1. Introduction to Biochemistry
Andy Howard
Biochemistry, Fall 2010 IIT
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Biochemistry: Introduction

2. Biochemistry: Introduction
What is biochemistry?
By the end of this course you should be able to construct your own definition; but for now:
Biochemistry is the study of chemical reactions in living tissue.
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Biochemistry: Introduction

3. Biochemistry: Introduction
Plans
Classes of small molecules
Classes of macromolecules
Water
Catalysis
Energetics
Regulation
Molecular biology
Evolution
What is biochemistry?
Cells
Cell components
Organic and biochemistry
Concepts from organic chemistry to remember
Small molecules and macromolecules
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Biochemistry: Introduction

4. Biochemistry: Introduction
What will we study?
Biochemistry is the study of chemical reactions in living tissue, both within cells and in intercellular media.
As such, it concerns itself with a variety of specific topics:
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Biochemistry: Introduction

5. Topics in biochemistry
What reactions occur;
The equilibrium energetics and kinetics of those reactions;
How the reactions are controlled, at the chemical and cellular or organellar levels;
How the reactions are organized to enable biological function within the cell and in tissues and organisms.
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Biochemistry: Introduction

6. Organic and biological chemistry
Most molecules in living things (other than H2O, O2, and CO2) contain C-C or C-H bonds, so biochemistry depends heavily on organic chemistry
But the range of organic reactions that occur in biological systems is fairly limited compared to the full range of organic reactions:
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Biochemistry: Introduction

7. Why we use only a subset of organic chemistry in biochemistry
Biochemical reactions are almost always aqueous.
They occur within a narrow temperature and pressure range.
They occur within narrowly buffered pH ranges.
Many of the complex reaction mechanisms discovered and exploited by organic chemists since the 1860's have no counterparts in the biochemical universe.
Frederich Wöhler
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Biochemistry: Introduction

8. Biochemistry: Introduction
Cells
Most biochemical reactions (but not all!) take place within semi-independent biological entities known as cells
Cells in general contain replicative and protein-synthetic machinery in order to reproduce and survive
They often exchange nutrients and information with other cells
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Biochemistry: Introduction

9. Biochemistry: Introduction
Cell components
Cells are separated from their environments via a selectively porous membrane
Individual components (often called organelles) within the cell may also have membranes separating them from the bulk cytosol and from one another
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Biochemistry: Introduction

10. Eukaryotes and prokaryotes
The lowest-level distinction among organisms is on the basis of whether their cells have defined nuclei or not
Cells with nuclei are eukaryotic
Cells without nuclei are prokaryotic
Eubacteria and archaea are prokaryotic
Other organisms (including some unicellular ones!) are eukaryotic
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Biochemistry: Introduction

11. Eukaryotic organelles I
Nucleus: contains genetic information; site for replication and transcription
Endoplasmic reticulum: site for protein synthesis and protein processing
Ribosome: protein-synthetic machine
Golgi apparatus: site for packaging proteins for secretion and delivery
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Biochemistry: Introduction

12. Eukaryotic organelles II
Mitochondrion: site for most energy-producing reactions
Lysosome: digests materials during endocytosis and cellular degradation
Peroxisome: site for oxidation of some nutrients and detoxification of the H2O2 created thereby
Cytoskeleton: network of filaments that define the shape and mobility of a cell
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Biochemistry: Introduction

13. Eukaryotic organelles III
Chloroplast: site for most photosynthetic reactions
Vacuoles: sacs for water or other nutrients
Cell wall: bacterial or plant component outside cell membrane that provides rigidity and protection against osmotic shock
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Biochemistry: Introduction

14. Biochemistry: Introduction
Molecular machines
Cells contain components featuring enzyme-driven molecular machines that accomplish specific tasks
Usually too small and too internalized within cells or organelles to be considered as organelles themselves, but they’re still important
Examples: proteasome, spliceosomes, fatty acid synthases
Ribosomes are borderline between organelles and molecular machines
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Biochemistry: Introduction

15. Concepts from organic chemistry
There are some elements of organic chemistry that you should have clear in your minds.
All of these are concepts with significance outside of biochemistry, but they do play important roles in biochemistry.
If any of these concepts is less than thoroughly familiar, please review it:
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Biochemistry: Introduction

16. Biochemistry: Introduction
Organic concepts I
Image courtesy Michigan State U.
Covalent bond: A strong attractive interaction between neighboring atoms in which a pair of electrons is roughly equally shared between the two atoms.
Covalent bonds may be single bonds, in which one pair of electrons is shared; double bonds, which involve two pairs of electrons; or triple bonds, which involve three pairs (see above).
Single bonds do not restrict the rotation of other substituents around the bond; double and triple bonds do.
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Biochemistry: Introduction

17. Biochemistry: Introduction
Organic concepts II
Ionic bond: a strong attractive interaction between atoms in which one atom or group is positively charged, and another is negatively charged.
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Biochemistry: Introduction

18. Biochemistry: Introduction
Organic concepts III
Hydrogen bond: A weak attractive interaction between neighboring atoms in which a hydrogen atom carrying a slight, partial positive charge shares that positive charge with a neighboring electronegative atom.
The non-hydrogen atom to which the hydrogen is covalently bonded is called the hydrogen-bond donor;
the neighboring atom that takes on a bit of the charge is called the hydrogen-bond acceptor
Cartoon courtesy CUNY Brooklyn
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Biochemistry: Introduction

19. Biochemistry: Introduction
Organic concepts IV
Van der Waals interaction: A weak attractive interaction between nonpolar atoms, arising from transient induced dipoles in the two atoms.
Image courtesy Columbia U. Biology Dept.
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Biochemistry: Introduction

20. Biochemistry: Introduction
Organic Concepts V
Chirality: The property of a molecule under which it cannot be superimposed upon its mirror image.
Image courtesy DRECAM, France
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Biochemistry: Introduction

21. Biochemistry: Introduction
Organic Concepts VI
acetone
propen-2-ol
Tautomerization: The interconversion of two covalently different forms of a molecule via a unimolecular reaction that proceeds with a low activation energy. The two forms of the molecule are known as tautomers: because of the low activation barrier between the two forms, we will typically find both species present.
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Biochemistry: Introduction

22. Biochemistry: Introduction
Organic Concepts VII
Nucleophilic substitution: a reaction in which an electron-rich (nucleophilic) molecule attacks an electron-poor (electrophilic) molecule and replaces group or atom within the attacked species.
The displaced group is known as a leaving group.
This is one of several types of substitution reactions, and it occurs constantly in biological systems.
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Biochemistry: Introduction

23. Biochemistry: Introduction
Organic Concepts VIII
Polymerization: creation of large molecules by sequential addition of simple building blocks
often by dehydration, i.e., the elimination of water from two species to form a larger one: R1-O-H + HO-R2-X-H  R1-X-R2-OH + H2O
The product here can then react with HO-R3-X-H to form R1-X-R2-X-R3-OH with elimination of another water molecule, and so on.
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Biochemistry: Introduction

24. Biochemistry: Introduction
Organic Concepts IX
Equilibrium: in the context of a chemical reaction, the state in which the concentrations of reactants and products are no longer changing with time because the rate of reaction in one direction is equal to the rate in the opposite direction.
Kinetics: the study of the rates at which reactions proceed.
Conventionally, we use the term thermodynamics to describe our understanding of the energetics of equilibrium systems
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Biochemistry: Introduction

25. Biochemistry: Introduction
Organic Concepts X
Catalysis: the lowering of the energetic barrier between substrates and products in a reaction by the participation of a substance that ultimately is unchanged by the reaction
It is crucial to recognize that catalysts (chemical agents that perform catalysis) do not change the equilibrium position of the reactions in which they participate:
they only change the rates (the kinetics) of the reactions they catalyze.
Zwitterion: a compound containing both a positive and a negative charge
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Biochemistry: Introduction

26. Classes of small molecules
Small molecules other than water make up a small percentage of a cell's mass, but small molecules have significant roles in the cell, both on their own and as building blocks of macromolecules. The classes of small molecules that play significant roles in biology are listed below. In this list, "soluble" means "water-soluble".
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Biochemistry: Introduction

27. Biological small molecules I
Water: Hydrogen hydroxide. In liquid form in biological systems. See below.
Lipids: Hydrophobic molecules, containing either alkyl chains or fused-ring structures. A biological lipid usually contains at least one highly hydrophobic moeity.
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Biochemistry: Introduction

28. Biological small molecules II
Carbohydrates: Polyhydroxylated compounds for which the building blocks are highly soluble.
The typical molecular formula for the monomeric forms of these compounds is (CH2O)n, where 3 < n < 9,
but usually n = 3, 5 or 6.
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Biochemistry: Introduction

29. Biological small molecules III
Amino acids: Compounds containing an amine (NH3+) group and a carboxyl (COO-) group.
The most important biological amino acids are a-amino acids, in which the amine group and the carboxyl group are separated by one carbon, and that intervening carbon has a hydrogen attached to it. Thus the general formula for an a-amino acid is
H3N+ - CHR - COO-
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Biochemistry: Introduction

30. Biological small molecules IV
Nucleic acids: Soluble compounds that include a nitrogen-containing ring system.
The ring systems are derived either from purine or pyrimidine.
The most important biological nucleic acids are those in which the ring system is covalently attached to a five-carbon sugar, ribose, usually with a phosphate group attached to the same ribose ring.
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Biochemistry: Introduction

31. Biochemistry: Introduction
Small molecules V
Inorganic ions: Ionic species containing no carbon but containing one or more atoms and at least one net charge.
Ions of biological significance include Cl-, Na+, K+, Mg+2, Mn+2, I-, Ca+2, PO4-3, SO4-2, NO3-, NO2-, and NH4+.
Phosphate (PO4-3) is often found in partially protonated forms HPO4-2 and H2PO4-
Ammonium ions occasionally appear as neutral ammonia (NH3), particularly at higher pH values
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Biochemistry: Introduction

32. Biological Small Molecules VI
Cofactors: This is a catchall category for organic small molecules that serve in some functional role in biological organisms. Many are vitamins or are derived from vitamins; a vitamin is defined as an organic molecule that is necessary in small quantities for metabolism but cannot be synthesized by the organism. Thus the same compound may be a vitamin for one organism and not for another.
Ascorbate (vitamin C) is a vitamin for humans and guinea pigs but not for most other mammals.
Cofactors often end up as prosthetic groups, covalently or noncovalently attached to proteins and involved in those proteins' functions.
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Biochemistry: Introduction

33. Biological macromolecules
Most big biological molecules are polymers, i.e. molecules made up of large numbers of relatively simple building blocks.
Cobalamin is the biggest nonpolymeric biomolecule I can think of (MW 1356 Da)
Structure courtesy Wikimedia
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Biochemistry: Introduction

34. Categories of biological polymers
Proteins
Nucleic acids
Polysaccharides
Lipids (sort of):
2-3 chains of aliphatics attached to a polar head group, often built on glycerol
Aliphatic chains are usually C’s
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Biochemistry: Introduction

35. Polymers and oligomers
These are distinguished only by the number of building-blocks contained within the multimer
Oligomers: typically < 50 building blocks
Polymers  50 building blocks.
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Biochemistry: Introduction

36. Categories of biopolymers
Category
# mono-mers
<mol wt/ monomer>
Branch-ing?
Protein 20
110 no
RNA
4-10
50-15K
DNA 4
50-106
Polysac-charide
~10
180
2-105
Some- times
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Biochemistry: Introduction

37. 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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38. Biochemistry: Introduction
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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39. Biochemistry: Introduction
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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Biochemistry: Introduction

40. 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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Biochemistry: Introduction

41. Biochemistry: Introduction
Course structure
I teach biology 401 all semester; Prof. Nicholas Menhart teaches the followup 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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42. Biochemistry: Introduction
Examination plans
Two midterms (9/24, 10/29) plus a final
My exams will be closed-book, closed-notes exams. Calculators are not 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!
Final exam date will be set by Registrar soon
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Biochemistry: Introduction

43. Biochemistry: Introduction
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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Biochemistry: Introduction

44. Textbook and Lecture Notes
Required textbook: Garrett & Grisham, Biochemistry, either expanded 3rd ed. or 4th ed. It’s a detail-rich text and is clearly written.
You may wish to examine Horton, Principles of Biochemistry, which is somewhat shorter
Most of my lectures are derived from G&G, but I’ll often give cross references to Horton
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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Biochemistry: Introduction

45. Biochemistry: Introduction
Office Hours
Life Sciences Room 174
I should be available 3:30pm-6pm Tuesdays and Thursdays and often from 11am to 1pm as well
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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Biochemistry: Introduction

46. Biochemistry: Introduction
Assignments
Regular homeworks will be due weekly, generally on Fridays
But no assignment due this week
Literature assignments are due weekly on Tuesdays (except this one)
Specific readings already posted will be augmented but not deleted
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47. Biochemistry: Introduction
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
No credit later than that
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Biochemistry: Introduction

48. Arrangements for exams
Live students should take the exams on the stated dates—Thursday 9/23 and Tuesday 10/26
Internet & TV students should begin the midterms between 9am on the statutory Thursday and 5pm on Friday
If you’re a non-local Internet student, you need to find a proctor well before 23 Sep!
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49. Biochemistry: Introduction
How exams work
Combination of multiple-choice, short answer, paragraph-answer, and computational problems
No electronic devices of any kind allowed (you may need to review long division!)
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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Biochemistry: Introduction

50. Other administrative stuff
We may be moving to the Idea Shop so that you can use iPads down there
I’ll tell you that by Thursday’s class
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
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Biochemistry: Introduction