Introduction to Biochemistry

1. Introduction to Biochemistry Andy Howard Biochemistry Lectures, Spring 201915 January 2019, Illinois Tech

2. 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. Biochemistry: Introduction

3. Plans • Course structure • What is biochemistry? • Cells • Organic and biochemistry • Small molecules & macromolecules Biochemistry: Introduction

4. How this course will operate Grading and other policies are set forth in the syllabus, which is on Blackboard Syllabus may be revised during the semester: I’ll let you know if it is. I’ll go slowly through concepts but rapidly through facts Next few slides will summarize what you’ll find on that syllabus Biochemistry: Introduction

5. Course objectives I • By the end of this course, each student should be able to: • Recognize and draw the structures of about 35 organic molecules of interest to biochemistry and explain their significance in metabolism; • Explain the role of thermodynamics and kinetics in biology Biochemistry: Introduction

6. Course objectives II • Characterize the role of enzymes and cofactors in biological systems, the mechanisms by which enzymes operate, and their sensitivity to regulation; • Characterize proteins, carbohydrates, and fats, and their roles in biological function; • Recognize the roles of deoxyribonucleic acid and ribonucleic acid in inheritance, replication, transcription, and translation; Biochemistry: Introduction

7. Course objectives III • Become familiar with some of the experimental tools used in biochemistry and molecular biology; • Summarize the synthetic & degradative pathways for carbohydrates, fats, proteins, and nucleic acids, and the biological significance of those pathways. Biochemistry: Introduction

8. How does this course fit in? Prerequisites: organic chem and a freshman biology course Chem 239 is helpful but not absolutely required This course provides preparation for almost any area of biochemistry, molecular biology, or biophysics Not part of biology majors’ course list, so it’s primarily designed for UGs in BME, ChBE, Chem Biochemistry: Introduction

9. What we’ll be doing Live section meets in Wishnick 115 on Tuesdays and Thursdays beginning 15 January and ending Thursday 3 May, from 3:15pm to 4:55pm First & Third midterms will be in that room too Second midterm will be a timed take-home Final exam will probably be in Hermann Expo Text: Campbell, Farrell, & McDougal, Biochemistry, 9th Edition, with accompanying OWLv2 study aids Biochemistry: Introduction

10. Grading breakdown (live section) Biochemistry: Introduction

11. How the exams will work I • First midterm & third midterm (Wishnick 115): • I supply a help-sheet (2-5 pages) • Use an approved calculator but no other electronic devices • 75 minutes • Final exam: 120 minutes, same rules, in Hermann • 2nd midterm: timed take-home on Blackboard;75 minutes • Careful proctoring: cheating will not be tolerated Biochemistry: Introduction

12. How exams work: II • Combination: multiple-choice, short answer, paragraph-answer, and computational problems • Only approved calculators will be permitted. NCEES list of calculatorsis primary source; approval of any other calculator is my decision in advance. • Multiple-page help sheet available for each exam; current drafts of help-sheets already on Blackboard • Don’t turn the help-sheets in! Keep them! Biochemistry: Introduction

13. Arrangements for exams • Students should expect to take the exams on the stated dates • If there are insoluble problems with the stated dates, discuss them with me. • Online students: see next slide Biochemistry: Introduction

14. Online students First & third midterms: take these exams between 9am Monday and 5pm Tuesday of the week when the live-section students take the exams 2nd midterm: identical to live section Final exam: like 1st & 3rd midterms Biochemistry: Introduction

15. Grading • I’m a moderately tough grader, but I do curve this course • I do not assign letter grades to individual assignments or midterms • 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 Biochemistry: Introduction

16. Lecture Notes • 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. • As mentioned earlier, I’ll go through concepts slowly; I’ll go through facts quickly. Biochemistry: Introduction

17. Office Hours • RAPSC Room 182 • Tuesday, Thursday, Friday 10am-noon • If that doesn’t work, make an appointment:howard@iit.eduoffice 312-567-5881, cell 773-368-5067 • The discussion board is another good way to reach me and the rest of the class as well! Biochemistry: Introduction

18. Assignments • Regular homeworks will be due 2359 hours each Saturday • But no assignment due on 18 January • Literature assignments are due weekly at 2359 hrs Wednesday • Specific readings already posted might be augmented but not deleted Biochemistry: Introduction

19. Homework, continued Submit OWL assignments through OWLv2 As noted, these count for 6% of grade—not much, but not thing, either Saturday assignments and literature assignments are separate from those Biochemistry: Introduction

20. Lateness? • Regular homework: • 50% penalties for late submissions • 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 Biochemistry: Introduction

21. Schedule, January Biochemistry: Introduction

22. 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: Biochemistry: Introduction

23. 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. Biochemistry: Introduction

24. Organic and biological chemistry • Most molecules in living things (other than H2O, O2, N2, 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: Biochemistry: Introduction

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

26. 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 Biochemistry: Introduction

27. Cell components • Cells are separated fromtheir environments viaa 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 Image courtesythinkquest.com Biochemistry: Introduction

28. Eukaryotes and prokaryotes • Lowest-level distinctionamong organisms ison the basis of whethertheir cells have defined nuclei or not • Cells with nuclei are eukaryotic • Cells without nuclei are prokaryotic • Eubacteria and archaea are prokaryotic • Other organisms are eukaryotic Image courtesyfluwiki.com Biochemistry: Introduction

29. Eukaryotic organelles I • Nucleus: containsgenetic information;site for replication& transcription • Endoplasmic reticulum: site for protein synthesis and protein processing • Ribosome: protein-synthetic machine • Golgi apparatus: site for packaging proteins for secretion and delivery Image courtesyWilliamsclass.com Biochemistry: Introduction

30. 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 Biochemistry: Introduction

31. Eukaryotic organelles III • Chloroplast:site for mostphotosynthetic 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 Image courtesyChloroplast database Biochemistry: Introduction

32. Do prokaryotic cells have organelles? Not as such, but they often have specialized apparatus in them that mirror what organelles do The main difference is that those apparatus don’t typically have lipid bilayers surrounding them and separating them from the cytosol Biochemistry: Introduction

33. 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: Biochemistry: Introduction

34. 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 2 pairs of electrons; or triple bonds, which involve 3 pairs. • Single bonds do not restrict the rotation of other substituents around the bond; double and triple bonds do. Biochemistry: Introduction

35. 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. Biochemistry: Introduction

36. 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. • Non-hydrogen atom to which the hydrogen is covalently bonded is 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 Biochemistry: Introduction

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

38. Van der Waals arithmetic This interaction obeys aLennard-Jones potentialf(r) = -Ar-6 + Br-12 For which the minimum r0 occurs when df/dr = 0,i.e. 0 = 6Ar0-7 – 12Br0-13, or 6Ar0-7 = 12Br0-13Multiplying through by r013/6, we get Ar06 = 2B, soB = ½Ar06, so the potential can be writtenf(r) = -Ar-6(1 – ½(r0/r)-6) Biochemistry: Introduction

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

40. 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. Typically the atom that changes position between the two tautomers is an H atom. Biochemistry: Introduction

41. 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. Biochemistry: Introduction

42. 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. Biochemistry: Introduction

43. 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. • We use the term thermodynamics to describe our understanding of the energetics of equilibrium systems Biochemistry: Introduction

44. 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. I will yell at you if you don’t master this concept. Biochemistry: Introduction

45. Organic Concepts XI Zwitterion: a compound containing both a positive and a negative charge Biochemistry: Introduction

46. Organic nomenclature and depictions • Overarching the above discussion of organic concepts: you should be comfortable with the basics of organic nomenclature and multiple ways of depicting organic molecules. 6-phospho-gluconolactone Biochemistry: Introduction

47. Classes of small molecules 2-oxoglutarate • 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". mevalonate Biochemistry: Introduction

48. 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 hydrophilic moiety. Biochemistry: Introduction

49. Biological small molecules II • Carbohydrates: Polyhydroxylated compounds for which the building blocks are highly soluble. • In addition to the hydroxyls, a carbohydrate will also have one C=O bond either on the end carbon or the carbon adjacent to the end carbon • The typical molecular formula for the monomeric forms of these compounds is (CH2O)n, where 3 < n < 9, but usually n = 5 or 6 (or 3). Biochemistry: Introduction

50. 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- Biochemistry: Introduction