MBB222 Fall 2024 Lecture Notes PDF

MBB222 Fall 2024 DEPARTMENT OF MOLECULAR BIOLOGY AND BIOCHEMISTRY SIMON FRASER UNIVERSITY DR. DUSTIN KING LECTURE 1 (Sept. 4, 2024) Introduction to the course, review of organic chemistry relevant to MBB (part 1)...

MBB222 Fall 2024 DEPARTMENT OF MOLECULAR BIOLOGY AND BIOCHEMISTRY SIMON FRASER UNIVERSITY DR. DUSTIN KING LECTURE 1 (Sept. 4, 2024) Introduction to the course, review of organic chemistry relevant to MBB (part 1) REQUIRED READING: Biochemistry textbook: Chapter 1, pp. 3-17; course policies and course syllabus posted on CANVAS 1 Thank you to the Coast Salish people on whose unceded traditional territories we are gathered. 2 My background. 3  Your Instructor Dr. Dustin King My role at the MBB department Assistant Professor Education BSc Biochemistry (UNBC) PhD Microbiology/Antibiotic Resistance (UBC) Postdoctoral: Chemical Biology (SFU) Area of research Microbial metabolite sensing (CO2 sensing) Hobbies Sports (hockey/skiing) Dogs Watching any season of Survivor 4  Meet your TAs this term Sondos Amran [email protected] Tutorials (begin next week) MBB grad student (Dr. King’s lab) This table is posted to Canvas Office hour: Fri. 9- 10AM, location TBD Tutorial Section Day Time Location TA D101 Mon. 9:30-10:20 AM WMC 2501 SA Harleen Buttar D102 Mon. 10.30-11.20 AM WMC 2501 SA [email protected] D103 Mon. 12.30-1.20 PM WMC 2501 SA FHS alumni D104 Mon. 8:30-9:20 AM AQ 5035 SA Office hour: D105 Tues. 9:30-10:20 AM BLU 10921 JL Wed. 1-2PM, Rm. D106 Wed. 9.30-10.20 AM WMC 3511 JL 6176 D107 Wed. 8.30-9.20 AM WMC 3511 JL D108 Thur. 8:30-9:20 AM AQ 5008 HB Jared Lim D109 Fri. 9.30-10.20 AM WMC 3511 JL [email protected] D110 Tues. 2.30-3.20 PM WMC 3511 HB MBB grad student D111 Mon. 9:30-10:20 AM AQ 5035 HB (Dr. Paetzel’s lab) D112 Wed. 9:30-10:20 AM WMC 2523 HB Office hour: Mon. 3- 5 4PM, location TBD  What we learn in this course Biochemistry: The study of chemical processes occurring in living matter. Every process in life has a biochemical basis. In this course we learn fundamental concepts and process that underly all of life on earth. 6  What we learn in this course Overview of topics Review of organic chemistry Protonation Thermodynamics and catalysis Protein structure Protein function/enzymes DNA structure/replication DNA damage/repair Transcription Translation 7 Course material represents the tip of the iceberg. Provides a taste of what biochemistry is all about and some foundational knowledge 8  Careers in which this material plays a central role: Drug development Medicine/pharmacy/dentistry Science communication Biotechnology Academia Forensics Many others… * We will integrate examples throughout this course. 9 in- LECTURES - introduce new material and relate it to the previously covered material, solve practice problems (Slido) I posted night before I study before ↳ Kagoot ? in TUTORIALS - go over assigned problems - review material, ask questions, and clarify course material - go over midterms - engage and make connections! 10 on CANVAS lecture notes, syllabus, problems for tutorials, practice midterms, course policies, announcements, and your grades at HOME - review lecture notes and solve practice problems - read assigned pages in your textbook - solve tutorial problems (answers posted the week after) - solve practice midterms (answers will be posted) 6  Grading Breakdown Midterm exams 1, and 2 (25% each) 40 minutes in class (see syllabus) Approximately 15 multiple choice + 4-5 short answer questions. Questions examine lecture material. Questions may include diagrams, information prompts, “none of the above” options, etc. Practice midterms (with answers) will be posted on CANVAS 7 tutorials (15% of total grade) as scheduled (see syllabus) 50 minutes. Solve assigned problems with your TA, ask questions, clarify concepts, go over midterms, etc. Your TA will inform you of the specific grading criteria for these 15% in your first tutorial. You are expected to attend all tutorials and actively engage in problem solving and class discussions. ↳ I point tobearction the Cumulative final exam (35% of your final grade) 3 hours Same format as midterms. All lecture material will be covered 12 Required textbook Biochemistry. 2nd Edition. Miesfeld and McEvoy. 2021. W.W. Norton & Company. https://wwnorton.com/books/ 9780393533507 Please do required readings. 13 What’s on our plate this term 14 (see complete syllabus posted on CANVAS)  Course policies Please read and follow the course policies on CANVAS. You are expected to attend all lecture and tutorials: this course will be difficult to complete successfully otherwise. Your instructor expects you to read the assigned pages of your textbook. You are responsible if you miss an exam: Must have a valid medical reason with a doctor’s note ahead of time to miss a scheduled exam. If you anticipate a conflict with any of the scheduled midterms, email your instructor ASAP. You must behave with integrity during examinations. You are expected to interact with your instructors and fellow students in a safe and respectful fashion. Please refer to Student Conduct Policy (http://www.sfu.ca/policies/gazette/student/s10-05.html) 15  IMPORTANT: Course communication 1) Never ask course content questions through email! 2) TAs are your first point of contact for all questions on course content and evaluations (in person). For logistic matters pertaining to tutorials, contact your TA through email. Please do not contact instructor for this. For all course content questions and anything about any course evaluations, please visit them in person during tutorials or in their office hour. Contact instructor by email only for important logistical matters pertaining to overall course or exams, otherwise please visit office hours. Do not ask instructor questions about course evaluations – these should be directed to TA’s Dr. King contact: Email (urgent matters only): [email protected] Office hours: Tuesdays 10-11 AM, SSB-7142 16  Absolutely everything within the requisite course materials – encompassing lecture notes, readings, problem sets, and the like – is open for examination. Please do not ask me “will this be on the exam” 17  What we learn in this course Overview of topics Review of organic chemistry Protonation Thermodynamics and catalysis Protein structure Protein function/enzymes DNA structure/replication DNA damage/repair Transcription Translation 18 19 Intro to organic chemistry relevant to MBB Required readings: Chapter 1, pp. 3-17 Organic molecules are the building blocks of living things – all organic molecules contain carbon (and hydrogen). Organic chemistry is the study of the chemistry of carbon compounds. Carbon-containing compounds were once considered “organ compounds” available only from living organisms. product swaste Synthesis of urea in 1828 by Wohler showed that organic compounds Friedhrich Wöhler (Wikipedia) can be prepared in the laboratory from non-living material. O heat C H 2N NH2 silver ammonium silver isocyanate chloride chloride (used as a fertilizer) ↳ first organic compound Today, organic natural products are routinely synthesized in the laboratory.  20 Examples of organic compounds used as drugs Methotrexate, anticancer drug 5-Fluorouracil, colon cancer drug AZT, HIV drug Tamiflu, influenza drug Tetracycline, antibiotic virus from 4 prevents (anti-bacterial drug) making copies ↳ prevents the bacteria Note that carbons are often represented as “vertices” or lines and their bonded 21 hydrogens are not shown. atom with hydrogen carbon C 8 * How many hydrogen atoms does Benzene to W 7 resonance have bonded ↳ alternating bonds Carbon single/double Methotrexate, anticancer drug benzene Macromolecules studied in MBB 222: DNA, RNA 22 Nucleotides nucleotides RNA (ribonucleic acid) DNA (deoxyribonucleic acid) Macromolecules studied in MBB 222: proteins 23 amino acids peptide protein ↳ perform all the functions in the body ↳ they openaa polypeptide functions Textbook used for CHEM 281/282: refer to it for additional information depth 4 use textbook for more Organic Chemistry, 6th Edition Paula Yurkanis Bruice An introduction to organic compounds: nomenclature, physical properties and representation of structure 20 Carbon: 2nd row of periodic table, near the middle of the row > - electropositive ↳ donateen increasing electropositivity increasing electronegativity ↳ covalent decrons >highifinicons ↳ chare increasing electropositivity increasing electronegativity - 4 pull eclections. (give up e more easily) - (accept e more easily) - Elements on the right side of periodic table are more electronegative and tend to accept electrons. Elements on the left are more electropositive and tend to give up electrons. These elements have opposite charge and tend to form ionic bonds. Elements closer to the center tend to “share” electrons, forming covalent bonds. 21 26 Chemical bonds: ionic vs. covalent bonds ofmoleculaa upper electrons are shared but not equally 4 type unpaired valence electrons Carbon has 4 valence electrons ↳ #6 atomic number H je C +4H = H C H H shared electrons – covalent bond Each of the 4 covalent C-H bonds is made up of an e- pair, with both C and H contributing one e-. 27 Single (covalent) bonds in carbon: valence electrons and sp3 hybridization Carbon has six total electrons distributed over 5 different orbitals. The 1S electrons are non-bonding. However, the 2s and 2p orbitals are available for bonding. 2s 2px 2py 2pz What kind of geometry? trahedral Angles between the C-H bonds? etwa How many bonds are possible? 28 Single (covalent) bonds in carbon: sp3 hybridization; e.g., methane, CH 4 Hydrocarbons Methane C-H bonds are formed by overlap between Carbon sp3 Note: each line between C and and hydrogen 1s orbitals tetrahedral H in methane represents a single bond or a pair of shared s - e- (one from each atom). sp3 4 sp3 orbitals The shared orbitals produce a new sigma ( orbital – the covalent bond formed by the shared electrons is sometimes called a  bond. Tetrahedral geometry: angle between the C-H bonds is 109.5o where are actually Methane, CH4, shown in different representations present 29 Some simple hydrocarbons - alkanes Carban ↳ chains Lewis structure In+ croy Alkanes are hydrocarbons containing only single bonds. They have the general formula: C nH2n+2. Note that both the C-H and C-C bonds are sigma bonds. The C-C bonds are between Sp3 orbitals. of M and # X # of C 30 Carbon-carbon double bonds: sp2 hybridization Oxuntouched 900 trigonal bipyramidal sp2 orbitals have trigonal geometry ethene Double line = double bond or 2 pairs of shaired e-. Ethene (aka ethylene), C2H4, shown in several representations. pence doubleona 31 Carbon-carbon triple bonds: sp hybridization (aka linear sp hybridization) + Sp2 S + p2 - lockedemove Ethyne, C2H2, shown in several representations Note that rotation can occur across a single bond but not a double or a triple bond (what does it mean in terms of flexibility of these molecules in space?) ethane ethene (aka ethylene) ethyne X X -restricted ↳ Sp3 > - Sp2 + can rotate  bond 32 Slido Pentyne On phone 33 Alkyl substituents Removing a hydrogen from an alkane results in an alkyl group or “substituent,” which can bond to other atoms/molecules/groups. substituents (from methane) (from ethane) (from propane) (from butane) M (from pentane) (from alkane) attachment 34 If an alkyl group, R-, is bonded to another atom or functional group: alconol a hydroxyl, OH, the compound becomes an ____________ an amine (amino) group, NH2, the compound becomes an __________ amine halide a halogen (F, Cl, Br or I), the compound becomes an _______________ ether OR, where R is another alkyl group bound to an O, the compound becomes an ________ -OH, –NH2, –I and -OCH3 are examples of “functional groups” – these groups that endow special properties to a compound. Some common names are derived from the alkyl group plus the functional group: alphabet note – the O is part of the functional group 35 Valence shell electrons in C and other elements present in organic compounds ts is lower energy than p. Lewis dot structures – show valence shell electrons H C N O free (bonding) electrons bonding pair (shared electrons – 1 from each atom) lone e- pairs (non-bonding) lone pair Like carbon, nitrogen and oxygen have a 3-dimensional geometry based on their orbitals. Polarity is the asymmetric morectronegativ e ↳ distribution of electrons NH3 - H2O - + +  bonds  bonds 36 Polarity a legative > - positive - + Example What is the difference between non-polar molecules and polar molecules? O2 (dioxygen) – non-polar 37 Polarity is represented using electrostatic potential maps, which show the charge distribution on a molecule non-polar polar - + - + + the O moveronegal te H2O 38 Molecular dipole moment The vector sum of the magnitude and the direction of the individual bond dipole determines the overall dipole moment of a molecule. O H H # ↓ ↳ higher dipole symbol higher dipole monent 39 Functional groups of simple organic compounds have specific properties and reactivity based on their polarity, electronegativity, etc. They are more reactive than their alkyl substituents. Alcohols – the functional group is a hydroxyl, -OH Thiol – the functional group is a sulfhydryl, -SH (also called a thiol) ↳ larger size Acids – the functional group is a carboxyl, COOH, comprised of a carbonyl group (a carbon with a double-bond to an oxygen) bonded to a hydroxyl group via the carbon proton donates carbonyl 4 Acid- COOH = carboxyl COO- = carboxylate ion (HCOOH) (CH3COOH, vinegar) HCOOH HCOO- + H+ CH3COOH CH3COO- + H+ organic acids can give up a hydrogen, becoming negatively charged carboxylate ions 40 More functional groups: amines, amides Amines – the functional group is a nitrogen – is basic (can be protonated) ↳ initially neutral 4) function as a base+ accepts a proton CH3NH2 + H+ CH3NH3+ amines can acquire a hydrogen, becoming positively charged methylamine Amides – the hydroxyl group of a carboxylic acid is replaced by an amine group ↳ not ionizable ↳ highly polar acetamide glycylglycine, or diglycine 41 More functional groups: ethers, ketones, esters, aldehydes Aldehyde – very reactive Ketones – acetone (nail polish remover) acetaldehyde Ether – Ester – very stable R2 R1 R2 R1 dimethyl ether methyl acetate 42 Can you recognize the functional groups on diglycine? amine L acid ~ carboxlyic amide Reminder: carbons are often represented simply as “vertices” or lines and their bonded hydrogens are not shown. 2H Sp3 , SP2 43 Functional groups table (carbonyl)