Chemistry 271 Introductory Biochemistry I Fall 2024 PDF

Chemistry 271 – Introductory Biochemistry I Fall 2024 Joanne Krupa Office hours: Tues. & Thurs. 10:10 am -11:10 am L-SP 201.04 Email:...

Chemistry 271 – Introductory Biochemistry I Fall 2024 Joanne Krupa Office hours: Tues. & Thurs. 10:10 am -11:10 am L-SP 201.04 Email: [email protected] All figures not specifically referenced either come from: J. M. Berg et al., Biochemistry 7th edition. W. H. Freeman and Company, 2010. J. M. Berg et al., Biochemistry 8th edition. W. H. Freeman and Company, 2018. Figures from: J. M. Berg et al., Biochemistry 10th edition, W.H. Freeman MacMillan Learning, 2023 are specified Many figures come from A.L. Lehninger, Principles of Biochemistry, 6th edition. W.H. Freeman, 2013, Permission granted to use all these figures Due to copyright laws, you CANNOT POST NOR DISTRIBUTE these lecture notes or any course material. They can only be used for personal educational purposes pertaining to this course. 1  The required textbook: BIOCHEMISTRY, 10th Edition Jeremy Berg; Gregory Gatto Jr.; Justin K. Hines; John L. Tymoczko; Lubert Stryer ©2023, W.H. Freeman MacMillan Learning But 7th, 8th, or 9th editions are acceptable! Note: ebook available on Macmillan site Lecture slides posted on Moodle at least 3-4 days in advance of lecture 2  The required online homework tool : Achieve Essentials (©macmillan learning) NOT Achieve One homework assignment assigned per week, open in general for about 2 weeks (depending if we are on schedule lecture wise) Postings on Mondays and due 14 days later (at 11:59 pm), except the 1st one Why use? Increases exam scores by about 8% Registration is ~ $50 …for instructions see Syllabus For technical problems: see syllabus Biochemistry I - Fall 2024 - Krupa https://achieve.macmillanlea rning.com/courses/dbjg5m Slide posted with permission from Macmillan Learning July 3, 2024 3  Grade breakdown Laboratory/Tutorial: 25% On-line homeworek Achieve Essentials 5% Midterm exams (IN PERSON): 35% Oct. 8, 2024 and Nov. 14, 2024 (15% + 20% ; your best exam of the two will be worth 20%) Cumulative Final exam (IN PERSON): 35% Total: 100% You must separately pass the lab component of the course as well as the lecture/theory components. You must pass the lecture/theory (including Achieve Essentials) component with a weighted average of 50%. You must pass the lab component (includes tutorials) with a weighted average of 60%. 4  Chem 101 You are only exempt from repeating the seminar and the quiz if you have done both in Fall 2019 or more recently Date (Fall Time Mode Registration link 2024) Sept. 17 21:00- Zoom https://concordia- (Tuesday) 22:00 ca.zoom.us/meeting/register/tZIudu2hpz0pHdEgCP92- BqKLe72B8dN00VJ Sept. 19 21:00- Zoom https://concordia- (Thursday) 22:00 ca.zoom.us/meeting/register/tZcudO2qpzkpEtK3A1OJpP6ueDBhn7PD eQqa Sept. 23 21:00- Zoom https://concordia- (Monday) 22:00 ca.zoom.us/meeting/register/tZEsfuuqqjIuHNJREfSfHWhoDfmL50Q7 CU7Q You are exempt if you can locate your ID in the pdf file located on the Departmental web site (http://www.concordia.ca/content/dam/artsci/chemistry/docs/Compliance-list.pdf) and if there is no entry in the “quiz” column for you. Make sure that the compliance list is the F2019-S2024 version. If it is not, clear your browsing data. 5  What is biochemistry? BIOLOGY CHEMISTRY The study of the The study of the structure, organization structure, organization and interactions of cells, and interactions of atoms tissues and organisms and molecules BIOCHEMISTRY The study of the structure, organization and functioning of living matter in molecular terms  The chemistry of life 6  Course overview (Part I): Structure of proteins & enzymology Isolation of proteins Protein purification Quaternary Tertiary structure structure Hemoglobin (structure & function) Basic Secondary structure enzymology concepts Enzyme kinetics Enzyme inhibition Primary structure Amino acids Acids & bases Enzyme Mechanisms Lehninger, Principles of Biochemistry 6th edition. 7  Course overview (Part II): Coordination of enzymes to convert glucose to ATP Citric acid cycle Metabolism: Glycolysis Gluconeogenesis Glycogen metabolism Oxidative phosphorylation (Electron-transport chain) Carbohydrates (structure & function) Oxidative phosphorylation (ATP synthesis) Enzyme regulatory strategies and how enzymes are a part of metabolic pathways Lehninger, Principles of Biochemistry 6th edition. 8  NOTE: This section (slide 9-16) was taught in lower courses Review this section on your own as needed Only slide 10 – summary will be explained in class Covalent bonds and noncovalent interactions Important for stability of biological molecules All figures not specifically referenced either come from: J. M. Berg et al., Biochemistry 7th edition. W. H. Freeman and Company, 2010. J. M. Berg et al., Biochemistry 8th edition. W. H. Freeman and Company, 2018. Figures from: J. M. Berg et al., Biochemistry 10th edition, W.H. Freeman MacMillan Learning, 2023 are specified Many figures come from A.L. Lehninger, Principles of Biochemistry, 6th edition. W.H. Freeman, 2013, Permission granted to use all these figures Due to copyright laws, you CANNOT POST NOR DISTRIBUTE these lecture notes or any course material. They can only be used for personal educational purposes pertaining to this course. 9  Covalent bonds & non-covalent chemical interactions Polypeptide backbone Ionic Bond: electrostatic Hydrogen bond Covalent bond: Disulfide Linkage Hydrophobic Interactions Chemical interactions are required for stability and folding of proteins Covalent bonds are the strongest chemical interaction (e.g. O-H bond 470 kJ/mol)! Image accessed with minor modifications on July 3 , 2024, Credit (CC BY-NC-ND 4.0): Farzan Soleymani et al., Computational and Structural Biotechnology Journal, 20, (2022), 5316-5341: https://doi.org/10.1016/j.csbj.2022.08.070 10  Hydrogen bonding in water The dipole moment of water leads to a dual character; – an H donor – an H acceptor Up to four H-bonds per water molecule Hydrogen bonding in water is cooperative: when one forms, it encourages another to form Lehninger, Principles of Biochemistry 6th edition. 11  Hydrogen bonds do not have to involve water – + – 2.4 Å to 3.5 Å When the two electronegative atoms and one H are in a H-bond: straight line, electrostatic A + hydrogen atom shared between two interactions are maximized highly electronegative atoms (usually N, O, and stronger H-bonds or S in biological systems); a hydrogen generated. bond acceptor (often lone pair) & a  H-bonds tend to be hydrogen bond donor straight (see slide 11) Is weaker than covalent bonds, thus longer (2.4 Å -3.5 Å) Bond energy: 4-20 kJ/mol Lehninger, Principles of Biochemistry 6th edition. 12  Electrostatic (ionic) interactions Exist between two charged groups forming a salt bridge Attractive Repulsive Can also occur between a charge species and a permanent dipole Vary in strength depending on the nature of the species Coulombs law 𝑘𝑞1 𝑞2 𝐹= 𝐷𝑟 2 F: force q1 and q2: charges D: Dielectric constant (D= 80 H2O, D= 1 vacuum) r: distance between charges k: proportionality constant Bond energy 5.8 kJ/mol for singly charged ions separated by 3Å in H2O Lehninger, Principles of Biochemistry 6th edition. 13  van der Waals interactions Bond energy: 2 – 4 kJ/mol Weak interactions between all atoms, regardless of polarity i. Attractive (dispersion) component ii. Repulsive (steric) component At longer distances, attraction dominates. Energy between atoms is most favorable at van der Waals contact distance. If two atoms are closer than this distance, electron-electron repulsion occurs. 14  London dispersion forces Within a bond or atom, electrons are constantly moving, so there are situations for a very short time where parts of the bond or atom are more negative than other parts. Electron clouds become polarized, inducing dipoles! Transient temporary electronic asymmetries in one molecule induce complementary interaction in the partner molecule Stronger in polarizable molecules Important only at a short range. +- +-+ +- + +- +- ++ - +- -+-+ +- ++- +- -+ - +- + -+ +- + - -+- + attraction 15  Hydrophobic interactions Non polar molecules aggregate in water (polar solvent) Why? Favorable for them to do so because they release water molecules that formed a cage around them, thus maximizing entropy and making the process thermodynamically favorable Recall: DG = DH -TDS 16  Amino acids & peptides All figures not specifically referenced either come from: J. M. Berg et al., Biochemistry 7th edition. W. H. Freeman and Company, 2010. J. M. Berg et al., Biochemistry 8th edition. W. H. Freeman and Company, 2018. Figures from: J. M. Berg et al., Biochemistry 10th edition, W.H. Freeman MacMillan Learning, 2023 are specified Many figures come from A.L. Lehninger, Principles of Biochemistry, 6th edition. W.H. Freeman, 2013, Permission granted to use all these figures Due to copyright laws, you CANNOT POST NOR DISTRIBUTE these lecture notes or any course material. They can only be used for personal educational purposes pertaining to this course. 17  Amino acids: Building blocks of proteins Proteins are linear heteropolymers of -amino acids. Amino acids have properties that are well-suited to perform a variety of biological functions – Ability to polymerize – Diverse chemical functionality (acid, base, neutral) ― Diverse physical properties (hydrophilic, hydrophobic) They possess the diversity that allows proteins to function! amino acids come together to allow the protein to have the function it needs Lehninger, Principles of Biochemistry 6th edition. 18  Components of -amino acids The -carbon is tetrahedral and always has four substituents; – an acidic carboxyl group (COOH) – a basic amino group (NH2) – an hydrogen connected to the -carbon – a fourth substituent (R) that is unique to each amino acid In glycine, the fourth substituent is a hydrogen C H amino -carbon acid -amino acid 19  Amino acids share many features, differing only at the R substituent General structure of an amino acid. If R is not a hydrogen, then the amino acid is chiral. Lehninger, Principles of Biochemistry 6th edition. 20  All amino acids are chiral (except glycine) enantiomers L-isomer: D-isomer: L-alanine D-alanine mirror plane All amino acids are chiral (lack a plane of symmetry & do not have superimposable mirror images) except for glycine since the R group is a hydrogen.  L-alanine and D-alanine are a pair of enantiomers  Proteins only contain L-amino acids Lehninger, Principles of Biochemistry 6th edition. 21  L vs D amino acids: Fisher projections L-alanine D-alanine Fisher projection Place the most oxidized carbon on top If NH3+ group is mirror plane on the left, it is an L- amino acid, based on its resemblance to L- glyceraldehyde L-glyceraldehyde Lehninger, Principles of Biochemistry 6th edition. 22  L-amino acids are of the (S) configuration (except for cysteine) 3 1 4 4 2 3 2 (S)-Alanine (R)-Cysteine Images accessed on July 3, 2024: Credit: Benjah-bmm27, Public domain via Wikipedia commons: https://commons.wikimedia.org/wiki/File:L-alanine-3D-balls.png 23 Benjah-bmm27, Public domain via Wikipedia commons: https://commons.wikimedia.org/wiki/File:L-cysteine-3D-balls2.png  Amino acids: Classification The 20 most common amino acids are placed in four different groups depending on the chemistry of the R substituent at pH 7.0: 1. Hydrophobic amino acids with non polar R groups (9) 2. Polar amino acids (6) 3. Amino acids with positively charged side chains (3) 4. Amino acids with negatively charged side chains (2) Structures shown in next slides show ionization predominating at pH 7.0 The 20 amino acids found in proteins contain unique side chains that vary in: i. Size ii. Shape iii. Charge iv. Hydrogen-bonding capability v. Hydrophobic/hydrophilic character vi. Chemical reactivity  These different features allow proteins to function. 24  Hydrophobic amino acids (achiral) * * additional chiral centre Hydrophobic amino acids tend to cluster together and avoid water. Glycine is the least and phenylalanine the most hydrophobic (in this set). Glycine is achiral and isoleucine contains two chiral centres Data obtained on Aug. 5, 2024: Credit: Widyarani, Sari, Y.W., Ratnaningsih, E. et al. Appl Microbiol Biotechnol 100, 7909–7920 (2016): https://doi.org/10.1007/s00253-016-7441-8 25  Hydrophobic amino acids * Unlike other amino acids, proline contains a secondary amine.  This restricts the conformation of proline, a feature exploited by proteins. 26 Polar amino acids * * = additional chiral centre These amino acids have side chains displaying electronegative atoms that can form hydrogen bonds. These polar OH and CONH2 groups make these amino acids hydrophilic (strong affinity for water). Cysteine is an outlier in this group. It can also form disulfide bonds and it can also be partly deprotonated at physiological pH. 27 Cysteine can form disulfide bonds Disulfide bond 28  On your own Amino acids with aromatic side chains Phenylalanine is purely hydrophobic. Tryptophan and tyrosine are less hydrophobic than phenylalanine due to the presence of OH and NH on the side chain. Tyrosine is somewhat polar. These three amino acids absorbs UV light at  280 nm. Lehninger, Principles of Biochemistry 6th edition. 29  On your own Amino acids with aromatic side chains Absorbance of UV light at 280 nm is due to the presence of the aromatic ring. Tryptophan absorbs the most light at 280 nm. The absorbance at 280 nm allows for the quantification of protein concentration. Lehninger, Principles of Biochemistry 6th edition. 30  Positively charged amino acids (or at least some amount at neutral pH) e  g b α Lysine and arginine are charged amino acids with R groups displaying a positive charge at neutral pH. They are highly hydrophilic. Histidine has an R group that is partly positively charged at pH 7.0 31  Histidine Histidine contains an imidazole group in its side chain.  It can bind or release protons at physiological pH depending on its local environment (note the delocalization of electrons)  pKa 6.0 (get to soon) 32  Arginine Arginine contains an guanidinium moiety in its side chain Note the delocalization of electrons. 33  Negatively charged amino acids Aspartate and glutamate are charged amino acids with R groups displaying a negative charge at neutral pH. They are hydrophilic (asp being the most). These amino acids are also named aspartic acid and glutamic acid. However the names aspartate and glutamate are often used due to the negatively charged carboxylate group at physiological pH Note the delocalization of electrons. 34 Abbreviations for the 20 Amino Acids First letter of name except: Arg, Asn, Asp, Gln, Glu, Lys, Phe, Trp & Tyr First 3 letters of name except: Asn, Gln, Ile & Trp 35  On your own Tutorial 1 quiz You must know for tutorial quiz 1 : 1. The names 2. The three-letter code 3. The one-letter code For all the 4. The characteristics 20 common amino acids 5. How to draw the chemical structures 6. Their pKa’s…next class 7. Ionizable groups in amino acids … next class 8. How do solve pH / buffer problems …. next class Note you have a quiz in your first tutorial! 36  On your own Why aren’t other amino acids found in proteins? Too reactive! For example... Can form a stable 5- membered ring. Note that if X is an adjacent amino acid, cleavage would occur. Serine does not cyclize because the 4- membered ring is sterically unfavorable That’s why serine is found in proteins but not homoserine 38  In class problem What group of amino acid does the amino acid shown belong to? A. hydrophobic B. polar C. negatively charged D. positively charged 39  In class problem Which one(s) of the following amino acids has two chiral centres? A. Arginine B. Aspartate C. Glutamate D. Isoleucine E. Threonine 40  In class problem Which one of the following amino acids has an uncharged side chain under physiological conditions A. Arginine B. Aspartate C. Glutamate D. Lysine E. Threonine 41