provides an alternative, possibly more quantitative, approach to phylogenetic tree-building
More rigorous hypothesis-testing possible
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32. Generalities; Thermodynamics
Quantitation
Biochemistry is a quantitative science.
Results in biochemistry are rarely significant unless they can be couched in quantifiable terms.
Thermodynamic & kinetic behavior of biochemical systems must be described quantitatively.
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.
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Generalities; Thermodynamics

33. Mathematics in biochemistry
Biochemistry is fundamentally an empirical discipline and is highly dependent on quantitative experiments
Many branches of mathematics are relevant to biochemical research
In this class we will rarely go beyond high school algebra (including logarithms and exponentials), but you’d better be comfortable with those
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Generalities; Thermodynamics

34. Generalities; Thermodynamics
Exponentials
Many important biochemical equations are expressed in the form Y = ef(x)
… which can also be written Y = exp(f(x))
The number e is the base of the natural logarithm system and is, very roughly,
I.e., it’s
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35. Algebra of exponentials
Recognize that (eA)(eB) = e(A+B), or exp(A) exp(B) = exp(A+B)
Similarly eA/eB = 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
k1/k2 = e(G‡/R)(1/T2-1/T1)
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Generalities; Thermodynamics

36. Generalities; Thermodynamics
Logarithms
First developed as computational tools because they convert multiplication problems into addition problems
They have a fundamental connection with raising a value to a power:
Y = xa  logx(Y) = a
In particular, Y = exp(a) = ea lnY = loge(Y) = a
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Generalities; Thermodynamics

37. Generalities; Thermodynamics
Algebra of logarithms
logv(A) = logu(A) / logu(v)
logu(A/B) = logu(A) - logu(B)
logu(AB) = Blogu(A)
log10(A) = ln(A) / ln(10) = ln(A) / = * ln(A)
ln(A) = log10(A) / log10e = log10(A) / = * log10(A)
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Generalities; Thermodynamics

38. Energy in biological systems
We distinguish between thermodynamics and kinetics:
Thermodynamics characterizes the energy associated with equilibrium conditions in reactions
Kinetics describes the rate at which a reaction moves toward equilibrium
08/27/2014
Generalities; Thermodynamics

39. Generalities; Thermodynamics
Equilibrium constant is a measure of the ratio of product concentrations to reactant concentrations at equilibrium
Free energy is a measure of the available energy in the products and reactants
They’re related by DGo = -RT ln Keq
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Generalities; Thermodynamics

40. Generalities; Thermodynamics
Our one-semester biochemistry textbook puts this topic in the middle of chapter 10; Garrett & Grisham are smart enough to put it in the beginning.
You can tell which I prefer!
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Generalities; Thermodynamics

41. Generalities; Thermodynamics
Why we care G
Reaction Coord.
Free energy is directly related to the equilibrium of a reaction
It doesn’t tell us how fast the system will come to equilibrium
Kinetics, and the way that enzymes influence kinetics, tell us about rates
Today we’ll focus on equilibrium energetics; we’ll call that thermodynamics
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Generalities; Thermodynamics

42. … but first: iClicker questions!
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.
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43. Generalities; Thermodynamics
iClicker question 2
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
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44. Generalities; Thermodynamics
iClicker question #3
3. Which type of biopolymer is sometimes branched? (a) DNA (b) Protein (c) Polysaccharide (d) RNA (e) They’re all branched.
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45. Generalities; Thermodynamics
iClicker question 4
Free Energy
4. The red curve represents the reaction pathway for an uncatalyzed reaction. Which one is the pathway for a catalyzed reaction? G A D B C
Reaction Coordinate
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Generalities; Thermodynamics

46. Laws of Thermodynamics
Traditionally four (0, 1, 2, 3)
Can be articulated in various ways
First law: The energy of an isolated system is constant.
Second law: Entropy of an isolated system increases.
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47. 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)
If it doesn’t exchange energy or matter with the outside, it’s isolated.
If it exchanges energy but not matter, it’s closed
If it exchanges energy & matter, it’s open
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48. Generalities; Thermodynamics
That makes sense if…
Boltzmann
Gibbs
It makes sense provided that we understand the words!
Energy. Hmm. Capacity to do work.
Entropy: Disorder. (Boltzmann): S = klnW
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!
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Generalities; Thermodynamics

49. Generalities; Thermodynamics
Enthalpy, H
Closely related to energy: H = E + PV
Therefore changes in H are: H = E + PV + VP
Most, but not all, biochemical systems have constant V, P: H = E
Related to amount of heat content in a system
Kamerlingh Onnes
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Generalities; Thermodynamics

50. 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)
Intensive properties: not directly related to mass (e.g. P, T)
E, H, S are state variables; work, heat are not
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Generalities; Thermodynamics

51. Generalities; Thermodynamics
Units
Energy unit: Joule (kg m2 s-2)
1 kJ/mol = 103J/(6.022*1023) = 1.661*10-21 J
1 cal = J: so 1 kcal/mol = *10-21 J
1 eV = 1 e * J/Coulomb = 1.602*10-19 C * 1 J/C = 1.602*10-19 J = 96.4 kJ/mol = 23.1 kcal/mol
James Prescott Joule
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Generalities; Thermodynamics