Biochemistry I (CHM 4621) Course Overview - PDF

Biochemistry I (CHM 4621) Dan Kraut, Ph.D. 8/26/24 1 Biochemistry I (CHM 4621) Dan Kraut, Ph.D. 8/26/24 1 Introductions 2  Introductions About me 2  Introductions About me Undergrad at Swarthmore, biochemistr...

Biochemistry I (CHM 4621) Dan Kraut, Ph.D. 8/26/24 1 Biochemistry I (CHM 4621) Dan Kraut, Ph.D. 8/26/24 1 Introductions 2  Introductions About me 2  Introductions About me Undergrad at Swarthmore, biochemistry 2  Introductions About me Undergrad at Swarthmore, biochemistry Ph.D. in biochemistry from Stanford studying enzyme mechanism 2  Introductions About me Undergrad at Swarthmore, biochemistry Ph.D. in biochemistry from Stanford studying enzyme mechanism Postdoc at Northwestern, studying the proteasome, teaching biochemistry 2  Introductions About me Undergrad at Swarthmore, biochemistry Ph.D. in biochemistry from Stanford studying enzyme mechanism Postdoc at Northwestern, studying the proteasome, teaching biochemistry 13th year here at Villanova teaching this class 2  Introductions About me Undergrad at Swarthmore, biochemistry Ph.D. in biochemistry from Stanford studying enzyme mechanism Postdoc at Northwestern, studying the proteasome, teaching biochemistry 13th year here at Villanova teaching this class Teaching is always a work in progress, feedback is valued as we go 2  Introductions About me Undergrad at Swarthmore, biochemistry Ph.D. in biochemistry from Stanford studying enzyme mechanism Postdoc at Northwestern, studying the proteasome, teaching biochemistry 13th year here at Villanova teaching this class Teaching is always a work in progress, feedback is valued as we go 2 kids (11th/6th grade), 2 guinea pigs 2 Introductions  Introductions Attendance Introductions 4  Introductions Attendance 4  Introductions Attendance More about you: Notecard 4  Introductions Attendance More about you: Notecard Name, major, year 4  Introductions Attendance More about you: Notecard Name, major, year One interesting thing about you 4  Introductions Attendance More about you: Notecard Name, major, year One interesting thing about you Why are you a biochem major/minor/concentration OR, if you aren’t, why are you taking biochemistry? 4  Introductions Attendance More about you: Notecard Name, major, year One interesting thing about you Why are you a biochem major/minor/concentration OR, if you aren’t, why are you taking biochemistry? Getting to know you better - coffee chats? 4  Expectations Come to lecture, ask questions, participate in any discussions. Do the reading - I’ll try and indicate what I’m focusing on if not the whole chapter, i’ll post lecture notes beforehand so you see what I’ll talk about Be prepared to actively engage with lots of challenging, interesting material, both in class and on your own/in groups. Give me feedback on what you are learning, what you aren’t learning 5  Expectations This is NOT gen chem, gen bio, orgo, etc - this is the big leagues… Expectations are higher for understanding and applying versus memorizing You will be challenged, struggle at times I’m here to support you, give you the help you need to succeed - my door is (almost) always open (can often zoom at a moment’s notice) Optional problem sessions - Fridays at 12:50? 6 Evaluation/Grading 8  Evaluation/Grading Quizzes (60%) Every chapter or so, 20 minutes (bold in syllabus) Focus on material since last quiz (bring calculator) Generally at the end of a topic/chapter Lowest scores dropped (8 quizzes, 2 dropped) Quizzes/tests will be challenging - an 80% or less on a quiz may very well translate into an A Quizzes will help you learn! In-class/at-home group assignments will count as quiz grades as well. 8  Evaluation/Grading Quizzes (60%) Every chapter or so, 20 minutes (bold in syllabus) Focus on material since last quiz (bring calculator) Generally at the end of a topic/chapter Lowest scores dropped (8 quizzes, 2 dropped) Quizzes/tests will be challenging - an 80% or less on a quiz may very well translate into an A Quizzes will help you learn! In-class/at-home group assignments will count as quiz grades as well. Homework - Achieve - (12.5%) Goes along with each quiz, due by 4:30 pm 2-3 days before quiz. 8  Evaluation/Grading Quizzes (60%) Every chapter or so, 20 minutes (bold in syllabus) Focus on material since last quiz (bring calculator) Generally at the end of a topic/chapter Lowest scores dropped (8 quizzes, 2 dropped) Quizzes/tests will be challenging - an 80% or less on a quiz may very well translate into an A Quizzes will help you learn! In-class/at-home group assignments will count as quiz grades as well. Homework - Achieve - (12.5%) Goes along with each quiz, due by 4:30 pm 2-3 days before quiz. Clickers - graded based on participation rate (7.5%) 8  Evaluation/Grading Quizzes (60%) Every chapter or so, 20 minutes (bold in syllabus) Focus on material since last quiz (bring calculator) Generally at the end of a topic/chapter Lowest scores dropped (8 quizzes, 2 dropped) Quizzes/tests will be challenging - an 80% or less on a quiz may very well translate into an A Quizzes will help you learn! In-class/at-home group assignments will count as quiz grades as well. Homework - Achieve - (12.5%) Goes along with each quiz, due by 4:30 pm 2-3 days before quiz. Clickers - graded based on participation rate (7.5%) Final (20%) - cumulative - like a bunch of quizzes 8 Historical grade distributions (Without a curve) 9 Machines inside of us Drew Berry, 2003 10 wehi.edu.au Machines inside of us Drew Berry, 2003 10 wehi.edu.au Machines inside of us How can we study something so complex? Drew Berry, 2003 10 wehi.edu.au Brainstorm 11  Brainstorm What types of smaller “molecular” steps are required for complex cellular processes (like translation) to occur? Looking for common/general themes 11 What is Biochemistry? 13 What is Biochemistry? The idea that biology can be understood by taking a reductionist approach: Taking each piece of a system, guring out how it works, starting from chemical and physical approaches Putting pieces back together to understand how the larger system works 13 fi What is Biochemistry? The idea that biology can be understood by taking a reductionist approach: Taking each piece of a system, guring out how it works, starting from chemical and physical approaches Putting pieces back together to understand how the larger system works Put another way: Nothing in the cell is magical, and everything in biology can be reduced to a chemical reaction 13 fi Course Learning Objectives Become familiar with the primary macromolecules in the cell (proteins, nucleic acids, lipids, carbohydrates), their components and their chemistry. Understand the connection between macromolecular structure (including dynamics and conformational change) and function. Proteins work by binding to things Explain the chemistry of biological reactions. Biological reactions obey the laws of thermodynamics. All reactions are driven toward a particular equilibrium state. Reaction catalysis affects rates, not fundamental driving force. We can use reaction rates to understand the energetics of the transition states. Become familiar with the basic tools scientists use to study biochemistry and molecular biology and understand their theoretical bases. 14 Course Overview 15  Course Overview Introduction 15  Course Overview Introduction Origin of life, evolution of cellular architecture 15  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game 15  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules Nucleic acids & information 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules Nucleic acids & information Amino acids & proteins - structure and function 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules Nucleic acids & information Amino acids & proteins - structure and function Protein structure and folding 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules Nucleic acids & information Amino acids & proteins - structure and function Protein structure and folding Protein function - binding, transport & catalysis 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules Nucleic acids & information Amino acids & proteins - structure and function Protein structure and folding Protein function - binding, transport & catalysis Carbohydrates 15 fi  Course Overview Introduction Origin of life, evolution of cellular architecture Thermodynamics - the rules of the game Water - the playing eld Biomolecules Nucleic acids & information Amino acids & proteins - structure and function Protein structure and folding Protein function - binding, transport & catalysis Carbohydrates Lipids & membranes - transport 15 fi  In e beginning... Today’s Learning Objectives Be able to summarize the early stages of chemical evolution Explain the role of complementarity and self-replication Explain the selective advantage conferred by compartmentalization Use the endosymbiotic hypothesis to explain evolution of cell types Differentiate between the evolutionary domains of life Understand the role evolution plays today Explain why past changes constrain future evolution 16 th Origin of life 17  biomolecules Origin of life 17  biomolecules Origin of life Early atmosphere: small, simple compounds, reducing atmosphere (no oxygen): H2O, N2, CO2, CH4, NH3, H2S 17  biomolecules Origin of life Early atmosphere: small, simple compounds, reducing atmosphere (no oxygen): H2O, N2, CO2, CH4, NH3, H2S O H Simple N R' R OH biomolecules H 17  biomolecules Origin of life Early atmosphere: small, simple compounds, reducing atmosphere (no oxygen): H2O, N2, CO2, CH4, NH3, H2S Lightning? O H Simple N R' R OH biomolecules H 17  Janet Iwasa exploringorigins.org 18 19  Hypothesis: Early reducing environment + lightning 19  Hypothesis: Early reducing environment + lightning 1953: Miller & Urey zapped gas mix for ~1 week Got organics, including amino acids, out Relies on absence of oxygen 19  Hypothesis: Early reducing environment + lightning 1953: Miller & Urey zapped gas mix for ~1 week Got organics, including amino acids, out Relies on absence of oxygen Depending on nature of the gas mix, other components, either works or doesn’t Still an active area of research 19  Alternatives: Hydrothermal gas vents + seawater Hypothesis: Early reducing environment + lightning 1953: Miller & Urey zapped gas mix for ~1 week Got organics, including amino acids, out Relies on absence of oxygen Depending on nature of the gas mix, other components, either works or doesn’t Still an active area of research 20  Alternatives: Hydrothermal gas vents + seawater Extraterrestrial origin + meteor strike Hypothesis: Early reducing environment + lightning 1953: Miller & Urey zapped gas mix for ~1 week Got organics, including amino acids, out Relies on absence of oxygen Depending on nature of the gas mix, other components, either works or doesn’t Still an active area of research 21 End up with organic matter 22 End up with organic matter Mostly composed of C, N, O, H A bit of P, S 22 End up with organic matter Mostly composed of C, N, O, H A bit of P, S Contain a set of common functional groups (Table 1-2 in your book) Do whatever the molecule needs to do... Different reactivities (e.g. nucleophile/electrophile) 22  Origin of Life O H N R' R OH H 24  Origin of Life O O + H 2N H 2N OH OH O H 2N OH N H O 25  Origin of Life O O + H 2N H 2N OH OH O O H 2N OH + H 2N N OH H O O O H H 2N N N OH H O 25  Biopolymers formed by condensation 26 Functional groups allow interaction 27  Interaction allows self- complemetarity, internal structure 28  Interaction allows self- complemetarity, internal structure What happens if it unfolds in the presence of more monomers? 28  Interaction allows self- complemetarity, internal structure What happens if it unfolds in the presence of more monomers? 28  Interaction allows self- complemetarity, internal structure What happens if it unfolds in the presence of more monomers? Catalyzed condensation reactions? (high local concentration) 28  Interaction allows self- complemetarity, internal structure What happens if it unfolds in the presence of more monomers? Catalyzed condensation reactions? (high local concentration) Refolding 28  Interaction allows self- complemetarity, internal structure & self-replication! What happens if it unfolds in the presence of more monomers? Catalyzed condensation reactions? (high local concentration) Refolding 28  Interaction allows self- complemetarity, internal structure & self-replication! What happens if it unfolds in the presence of more monomers? Catalyzed condensation reactions? (high local concentration) Refolding 28 Natural selection? Cellular Architecture 29 Cellular Architecture A barrier separating inside from out can give a competitive advantage 29 Cellular Architecture A barrier separating inside from out can give a competitive advantage Keep reactants nearby 29 Cellular Architecture A barrier separating inside from out can give a competitive advantage Keep reactants nearby High local concentrations 29 Cellular Architecture A barrier separating inside from out can give a competitive advantage Keep reactants nearby High local concentrations Protection from the environment 29 RNA world 30 RNA world Nucleic acid: Information & Function 30 RNA world Nucleic acid: Information & Function Lipid bilayer membranes 30 RNA world Nucleic acid: Information & Function DNA Lipid bilayer membranes Information 30 RNA world Nucleic acid: Information & Function DNA Proteins Lipid bilayer membranes Information Function 30 RNA world Nucleic acid: Information & Function DNA Proteins RNA Lipid bilayer membranes Information Function 30 Some time passes... 32 Prokaryotes Typically unicellular Many sizes and shapes, 1-10 µm Cell membrane (and often wall) separates from outside Normally no internal membranes, DNA is in the cytoplasm Despite lack of compartmentalization, internal organization within cytoplasm 33 Endosymbiotic Hypothesis Lynn Margulis 34 Endosymbiotic Hypothesis Lynn Margulis 34 Endosymbiotic Hypothesis Lynn Margulis 34 Endosymbiotic Hypothesis Lynn Margulis 34  April 2024 Science evidence for a nitrogen- xing organelle derived from bacteria “Nitroplast” fi Eukaryotes 37  Eukaryotes Internal membranes form compartments - organelles Metabolism - mitochondria, chloroplasts Synthesis of cellular components - ER, golgi Nuclear envelope encloses DNA Uni- or multi-cellular 10-100 µm in diameter 38 Three Evolutionary Domains 39 Three Evolutionary Domains Snapshot, not endpoint: Evolution is ongoing! 39 Three Evolutionary Domains Dec 2013 Snapshot, not endpoint: Evolution is ongoing! 39  Evolution Evolution doesn’t have a goal (and the goal is NOT us) 40  Evolution Evolution doesn’t have a goal (and the goal is NOT us) 40  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 fi  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 http://coupons.org/pages/bananas/ fi  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 http://coupons.org/pages/bananas/ fi  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 http://coupons.org/pages/bananas/ fi  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 http://coupons.org/pages/bananas/ fi  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 http://coupons.org/pages/bananas/ fi  Evolution Genetic diversity (variation) allows the selection of more t individuals in response to a changing environment 41 http://coupons.org/pages/bananas/ fi  Evolution Past evolution determines what is possible - more complex structures emerge from simpler ones. 42  Evolution Past evolution determines what is possible - more complex structures emerge from simpler ones. 42 http://www.talkdesign.org/faqs/ agellum.html fl  Evolution Evolution is ongoing - as we see with COVID 43 Size Scales in Biology 44 Size Scales in Biology 44 Size Scales in Biology 44 Today’s Learning Objectives Be able to summarize the early stages of chemical evolution Explain the role of complementarity and self-replication Explain the selective advantage conferred by compartmentalization Use the endosymbiotic hypothesis to explain evolution of cell types Differentiate between the evolutionary domains of life Understand the role evolution plays today Explain why past changes constrain future evolution 45