Download bioCHEMISTRY 480 Molecular Biochemistry-‐

bioCHEMISTRY 480 Molecular Biochemistry-­‐-­‐The Macromolecules Autumn 2014 Dr. Jeff Corkill SCI 232 Telephone 359-­‐6518 Email: [email protected] Textbook: Fundamentals of Biochemistry by Voet, Voet and Pratt 4thEd OfficeHours: Daily 9:15 to 10:30am MW 2-­‐4pm or by appointment Reference Books: Biochemistry, Voet, Voet & Pratt, 3/E On reserve In JFK Library In addition in the QP500-­‐600 Section of JFK Library [lower right hand back corner] there is a wide variety of biochemistry books. Some of these are general undergraduate textbooks whereas many others deal with special topics (Adams et al., Kornberg, Baldwin, Orten & Newhaus, etc.). Make an effort to check out this area! Clinical chemistry books are under the RA and RB heading. RasMol and Astex: molecular modeling freeware programs will be used to prepare an individual bioinformatics web-­‐based document on a specific enzyme protein. Raw data can be manipulated/rendered into structural representations of the proteins. Web-­‐
based search for protein and DNA sequence data will be obtained and homologous sequences examined. Homepage: http://sites.ewu.edu/jcorkill/ http://chemistry.ewu.edu/jcorkill/biochem/48014.htm The subsections of this page are: (1) Introduction & curriculum, biochemical aims , research aims, overall course learning targets, Voet’s web site (2) Lectures Notes, (3) Keys to Spring 2014 tests, (4) Keys to Autumn 2014 tests, quizzes, homework, (5) Learning targets,(6) 480 Ramachandran’s Blog (7) Related biochemistry web sites, (8) Biochemical informatics (9) Lecture Notes on Chromatography . CourseApproach: This course will study the chemical principles of structure and interactions of chemical species that pertain to biochemical systems and then attempt to explain the systems themselves. The course is organised so as to encourage a natural transition from organic chemistry to biochemistry. The major theme is the ‘structure-­‐> (re) activity in vivo -­‐> biological function’ relationship. The textbook (‘Voet’) has been chosen for EWU’s future biochemistry courses (CHEM480, 481& 482) collaboratively by Drs. Jeff Corkill & Nick Burgess to reinforce this theme. This assumes that reactions which occur in nature are only "variations on a theme" of those which are found (and you have studied!) in organic chemistry. The factors that control and/or influence "organic" reactions in vitro are analogous to those found in nature-­‐in vivo. It is assumed (no !-­‐demanded!) that students will have a working knowledge of organic chemistry especially from mechanistic and energetics aspects (that’s why a 2.0 grade in CHEM352 is a pre-­‐
requisite!!). Pre-­‐requisites: The following are topics of which you are assumed to be familiar with for this 400-­‐level bioChemistrycourse from your previous studies: (a) Factors which influence reactivity-­‐-­‐electronic factors (inductive and resonance effects), steric hindrance, solvent, pH, ionic strength, temperature, catalysts, etc. (b) Factors which influence both inter-­‐ and intra-­‐molecular interactions (ionic attraction and repulsion, ion-­‐dipole, hydrogen bonding, dipolar attraction, London dispersion forces [ called ‘hydrophobic interactions’ when water is the solvent as in life on Earth] (c) Mechanisms in organic reactions: (i) Nucleophilic substitution at >C=Oand >P=O (reactions of amides, esters, phosphate esters, carboxylic acids and carboxylate anions) (ii) Nucleophilic addition at >C=O (reactions of aldehydes & ketones) and to a much lesser degree: (iii) Elimination reactions at saturated carbon (E1, E2) (iv) Electrophilic addition at >C=C< IT IS ESPECIALLY IMPORTANT TO UNDERSTAND THE CHEMISTRY OF (1) CARBOXYLIC ACIDS, ESTERS AND AMIDES & (2) SACCHARIDES Memorise: (i)
ACID + ALCOHOL= ESTER + WATER (and reverse by hydrolysis!!!) (ii)
ACID + AMINE = AMIDE + WATER (and reverse by hydrolysis!!!) (iii)
ALDEHYDE+ALCOHOL=HEMIACETAL then +another ALCOHOL -­‐>ACETAL (and reverse by hydrolysis!!!) (iv)
ALDEHYDE+ primary AMINE = IMINE (and reverse by hydrolysis!!!) (d) Kinetics-­‐ order of reaction, rate constants, reaction profiles, transition states, intermediates, ΔG‡, ΔH‡, ΔS‡, and the concept of transition states, etc. (e) Equilibria-­‐equilibrium constants, position of equilibria, endo-­‐ and exogonic reactions, ΔGo, ΔHo, ENTROPY ΔSo etc. A list of "Learning targets " for each test will be posted on the web site several days before each test & will be discussed the day before each test. You should be aware that, in studying biochemistry in a manner described above, answers to questions on tests and homework will consequently have to be approached from a molecular biochemical angle and not a biological one. Biological answers will get little credit and typically a red B! Further, it is important to answer the question asked not another question of your choice (avoid the remark ‘true but not the answer to this question on your paper) Homework: There will be handed out as problem sets. They are intended to be practice for the next test. They will not be all graded but keys will be posted on the website. In addition, there will be online homework from the Open learning Initiative (‘OLI”) sponsored by the Carnegie-­‐Mellon University. These can be access via www.oli.org. The course key is 48014Sp and the course password is VVP4 You need to self enroll at the URL above. All of these will count for 15% of overall grade. Quizzes: These will cover the assigned material and be both individual and group in form. Some of the assigned reading will be from (1) the textbook (2) research papers and (3 )the Science section of the . A discussion of the questions will follow. This will mean more learning on your own and less lecturing in order to achieve mastery of the topic(s). These will count for 15% of overall grade. No make ups! Grades: There will be four "hourly" tests on (tentatively): th #1 Monday 13 October, #2 Wednesday 29th October, #3 Friday 14th November, & #4 Monday 1st December. The 4 test scores will count for 40% of the grade (there are NO make-­‐ups). 30% will be derived from quizzes and homework. An individual bioinformatics project on enzyme structure will count 5%. A comprehensive final (12/11/14 @ 12noon) will count 25% There are NO points for attendance (but it's recommended!) Your grade is determined from your average score (%) and Dr. Eva Excel, i.e. Course Grade = (2.25x10-­‐1[%]) -­‐ (1.1x10-­‐3[%]2) -­‐7.10 i.e. an A-­‐ (3.7) is >77.5%, a B-­‐ (2.7) is >63%, a C-­‐ (1.7) >53%, a D-­‐ (>0.7) >45% (&<45% fails.) A graph of % versus grade is on the 480 web under Lecture Notes Ethics and Manners: Be aware of the consequences of your action on other students in the course. Turn off the noisemaker of cell ‘phones and OR ELSE! AND THAT MEANS NO TEXTING OR CELL PHONE USE IN THE LECTURE ROOM!. Violators will be first warned after which grades will be lowered. If you know a call may arrive during class, use the vibrate mode and sit near the door. CURRICULUM (referenced to Voet, Voet& Pratt 4th Ed.) 1. Overview [Chapters 1 & 2]& Review of Biochemistry (on website) (a) naturally occurring compounds of living matte (b) organization in living organisms (c) structure-­‐-­‐activity-­‐-­‐functions relationships (d) inter and intra-­‐molecular bonding (e) pH, ionized species and buffers (f) bio-­‐energetics: thermodynamics of living organisms 2 . The Chemistry, Biological Structure and Functions of Amino Acids & Proteins [Chapters 4, 5, 6 & 7] (a) amino acids (b) proteins: structure/activity/biological function (c )primary, secondary, tertiary and quaternary structure of polypeptides and proteins (d) conformations, protein folding and thermodynamics (e) oxygen-­‐transporting proteins, allosterism&cooperability, (f) experimental biochemistry: chromatography and electrophoresis 3. Glycochemistry: The Saccharides: Structure/activity/biological function relationships [Chapter 8] (a) mono-­‐saccharides (b) di-­‐saccharides (c) oligo-­‐-­‐saccharides (d) poly-­‐-­‐saccharides (e) glycoproteins and proteoglycans 4. Lipids, Cholesterol metabolism, Biological Membranes & Membrane Transport [parts] [Chapters 9, 10 & parts of 20] (a) structure& function of lipids (b) transport and metabolism of cholesterol and triglycerides (c) structure and function of membranes 5. Enzymology [Chapters 11 & 12] (a) Bio-­‐molecular mechanisms, (b) Michaelis-­‐Menten kinetics, and (c ) regulation in vivo 6. Nucleotides, DNA & RNA and Recombinant DNA [Chapter 3] (a) nucleotides& nucleic acid structure (DNA and RNA) (b) nucleotidesroles of nucleic acids (DNA and RNA) (c) the 'Central Dogma' , (d) Structural analysis of nucleic acids (e) genomics and bioinformatics