Ch 1 Biochem: Foundations of Biochemistry - Comprehensive Notes
1. Cellular Foundations
Life on Earth arose around 4 billion years ago with simple microorganisms that:
extracted energy from chemical compounds and sunlight
used that energy to synthesize biomolecules from Earth's surface elements and compounds
Principle 1: Cells are the fundamental unit of life
cells vary in complexity and specialization but share remarkable similarities
examples include single-celled bacteria to highly specialized cells in multicellular organisms
Principle 2: Cells use a relatively small set of carbon-based metabolites
these metabolites build polymeric machines, supramolecular structures, and information repositories
the chemical structure of these components defines cellular function
the collection of molecules carries out a program, whose end result is replication of the program and self-perpetuation of the molecule collection (i.e., life)
Principle 3: Living organisms exist in a dynamic steady state, never at equilibrium
follow the laws of thermodynamics by extracting energy from surroundings to maintain homeostasis and do useful work
essentially all cellular energy comes from electron flow, driven by sunlight or metabolic redox reactions
Principle 4: Cells can precisely self-replicate and self-assemble using genome-stored chemical information
example: a single bacterial cell in sterile nutrient medium can yield ~10^9 identical daughter cells in 24 hours; each cell faithfully copies the original via genetic information
on a larger scale, vertebrate progeny resemble parents due to inheritance of parental genes
Principle 5: Living organisms change over time by gradual evolution
results in enormous diversity related through shared ancestry
molecular evidence is seen in the similarity of gene sequences and protein structures
What is biochemistry?
biochemistry = describes the structures, mechanisms, and chemical processes shared by all organisms
1.1 Cellular Foundations
Cells are the structural and functional units of all living organisms
The Plasma Membrane
defines the periphery of the cell
composed of lipid and protein molecules
thin, flexible, hydrophobic barrier around the cell
contains embedded transport proteins, receptor proteins, and membrane enzymes
Cytoplasm Contains Cytosol and Suspended Particles
cytoplasm = internal volume enclosed by the plasma membrane
composed of cytosol (an aqueous solution) plus suspended particles (mitochondria, chloroplasts, ribosomes, proteasomes, etc.)
cytosol = highly concentrated solution containing enzymes, RNA, amino acids, nucleotides, metabolites, coenzymes, and inorganic ions
Clicker Question 1: Cytosol does not contain which? A) enzymes and RNA molecules that encode them; B) membranous organelles (e.g., mitochondria); C) inorganic ions (K+, Na+, Mg2+); D) intermediates in biosynthetic/degradative pathways
Answer: B (membranous organelles sediment when cytoplasm is centrifuged at 150,000 g; the supernatant is the cytosol)
The Nucleoid or Nucleus of a Cell Stores the Genome
genome = complete set of genes, composed of DNA
bacteria/archaea (prokaryotes) store genome in a nucleoid
eukaryotes store genome in a membrane-enclosed nucleus
Cellular Dimensions Are Limited by Diffusion
typical sizes: animal/plant cells 5–100 μm; unicellular microbes 1–2 μm
upper size limit set by transport rate and O2 delivery to all parts of the cell
example: human lymphocytes
Clicker Question 2: All cells: A) have a plasma membrane. B) have mitochondria. C) are approximately the same size. D) are at least partially aerobic.
Answer: A (All cells have a plasma membrane; mitochondria are specific to many but not all cells; size varies; aerobic capacity varies)
Clicker Question 2, Response: All cells have a plasma membrane; the membrane defines cell periphery and serves barrier/interaction roles
Organisms Belong to Three Distinct Domains of Life
Bacteria: inhabit soils, surface waters, and tissues of other organisms
Archaea: inhabit extreme environments
Eukarya: all eukaryotic organisms; more closely related to archaea than to bacteria
Phylogeny of the Three Domains of Life
Archaea and Bacteria Subgroups Are Distinguished by Habitats
aerobic: plentiful O2; energy from electron transfer to O2
anaerobic: no O2; electrons transferred to nitrate, sulfate, or CO2
obligate anaerobes die in O2
facultative anaerobes can live with or without O2
Clicker Question 3: New organism in a salt lake that can live with or without O2 would be best classified as: A) obligate anaerobe in Bacteria; B) obligate anaerobe in Archaea; C) facultative anaerobe in Archaea; D) facultative anaerobe in Bacteria
Answer: C (facultative anaerobe in Archaea)
Clicker Question 3, Response: Archaea inhabit extreme environments; facultative anaerobes can live with or without O2; thus, facultative anaerobe in Archaea
Principle 3 (2 of 5): Reiteration of dynamic steady state; energy from surroundings; electrons flow from light or redox reactions
Organisms Differ Widely in Their Sources of Energy and Biosynthetic Precursors
phototrophs: trap and use sunlight
chemotrophs: derive energy from oxidation of chemical fuels
autotrophs: synthesize all biomolecules directly from CO2
heterotrophs: require preformed organic nutrients from other organisms
Classifying Organisms by Energy Source
Clicker Question 4: Humans are which type? A) photoautotrophs; B) chemoautotrophs; C) photoheterotrophs; D) chemoheterotrophs
Answer: D (humans are chemoheterotrophs): derive energy from chemical fuels and require organic nutrients from others
Clicker Question 4, Response: Humans are chemoheterotrophs; explanation
Bacteria and Archaeal Cells Share Features but Differ in Important Ways
cell envelope: comprised of plasma membrane, outer membrane, and peptidoglycan (high-molecular-weight polymer)
Bacterial and Archaeal Cell Envelopes
Gram-positive bacteria: thick peptidoglycan layer outside plasma membrane; no outer membrane; Gram stain positive
Gram-negative bacteria: outer membrane is a lipid bilayer
Archaea: layer of peptidoglycan or protein provides rigidity
Principle 2 (2 of 6): Small metabolite set to build cellular machines; program and self-replication
The E. coli Cytoplasm
contains ribosomes, enzymes, metabolites, cofactors, inorganic ions
nucleoid contains a single, circular DNA molecule
plasmids: smaller circular DNA segments that confer toxin/antibiotic resistance
Eukaryotic Cells Have Various Membranous Organelles (isolated for study)
mitochondria: site of most energy-extracting reactions
endoplasmic reticulum and Golgi: synthesize and process lipids and membrane proteins
peroxisomes: oxidize very-long-chain fatty acids and detoxify reactive oxygen species
lysosomes: digestive enzymes
granules/droplets: store nutrients (e.g., starch, fat)
Clicker Question 5: Which organelle is not membrane-bound? A) lysosome B) peroxisome C) ribosome D) Golgi complex
Answer: C (ribosome is not membrane-bound)
Clicker Question 5, Response: Ribosome is not membrane-bound; others are enclosed by membranes
Plant Cell Organelles
vacuoles: store large quantities of organic acids
chloroplasts: site of light-driven ATP synthesis (photosynthesis)
Eukaryotic Cell Structure
Clicker Question 6: Which organelle is found in both plant and animal cells? A) starch granule B) chloroplast C) mitochondria D) glyoxysome
Answer: C (mitochondria)
Clicker Question 6, Response: Mitochondria are present in both plant and animal cells
Activity: Metabolic Map
guided exploration of metabolic pathways; focus on shared pathways among prokaryotes and eukaryotes
Activity Instructions (1 of 4)
Think of three pathways and determine if they are used by eukaryotes, prokaryotes, or both; discuss in pairs and class
Activity Solution (1 of 4)
Prokaryotes: Glycolysis, Gluconeogenesis, Citric Acid Cycle, Glycogen metabolism, Urea cycle, Oxidative phosphorylation, etc.; Both: many core pathways
Subcellular Fractionation of Tissue
first step: gently disrupt cells/tissues to rupture plasma membrane
second step: centrifuge the homogenate
organelles differ in size and sedimentation rates
The Cytoplasm Is Organized by the Cytoskeleton and Is Highly Dynamic
cytoskeleton = three-dimensional network of protein filaments in eukaryotic cells
components: actin filaments, microtubules, intermediate filaments
filaments continually disassemble and reassemble
Cytoskeletal Filaments: actin filaments, microtubules, chromosomes, kinetochores, centrosomes, intermediate filaments
The Structural Organization of the Cytoplasm
endomembrane system segregates specific metabolic processes and provides surfaces for enzyme-catalyzed reactions
Exocytosis and endocytosis = transport across membranes; involve membrane fusion/fission; connect cytoplasm with surroundings
Clicker Question 7: The cytoskeleton is composed of: A) membranous organelles. B) kinetochores and centrosomes. C) actin filaments, microtubules, and intermediate filaments. D) chromosomes and plasmids.
Answer: C; the cytoskeleton comprises actin filaments, microtubules, and intermediate filaments
Clicker Question 7, Response: Correct—three general cytoplasmic filament types
Principle 2 (3 of 6): Small metabolite set to build cellular machines; life program
Cells Build Supramolecular Structures
held together by noncovalent interactions: hydrogen bonds, ionic interactions, van der Waals interactions, hydrophobic effect
In Vitro Studies May Overlook Important Interactions Among Molecules
in vitro = in glass; in vivo = in living organism
molecules may behave differently in vivo vs. in vitro
Clicker Question 8: Supramolecular complexes (e.g., chromatin) are held together by: A) covalent bonds between monomeric units. B) noncovalent interactions (e.g., hydrogen bonds). C) covalent bonds between macromolecules. D) interactions between cytoskeleton and organelles
Answer: B; noncovalent interactions hold supramolecular complexes together
Clicker Question 8, Response: Noncovalent interactions drive chromatin organization; monomer covalent bonds join subunits, not the supramolecular assembly
1.2 Chemical Foundations
Elements Essential to Animal Life and Health
Biomolecules Are Carbon-based Compounds with Functional Groups
carbon forms covalent single, double, and triple bonds
Geometry of Carbon Bonding
carbon atoms adopt a characteristic tetrahedral arrangement for four single bonds
free rotation around single bonds; limited rotation about double bonds
Common Functional Groups of Biomolecules
Additional Functional Groups of Biomolecules
Clicker Question 9: Important functional groups in biomolecules include: A) lipids. B) thioesters. C) nucleic acids. D) carbons.
Answer: B; thioesters are a notable functional group in biomolecules
Clicker Question 9, Response: Thioesters confer specific chemical properties; functional groups define families of compounds
Many Biomolecules Are Polyfunctional
Cells Contain a Universal Set of Small Molecules
central metabolites: common amino acids, nucleotides, sugars and their phosphorylated derivatives, mono-/di-/tricarboxylic acids
secondary metabolites: organism-specific
metabolome = entire collection of small molecules in a cell under certain conditions
metabolomics = systematic characterization of the metabolome under precise conditions
Macromolecules Are Major Constituents of Cells
macromolecules = polymers with MW > ~5,000 built from simple precursors
major classes: proteins, nucleic acids, polysaccharides
oligomers = shorter polymers
informational macromolecules = proteins, nucleic acids, some oligosaccharides with information-rich subunits
Protein Macromolecules
proteins are long polymers of amino acids; functions include enzymes, structural components, signal receptors, transporters
proteome = all proteins functioning in a cell; proteomics = study of this protein set
Clicker Question 10: Proteins are macromolecules because: A) they can noncovalently form large structures. B) they are polymers with MW above ~5,000. C) they can function as enzymes, structural elements, receptors, or transporters. D) they are composed of multiple oligomers.
Answer: B; proteins are macromolecules because they are polymers with MW > ~5,000
Clicker Question 10, Response: Correct—the definition of macromolecules includes high molecular weight polymers
Nucleic Acid Macromolecules
DNA and RNA = polymers of nucleotides; store and transmit genetic information; some RNA have structural/catalytic roles
genome = entire sequence of a cell's DNA or RNA
genomics = characterization of genome structure, function, evolution, and mapping
Polysaccharide Macromolecules
polysaccharides = polymers of simple sugars; roles in energy storage, cell-wall structure, and intercellular recognition
glycome = entire repertoire of carbohydrate-containing molecules
Lipid Molecules
lipids = water-insoluble hydrocarbon derivatives; roles include membrane structure, energy stores, pigments, intracellular signaling
lipidome = lipid-containing molecules in a cell
Activity: Classifying Metabolites
explore structure of palmitic acid in Mol3D viewer
Activity Instructions (2 of 4)
Is palmitic acid a carbon-based metabolite? What type of biomolecule is palmitic acid?
Activity Solution (2 of 4)
Palmitic acid is carbon-based (backbone with 16 carbons) and is a fatty acid, a type of lipid
Building Blocks of Biochemistry
Major Classes of Biomolecules in E. coli Cells (Table 1-1)
Water ~70% of weight; Proteins ~15% (≈3,000 species); DNA ~1% (1–4 molecules); RNA ~6% (>3,000 species);
Polysaccharides ~3%; Lipids ~2%; Monomeric subunits and intermediates ~2%; Inorganic ions ~1%Note: if all fatty acid permutations are counted, lipid diversity is vast
Clicker Question 11: The systematic characterization of the entire collection of small molecules in a given cell under a specific set of conditions is called: A) genomics. B) proteomics. C) lipidomics. D) metabolomics.
Answer: D; metabolomics
Clicker Question 11, Response: Metabolomics = study of the metabolome under defined conditions
Three-Dimensional Structure Is Described by Configuration and Conformation
configuration = fixed spatial arrangement of atoms
stereoisomers = molecules with same bonds and formula but different arrangement
stereospecific = interactions require specific conformations
Illustrating Stereochemistry
Configurations of Geometric Isomers
cis/trans (geometric) isomers differ in substituent arrangement around double bonds
Chiral and Achiral Molecules
chiral centers = stereocenters with four different substituents
a molecule can have 2^n stereoisomers where n = number of chiral centers
Clicker Question 12: Molecules that differ in configuration cannot be: A) stereoisomers. B) cis-trans isomers. C) chiral centers that are mirror images of each other. D) chiral centers that can be interchanged by rotation of a single bond.
Answer: D; chiral centers that can be interconverted by rotation of a single bond are not distinct stereoisomers
Clicker Question 12, Response: Configuration depends on double bonds or chiral centers; rotation around single bonds can interconvert conformers but not alter configuration
Enantiomers and Diastereomers
enantiomers = mirror-image stereoisomers
diastereomers = non-mirror-image stereoisomers
Optical Activity of Enantiomers
enantiomers have similar reactivity but different optical activity
racemic mixture shows no net optical rotation
Naming Stereoisomers Using the RS System
assign priorities to groups attached to chiral carbon
priority order example: —OCH3 > —OH > —NH2 > —COOH > —CHO > —CH2OH > —CH3 > —H
Clicker Question 13: Enantiomers: A) are only associated with amino acids. B) can be specific types of diastereomers. C) are always designated either D or L. D) can exist for molecules with more than one chiral carbon.
Answer: D; enantiomers can exist for molecules with more than one chiral carbon
Clicker Question 13, Response: Enantiomers can arise when there are multiple chiral centers; each can yield distinct stereoisomers
Molecular Conformation
conformation = spatial arrangement of substituent groups that are free to rotate
Principle 2 (4 of 6): Small metabolite set to build polymeric and supramolecular structures
Interactions Between Biomolecules Are Stereospecific
Biological Systems Can Distinguish Stereoisomers
stereospecificity = ability to distinguish stereoisomers
Clicker Question 14: The antidepressant Celexa is a racemic mixture of two stereoisomers, but only (S)-citalopram has the therapeutic effect. A stereochemically pure preparation of (S)-citalopram is sold as Lexapro. Which is true? A) Lexapro shows no optical activity. B) Biological systems cannot distinguish the two isomers. C) The effective dose of Lexapro is half that of Celexa. D) Both stereoisomers are biologically active.
Answer: C (Lexapro’s active enantiomer allows a lower dose to achieve the therapeutic effect)
Clicker Question 14, Response: Only the active enantiomer contributes to efficacy; racemate requires higher total dose for effect
1.3 Physical Foundations
Living organisms exist in a dynamic steady state, never at equilibrium with surroundings
small molecules, macromolecules, and supramolecular complexes are continually synthesized and broken down
steady state requires constant energy input
Organisms Transform Energy and Matter from Surroundings
system vs. universe definitions; open/closed/isolated systems
open systems exchange both energy and matter with surroundings
Clicker Question 15: A living organism is a(n): A) isolated system. B) closed system. C) open system. D) universe.
Answer: C; open system
Clicker Question 15, Response: Open system exchanges energy and matter with surroundings
Energy Transformation in Living Organisms
first law of thermodynamics: energy is conserved; can change form
Extracting Energy from Surroundings
photoautotrophs vs chemotrophs
Oxidation-Reduction Reactions
redox reactions involve transfer of electrons; linked to energy flow in metabolism
autotrophs/heterotrophs participate in global O2/CO2 cycles powered by sunlight
Creating and Maintaining Order Requires Work and Energy
second law: total randomness tends to increase; living systems maintain order by inputting energy
entropy S measures randomness/disorder
Free Energy, G
enthalpy H ≈ heat content
free energy G = H − T S
in a closed system, G predicts work potential and spontaneity
Clicker Question 16: Which reflects the total energy change in a chemical reaction, i.e., bonds formed/broken? A) ∆G B) ∆H C) ∆S D) ∆T
Answer: B; ∆H
Clicker Question 16, Response: Enthalpy change ∆H reflects bond energies and noncovalent interactions broken/formed
Free-Energy Change, ∆G
spontaneous reactions have riangle G < 0
for reactions in a closed system, reactions proceed toward equilibrium until ∆G = 0
Coupling Reactions
endergonic reactions can be driven by coupling to exergonic reactions (e.g., ATP hydrolysis)
breaking phosphoanhydride bonds in ATP is highly exergonic
Energy Coupling Links Reactions in Biology
in closed systems, reactions proceed spontaneously until equilibrium; in living systems, coupling maintains non-equilibrium states
Clicker Question 17: If A → B has ∆G = −14 kJ/mol and C → B has ∆G = +16 kJ/mol, then: A) A→C reversible. B) A→C exergonic. C) A and C can never be at equilibrium. D) A→C is entropically driven.
Answer: B; A→C is exergonic (∆G = −30 kJ/mol if combined)
Clicker Question 17, Response: Demonstrates that combining reactions can yield a larger exergonic drive
Keq and ∆G° as Measures of Spontaneity
Keq = ([products]eq)/([reactants]eq) at equilibrium
Mass-Action Ratio, Q = [products]/[reactants] at any time; used to gauge distance from equilibrium
relation: riangle G = riangle G^ of the reaction? + RT \,
standard free-energy change, ∆G°, is the free energy change under standard conditions; actual ∆G depends on concentrations
Mass-Action Ratio, Q
Q = ([A]^{a} [B]^{b} …)/([C]^{c} [D]^{d} …)
Clicker Question 18: ATP breakdown yields ADP and Pi; Keq = 2×10^5 M. With cellular [ATP] = 15 mM, [ADP] = 1.5 mM, [Pi] = 15 mM, is this reaction at equilibrium in living cells?
Answer: D; No, because Q ≪ Keq. Calculation: Q = [ADP][Pi]/[ATP] = (1.5 mM)(15 mM)/15 mM = 1.5 mM, far from Keq
Clicker Question 18, Response: Q is much smaller than Keq; reaction far from equilibrium in cells
Standard Free-Energy Change, ∆G°
∆G actual for a reaction depends on ∆G° and conditions: riangle G = riangle G^\u00b0 + RT \, ext{ln} Q
details: A reaction with ∆G° and actual conditions yields current ∆G
Clicker Question 19: A reaction will always be thermodynamically spontaneous if: A) ∆H < 0 and ∆S > 0. B) ∆G = 0. C) it is coupled to another reaction. D) ∆G° > 0.
Answer: A (and due to coupling as needed); spontaneous when ∆G < 0
Clicker Question 19, Response: Spontaneity requires ∆G < 0; A combines negative enthalpy and positive entropy contributions
Reactions Do No Work at Equilibrium
Reaction Coordinate Diagrams and Enzymes
exergonic reactions can be coupled to endergonic reactions to drive processes toward biological work
enzymes greatly increase reaction rates by stabilizing transition states
Activation energy: riangle G^\u00b0
Enzymes do not change the equilibrium, only the rate
Clicker Question 20: What function do enzymes perform? A) Increase equilibrium. B) Increase rate but not equilibrium. C) Increase activation energy. D) Make products higher energy than reactants.
Answer: B; enzymes increase rate without altering equilibrium
Clicker Question 20, Response: Enzymes are biocatalysts; lower activation energy, raise rate; do not affect equilibrium
Catabolism and Anabolism
Pathways are sequences of consecutive reactions where product of one becomes substrate of next
Catabolism: degradative, energy-yielding; drives ATP synthesis and NAD(P)H production
Anabolism: synthetic pathways requiring energy input
Metabolism
metabolism = network of enzyme-catalyzed pathways (both catabolic and anabolic)
unity of life: core pathways acting on proteins, fats, sugars, nucleic acids are largely identical across organisms
Metabolism Is Regulated to Achieve Balance and Economy
Feedback inhibition: slows production by inhibiting catalytic activity when product accumulates
Systems biology: quantifies complex interactions among intermediates and pathways
Clicker Question 21: Feedback inhibition does what? A) contains the overall network. B) inhibits enzyme activity to slow product formation. C) is a sequence of consecutive reactions. D) increases production of intermediates.
Answer: B; feedback inhibition reduces enzyme activity to balance production
Clicker Question 21, Response: Inhibits catalytic activity to maintain balance in metabolic networks
Activity: Metabolic Map
further exploration of pathways and reactions in Achieve course
Activity Instructions (3 of 4)
address what drives electron flow to obtain energy; glycolysis energy source
Activity Solution (3 of 4)
redox reactions drive electron flow; ATP breakdown fuels endergonic steps
Bonus Discussion
identify intersections and shared intermediates; consider how changes in one pathway affect others
2. Chemical Foundations
Elements essential to animal life and health
Biomolecules are carbon-based with diverse functional groups
carbon forms single, double, and triple bonds; carbon skeletons define molecule properties
Geometry of carbon bonding
tetrahedral arrangement for four single bonds; free rotation around singles; limited rotation about double bonds
Common functional groups of biomolecules
Additional functional groups of biomolecules
Clicker Question 9: Important functional groups include: A) lipids. B) thioesters. C) nucleic acids. D) carbons.
Answer: B; thioesters are a notable functional group
Clicker Question 9, Response: Functional groups confer chemical properties; thioesters are one example
Polyfunctional biomolecules
Universal small molecules in cells
central metabolites: amino acids, nucleotides, sugars and phosphorylated derivatives, etc.
secondary metabolites: organism-specific
metabolome/metabolomics: study of small-molecule complement
Macromolecules are major cellular constituents
macromolecules = polymers > ~5,000 Da; major classes: proteins, nucleic acids, polysaccharides
oligomers = shorter polymers
informational macromolecules = proteins, nucleic acids, certain oligosaccharides with information-bearing sequences
Protein macromolecules
proteins = polymers of amino acids; functions include enzymes, structural roles, receptors, transporters
proteome/proteomics = protein complement & its study
Clicker Question 10: Proteins are macromolecules because: A) form large structures noncovalently. B) they are polymers with MW > ~5,000. C) they function as enzymes, structural elements, receptors, or transporters. D) they are composed of multiple oligomers.
Answer: B; MW > ~5,000 defines macromolecules
Clicker Question 10, Response: Correct
Nucleic acid macromolecules
DNA and RNA = polymers of nucleotides; store/transmit genetic information; some RNAs have structural/catalytic roles
genome = complete DNA/RNA sequence
genomics = genome structure/function/evolution/mapping
Polysaccharide macromolecules
polymers of simple sugars; roles include energy stores, cell-wall components, extracellular recognition
glycome = carbohydrate-containing molecules in a cell
Lipid molecules
lipids = hydrophobic hydrocarbons; roles include membranes, energy stores, pigments, signaling
lipidome = lipid-containing molecules in a cell
Activity: Classifying Metabolites
Palmitic acid structure exploration
Activity Instructions (2 of 4)
Determine if palmitic acid is carbon-based metabolite; what type of biomolecule is it?
Activity Solution (2 of 4)
Palmitic acid is carbon-based (16 carbons); it is a fatty acid, i.e., a lipid
Building Blocks of Biochemistry (reprise of major biomolecule classes)
Major Biomolecule Classes in E. coli (Table 1-1; percentages by weight)
Water ~70%
Proteins ~15% (~3,000 species)
Nucleic acids: DNA ~1%; RNA ~6% (~3,000+ species)
Polysaccharides ~3%; Lipids ~2%
Monomeric subunits and intermediates ~2%; Inorganic ions ~1%
Note: lipid diversity is enormous when considering fatty acid permutations
Clicker Question 11: The systematic characterization of the entire collection of small molecules in a cell under defined conditions is called: A) genomics. B) proteomics. C) lipidomics. D) metabolomics.
Answer: D; metabolomics
Clicker Question 11, Response: Metabolomics studies the metabolome under specified conditions
Three-Dimensional Structure: configuration and conformation
configuration = fixed spatial arrangement of atoms
stereoisomers = same bonds/formula, different arrangement
stereospecificity = interaction depends on conformation
Geometric isomers (cis/trans)
Chiral and Achiral molecules
chiral centers (asymmetric carbon)
a molecule with n chiral centers can have 2^n stereoisomers
Clicker Question 12: Molecules that differ in configuration cannot be: A) stereoisomers. B) cis-trans isomers. C) chiral centers that are mirror images. D) chiral centers that can be interchanged by rotation of a single bond.
Answer: D; rotation around a single bond can interconvert conformers, not configuration
Clicker Question 12, Response: Configuration vs. conformation distinction clarified
Enantiomers and diastereomers
enantiomers = mirror-image stereoisomers
diastereomers = non-mirror-image stereoisomers
Optical activity of enantiomers
enantiomers have similar reactivities but differ in optical rotation
racemic mixture shows no net optical rotation
RS naming for stereoisomers
priorities assigned to substituents; example ordering given in class notes for priority
Clicker Question 13 (summary): Enantiomers can exist for molecules with more than one chiral carbon
Answer: D; enantiomers exist when there are one or more chiral centers
Clicker Question 13, Response: D is correct; stereoisomerism arises from multiple chiral centers
Molecular Conformation
conformation = spatial arrangement of freely rotating substituents
Principle 2 (4 of 6) and related: re-emphasize the small set of metabolites and modular assembly of cellular structures
Interactions Between Biomolecules Are Stereospecific
Biological Systems Distinguish Stereoisomers
stereospecificity defined; biological recognition often enantioselective
1.4 Genetic Foundations
Principle 4 (2 of 5): DNA stores information; precise replication and assembly guided by genome
bacterial replication can yield billions of identical daughter cells; vertebrate inheritance follows parental genes
Principle 2 (6 of 6) (reiteration for cross-reference)
Genetic Information Is Encoded in DNA
DNA = deoxyribonucleic acid; sequence of deoxyribonucleotides
encode instructions to form cellular components; provide a template to produce identical DNA
Genetic Continuity Is Vested in Single DNA Molecules
E. coli genome: single molecule ~4.64 million nucleotide pairs
replication must be near-perfect to yield identical progeny
The Structure of DNA Allows Replication and Repair with Near-Perfect Fidelity
deoxyribonucleotides = monomers of DNA
complementary base pairing across strands via hydrogen bonds
strands held together by hydrogen bonds; not covalent bonds between strands
Clicker Question 22: Which statement about DNA is false? A) DNA is a double helix of two polymeric strands. B) Each strand serves as a template for copying. C) Covalent interactions between complementary bases occur between strands. D) Deoxyguanylate is complementary to deoxycytidylate.
Answer: C; covalent interactions do not occur between complementary bases across strands; hydrogen bonds (noncovalent) do
Clicker Question 22, Response: The strands are held by hydrogen bonds (noncovalent); covalent bonds link bases to sugars within each strand
The Linear Sequence in DNA Encodes Proteins with 3D Structures
native conformation = precise 3D shape of a protein essential for function
Clicker Question 23: The DNA sequence of a gene for a protein:
A) is a nonlinear code. B) mutates at a high rate. C) ultimately determines the amino acid sequence of a protein. D) is a polymer of four ribonucleotides.
Answer: C; DNA sequence determines the amino acid sequence via transcription to RNA and translation
Clicker Question 23, Response: C is correct; the linear DNA sequence maps to a protein sequence which folds into a functional conformation
Activity: Relating Terms within the Chapter
concept map exercise to connect terms such as each cell, genomic information, precise self-replication, inheritance, etc.
Activity Instructions (4 of 4)
construct a concept map linking the listed terms
Activity Solution (4 of 4)
pair up to discuss variations and connections
3. Physical Foundations
Living organisms exist in a dynamic steady state, never at equilibrium; energy required to maintain order
Systems vs. Universe: open systems exchange both energy and matter with surroundings
Energy transformation in living systems
first law: energy conserves; energy changes form
second law: entropy tends to increase; local order maintained by energy input
Free energy and spontaneity
free energy change ∆G determines spontaneity; if ∆G < 0, reaction is spontaneous
relation: ∆G = ∆H − T∆S; where ∆H is enthalpy, ∆S is entropy
standard free energy change ∆G° and the actual ∆G depend on concentrations via:
Enzyme-catalyzed reactions
enzymes accelerate reactions by lowering activation energy (ΔG‡) without changing the overall equilibrium
reaction coordinate diagrams illustrate exergonic and endergonic steps and coupling
activation energy:
Coupling and Energy Transduction
ATP hydrolysis as a major exergonic driver for endergonic processes
energy coupling enables cellular work
Clicker Question 20 (review): Enzymes increase reaction rates but not equilibrium; answer B
Clicker Question 16 (review): Enthalpy change ∆H reflects bonds formed/broken
Clicker Question 15 (review): Open system for living organisms
Metabolic organization and regulation
metabolism = network of catabolic and anabolic pathways
flow of electrons (redox) powers energy capture and biosynthesis
catabolic → ATP, NAD(P)H production; anabolic uses energy for synthesis
Regulation via feedback inhibition
feedback inhibition maintains balance of intermediate production and utilization
systems biology approach to quantify interactions among pathways
Conceptual points for 1.3 Physical Foundations
reaction coupling is central to metabolism
free energy and disequilibrium enable biological work
4. Genetic Foundations
Principle 4 (2–5 of 5): Precise replication and assembly using genome information
bacteria: a single cell can give rise to many identical cells; vertebrates show resemblance across generations due to inheritance
Genetic Information Is Encoded in DNA
DNA = sequence of deoxyribonucleotides; code for forming cellular components
DNA provides a template to replicate identical DNA molecules
Genetic Continuity in Single DNA Molecules
E. coli genome size ~4.64 million base pairs in a single circular chromosome
faithful replication is essential for identical progeny
The Structure of DNA and Replication/Repair Fidelity
deoxyribonucleotides are the monomeric subunits; base pairing is complementary across strands via hydrogen bonds
strands are held together by hydrogen bonds; covalent bonds connect bases to the sugar-phosphate backbone within each strand
The Linear Sequence in DNA Encodes Proteins with 3D Structures
native conformation = precise 3D structure of a protein
DNA sequence encodes the amino acid sequence of a protein via RNA intermediate; protein folds into structure guided by sequence
Mutations and genetic variation
mutations alter nucleotide sequence and can affect cellular components; not all mutations are beneficial
The RNA role in prebiotic evolution (context)
RNA can act as catalyst and information repository; potentially first genes/catalysts
Miller–Urey experiments (context of origin of biomolecules)
simulated early-Earth conditions; energy sources included electrical sparks mimicking lightning
produced amino acids, hydroxy acids, aldehydes
false statement in quiz: A) energy provided by boiling the liquid phase is false; energy came from electrical sparks
The First Cell and Energy Sources (prebiotic evolution)
protocells formed from lipid vesicles containing self-replicating RNA
protocells with higher replication capacity became more numerous
Early energy sources for primitive cells
inorganic fuels (e.g., ferrous sulfide, ferrous carbonate)
photosynthesis later evolved; led to O2 in the atmosphere
Eukaryotic cells evolved from simpler precursors in stages
major changes: chromosome evolution, nucleus evolution, endosymbiotic events with aerobic/ photosynthetic bacteria
Endosymbiosis and mitochondria
eukaryotic mitochondria originated via symbiosis with ancient bacteria
mitochondria are integral to aerobic metabolism in modern eukaryotes
Evolutionary relationships revealed by molecular anatomy
homologs = proteins that share sequence similarity across organisms
sequence similarity informs phylogenetic relationships
Functional genomics and genomic organization
genes grouped by cellular processes; housekeeping genes expressed constitutively; regulatory genes modulate expression
differences in regulatory gene content contribute to organism complexity
Genomics and medicine
large-scale sequencing identifies genes linked to conditions; proteins encoded by these genes are drug targets
Clicker Question 25: Eukaryotic cells: A) first appeared about 3.5 billion years ago. B) obtained mitochondria via symbiotic bacteria. C) are similar to Archaeal cells in most respects. D) preceded the development of a double-membrane surrounding DNA.
Answer: B; mitochondria originated via endosymbiosis with an ancient bacterium
Clicker Question 25, Response: Endosymbiotic origin explains mitochondria presence in eukaryotes
Clicker Question 26: Genome sequencing showed that differences in human genes between individuals are relatively small; overall gene content is highly conserved across humans
Answer: D; sequencing shows few differences in genes between individuals, highlighting unity of life at molecular level
Activity: Evolution – Muddiest Point (1 of 2 and 2 of 2)
student activities to reflect on evolution concepts and clarify points of confusion
Summary points
molecular evolution connects genetic variation to phenotypic diversity
endosymbiosis is a key driver of eukaryotic complexity
5. Evolutionary Foundations
Principle 5 (2–3 of 3): Living organisms change over time by gradual evolution
vast diversity arises from shared ancestry; molecular evidence visible in gene/protein similarity
Changes in Hereditary Instructions Allow Evolution
mutation = changes in DNA sequence; can alter cellular components; may be beneficial or detrimental
wild type = unmutated baseline
Biomolecules First Arose by Chemical Evolution
Miller–Urey experiments showed plausible pathways to biomolecules from simple precursors under early-Earth conditions
The Role of RNA in Prebiotic Evolution
RNA could act as catalyst and information store; may have preceded DNA/proteins in early life
RNA or Precursors as First Genes and Catalysts
alternative scenarios include metabolic-first pathways or RNA-based systems
Miller–Urey experiments – false/true statements reviewed (context for exam)
false statement example: energy source not boiling; energy from electrical sparks
Biological Evolution Began > 3.5 Billion Years Ago
protocells with self-replicating RNA and lipid vesicles led to protocell lineages with replication advantage
First Energy Sources
early cells likely used inorganic fuels; photosynthesis evolved later to produce O2
Eukaryotic Cells Evolved via Endosymbiosis
mitochondria and chloroplasts trace to endosymbiotic events; nucleus evolution also pivotal
Molecular Anatomy Reveals Evolutionary Relationships
homologs across species indicate common ancestry; gene/protein sequence similarity reveals phylogeny
Genomic Comparisons in Medicine
genome sequencing identifies disease-associated genes; potential drug targets emerge from understanding gene function
Key Takeaways for Evolutionary Foundations
unity of life: despite diversity, core biomolecular machinery is conserved
evolution acts on variation via mutation and selection
endosymbiosis transformed prokaryotic cells into eukaryotes, enabling complex life