Lehninger Chapter 1 - The Foundations of

Biochemistry

Biochemistry with Lab (Johns Hopkins University)

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Chapter 1 - The Foundations of Biochemistry
○ Feature of living organisms
■ High degree of chemical complexity and microscopic organization
■ Systems for extracting, transforming, and using energy from environment
■ Capacity for precise self replication and self assembly
■ Mechanisms for sensing and responding to alterations in their surroundings
■ Defined functions for each of components and regulated interactions among them
■ History of evolutionary change
1.1 Cellular Foundations
● Cells are Structural and Functional Units of All Living Organisms
○ Plasma membrane - defines periphery of cell, separating its contents from its surroundings
■ Composed of lipid and protein molecules that form thin, tough, pliable,
hydrophobic barrier around cell
■ Transport proteins in plasma membrane allow passage of certain ions and molecules
■ Receptor proteins transmit signals into cell
■ Membrane enzymes participate in reaction pathways
■ Cell division (fission) occurs to produce 2 cells
■ Cytoplasm - composed of aqueous solution, cytosol, and other particles;
internal volume bounded by plasma membrane
● Cytosol - highly concentrated solution containing enzymes and RNA
molecules that encode them, components (AA and nucleotides) from which
these macromolecules are assembled, 100s of small organic molecules
(metabolites) which are intermediates in biosynthetic and degradative
paths, coenzymes, inorganic ions, and ribosomes (small particles made of
protein and RNA molecules) which are site for protein synthesis
○ All cells have nucleus or nucleoid in which the genome is stored and replicated
■ In bacteria, nucleoid is not separated from cytoplasm by a membrane
● Prokaryotes
■ In higher organisms, nucleus consists of nuclear materials enclosed within double
membrane (nuclear envelope)
● Eukaryotes
● Cellular Dimensions are Limited by Oxygen Diffusion
■ Animal and plant cells are typically 5 to 100 um in diameter
■ Bacterial cells are typically only 1 to 2 um long
○ Lower limit: set by minimum number of each type of biomolecule required by cell
○ Upper limit: rate of diffusion of solute molecules in aqueous systems; specifically,
oxygen intake is limited since cell’s surface-to-volume ratio decreases as cell size
increases
● There are Three Distinct Kingdoms / Domains of Life
■ Prokaryotes
● Archaebacteria - inhabit extreme environments (salt lakes, hot springs,
highly acidic bogs, ocean depths)
● Eubacteria - inhabit soils, surface waters, and tissues of other living
or decaying organisms
■ Eukaryotes
● Eukarya - evolved from same branch of Archae
○ Environments
■ Aerobic - plentiful supply of oxygen
■ Anaerobic - virtually devoid of oxygen; organisms adapted by obtaining
energy though transferring electrons to nitrate (=N2), sulfate (=H2S), or
CO2 (=CH4)
● Obligate anaerobes - organism that die when exposed to oxygen
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○ Energy Sources
■ Phototrophs- trap and use sunlight for energy
● Autotrophs - can obtain all needed carbon

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 ● Heterotrophs - require organic nutrients to obtain carbon
■ Chemotrophs - derive energy from oxidation of a fuel; require source of
organic nutrients; cannot fix CO2 into organic compounds
● Lithotrophs - fuels they oxidize are inorganic
● Organotrophs - fuels they oxidize are organic
● Escherichia coli Is the Most Studied Prokaryotic Cell
○ [Link] is normally harmless inhabitant of human intestinal tract
○ 2 um long and little less than 1 um in diameter
○ Has protective outer membrane and inner plasma membrane that encloses cytoplasm and
nucleoid
■ Peptidoglycans are polymers found between inner and outer membrane →
give shape and rigidity to cell
● In archaebacteria, pseudopeptidoglycans give cell shape and rigidity
○ Cell envelope - constitute plasma membrane and layers outside PM
○ Plasmids - smaller, circular segments of DNA
■ Highly flexible in manipulation since they can confer resistance to toxins and
antibiotics in environment
● Eukaryotic Cells Have Variety of Membranous Organelles, Which Can Be Isolated for Study
○ Size: 5 to 100um in diameter; cell volumes thousand to million times larger than bacteria
○ Features: nucleus and variety of membrane-bounded organelles with specific functions
■ Mitochondria, ER, Golgi complexes, lysosomes
■ Plant cells also have vacuoles and chloroplasts
○ Techniques: Differential centrifugation (organelles are separated through different
buoyant densities) and Isopycnic (same density) centrifugation

● Cytoplasm is Organized by Cytoskeleton and is Highly Dynamic

○ Cytoskeleton - protein filaments within eukaryotic cells which differ in width,
composition, and specific function; provide structure and organization to cytoplasm and
shape to cell
■ Actin filaments, microtubules, intermediate filaments
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● Actin filaments and microtubules also help with movement

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 ■ Locations are not permanent and can be disassembled / reassembled often
■ Interactions between cytoskeleton and organelles are noncovalent, reversible,
and subject to regulation in response to intracellular / extracellular signals
○ Endomembrane system - segregates specific metabolic processes and provinces
surfaces on which certain enzyme catalyzed reactions occur
○ Exocytosis and endocytosis - mechanisms of transport that involve membrane fusion and
fission, providing paths between cytoplasm and surrounding medium, allowing for
secretion of substances, and uptake of extracellular materials
● Cells Build Supramolecular Structures
○ Level 4: Cell and its organelles
○ Level 3: Supramolecular complexes - ex. Chromosome, plasma membrane, cell wall;
macromolecules are held together by noncovalent interactions (weaker than covalent
bonds individually)
■ Hydrogen bonds (between polar groups)
■ Ionic interactions (among nonpolar groups)
■ Hydrophobic interactions (among nonpolar groups in aqueous solution)
■ Van der Waals
○ Level 2: Macromolecules - ex. DNA, protein, cellulose
○ Level 1: Monomeric units - ex. Nucleotides, amino acids, sugars; joined by covalent bonds
● In Vitro Studies May Overlook Important Interactions among Molecules
○ In vitro - in glass /test tube; without interference from other molecules present in intact cell
○ In vivo - in living
1.2 Chemical Foundations
○ 4 most abundant elements in living organisms: Hydrogen, Oxygen, Nitrogen, and Carbon
⇒ make up more than 99% of mass of most cells
■ Lightest elements which form the strongest bonds
○ Trace elements have negligible weight in human body, but serve essential roles (i.e. 4
iron ions used for oxygen transporting capacity)
● Biomolecules are COmpounds of Carbon with Variety of Functional Groups
○ Carbon accounts for more than ½ the dry weight of cells ⇒ can form single bonds
with H atoms, and both single and double bonds with O and N atoms
■ Form very stable carbon-carbon single bonds
○ Functional groups - confer specific chemical properties on molecule; groups of other
atoms attached to C
■ C is only chemical element that can form such a wide variety off different sized
and shaped molecules with variety of functional groups
■ Alcohols - one or more hydroxyl groups (OH)
■ Amines - amino groups
■ Aldehydes and ketones - carbonyl groups
■ Carboxylic acids - carboxyl groups

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● Cells Contain a Universal Set of Small Molecules
○ In cytosol, there is collection of 100 to 200 different small organic molecules which
are polar, water soluble, and present in micromolar to millimolar concentrations
○ Secondary metabolites - plants contain; play role specific to plant life which give off
specific scents
○ Metabolome - entire collection of small molecules in given cell
● Macromolecules are Major Constituents of Cells
○ Macromolecules - polymers of high molecular weight assembled from relatively simple
precursors
■ Proteins - long polymers of amino acids which constitute largest fraction of cells
(besides water); most versatile of biomolecules
■ Nucleic acids - DNA and RNA; polymers of nucleotides; store and transmit genetic
info
■ Polysaccharides - polymers of simple sugars; functions as energy yielding fuel
storage and extracellular structural elements with specific binding sites for
proteins
● Oligosaccharides - shorter polymers of sugars; serve as specific cellular
signals
■ Lipids - hydrocarbon derivatives; serve as structural components of membranes,
energy rich fuel stores, pigments, and intracellular signals; not considered
macromolecular in size
○ Informational macromolecules - characteristic information rich subunit sequence; i.e.
proteins and nucleic acids
● Three Dimensional Structure is Described by Configuration and Conformation
○ Stereoisomers - molecules with same chemical bonds but different
stereochemistry (different configuration)
■ Configuration - fixed spatial arrangement of atoms
● Conferred by presence of double bonds (no freedom of rotation) or
chiral centers (substituent groups are arranged in specific sequence)
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○ Geometric isomers - cis/trans; differ in arrangement of substituent
groups with respect to nonrotation double bond
■ Cis - on this side; groups on same side of double bond
■ Trans - across; groups on opposite sides

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 ○ Chiral centers - asymmetric carbon; when carbon atom has 4 different
substituent groups attached which can never superimpose upon the
mirror image of the original molecule
■ Molecules with one chiral carbon can have two stereoisomers
■ When two or more (n) chiral carbons are present, there
can be 2n stereoisomers
● Enantiomers - stereoisomers that are mirror images of
each other
○ Have nearly identical chemical properties but
differ in characteristic physical property
(interaction with plane- polarized light)
○ Equimolar solution of 2 enantiomers (racemic
mixture), shows no optical rotation
● Diastereomers - stereoisomers that are not mirror
images of each other
■ Compounds without chiral centers do not rotate plane of plane
polarized light
○ Achiral - when tetrahedral carbon has only 3 different groups (one
group occurs twice); molecule is superimposable on its mirror image
■ Conformation - spatial arrangement of substituent groups that (without breaking
any bonds) are free to assume different position in space BC of freedom of rotation
about single bonds
● Staggered - more stable than all others and predominates
● Eclipsed - least stable
○ Stereospecific - require specific stereochemistry in interacting molecules
○ Nomenclature
■ For compounds with more than one chiral center, use RS system → groups
attached to chiral carbon are assigned priority
○ -OCH2 > -OH > -NH2 > -COOH > -CHO > -CH2OH > -CH3 > -H
● Chiral atom is viewed with group of lowest priority pointing away from viewer
○ If the priority of the other 3 groups decrease in clockwise order, the
configuration is (R) for rectus or right
○ If the priority of the other 3 groups decrease in counterclockwise
order, the configuration is (S) for sinister or left
■ D and L system - molecule with single chiral center
● Interactions between Biomolecules are Stereospecific
○ In living organisms, chiral molecules are usually present in only one of chiral forms
depending on what is available in nature
○ Stereospecificity - ability to distinguish between stereoisomers; property of enzymes and
other proteins and characteristic feature of molecular logic of living cells
1.3 Physical Foundations
○ Storage and expression of information require energy → cells have developed highly
efficient mechanisms for coupling energy obtained from sunlight or fuels to many
energy consuming processes they must carry out
● Living Organisms Exist in Dynamic Steady State, Never at Equilibrium with Their Surroundings
○ Population of molecules within organisms are dynamic → small molecules,
macromolecules, and supramolecular complexes are continuously synthesized and
then broken down in chemical rxns which involve a constant flux of mass and
energy through system
○ Dynamic steady state - constancy of concentration; requires constant investment of energy
● Organisms Transform Energy and Matter from Their Surroundings
○ System - all reactants and products present, solvent that contains them, and immediate
atmosphere; everything within defined region of space
■ Isolated -when a system does not exchange matter or ts surroundings
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 ■ Closed - when a system exchanges energy but not matter with its surroundings
■ Open - when a system exchanges both energy and matter with its surroundings
○ Universe - system and its surrounding together
○ Living organisms are open systems, exchanging both matter and energy with their
surroundings
■ They derive energy from their surroundings by 1) taking up chemical fuels from
environment and extracting energy by oxidizing fuels, or 2) absorbing energy
from sunlight
○ 1st law of thermodynamics - i nay physical or chemical change, total amount of
energy in universe remains constant, although form of energy may change
● Flow of Electrons Provides Energy for Organisms
○ Nearly all living organisms service energy from radiant energy of sunlight (via
direct or indirect methods) which arises from thermonuclear fusion reaction
carried out in sun
■ Photosynthetic cells absorb light energy and use it to drive electrons from
water to CO2, forming energy rich products like glucose (C6H12O6), starch,
and sucrose → releasing O2 into atmosphere
■ Nonphotosynthetic cells and organisms obtain energy by oxidizing energy rick
products of photosynthesis and passing electrons to atmospheric O2 to form
water, carbon dioxide, and other end products
○ Oxidation-reduction reactions - reactions involving electron flow; where one reactant is
oxidized (loses electrons) as another is reduced (gains electrons)
● Creating and Maintaining Order Requires Work and Energy
○ 2nd law of thermodynamics - total entropy of universe is continuously increasing
○ Free energy is required to bring order to synthesizing macromolecules from monomeric
units
■ Entropy, S - randomness or disorder of components of chemical system
● Change to Entropy (ΔS) is always positive
■ Gibb’s Free Energy Constant, G - in closed systems
● ΔG = ΔH - T ΔS
● Process tends to occur spontaneously only if ΔG is negative
● Cell function depends on molecule for which free energy of formation is
positive (molecules ar eless stable and more highly ordered than mix of
monomeric components)
○ Endergonic - energy requiring rxns that are considered less
favorable; cells couple them to other rxns that liberate free
energy
○ Exergonic - reactions that liberate free energy
● Overall, the process is exergonic and sum of free energy change is negative
● Ex. Energy released by hydrolysis of phosphoanhydride bonds
■ Enthalpy, H - reflects number and kinds of bonds
■ T - absolute temperature (in Kelvin)
● Energy Coupling Links Reactions in Biology
○ Issue of bioenergetics is the means by which energy from fuel metabolism or light capture
is coupled to cell’s energy requiring reactions
○ Amount of energy available to do work is free energy change, ΔG
○ In closed systems, chemical reactions proceed spontaneously until equilibrium is reached
→ rate of product formation exactly equals rate at which product is converted to reactant
■ In spontaneous reactions, products have less free energy than reactants →
reaction releases free energy which is available to do work (exergonic
reactions)
■ Endergonic reaction require input of energy and ΔG is positive
● Keq and ΔG° are Measures of Reaction’s Tendency to Proceed Spontaneously
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○ Equations: aA + bB → cC + dD
■ Keq = ([Ceq]c [Deq]d) / ([Aeq]a [Beq]b)
● Large Keq means the reaction tends to proceed until reactants have
been almost completely converted into products
○ Standard free energy change, ΔG° - constant that is characteristics of each specific reaction
■ ΔG = ΔG° + RT ln([Ci]c [Di]d) / ([Ai]a [Bi]b)

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 ● Gas constant, R
● Absolute temperature, T
■ When reaction reaches equilibrium, no driving force remains and it can do no work;
ΔG = 0 and [Ai] = [Aeq]
● ΔG° = -RT ln(Keq)
● ΔG° and ΔG are measured in joules per mole
○ When Keq >>1, ΔG° is large and negative
○ When Keq <<1, ΔG° is large and positive
● Enzymes Promote Sequences of Chemical Reactions
○ All biological macromolecules are much less thermodynamically stable than their
monomeric subunits, yet are kinetically stable
■ Uncatalyzed breakdown occurs so slowly that these molecules are stable
○ Enzymes - biocatalysts that greatly enhance rate of specific chemical reactions
without being consumed in process
■ Activation barrier - energy barrier from the reactants to products; must be
surmounted to produce reaction
● Breaking of existing bonds and formation of new ones requires distortion
of existing bonds (transition state)
■ Activation energy, ΔG‡ - difference in energy between reactant in its ground
state and in its transition state
● Binding of enzyme to transition state is exergonic, and every released by
this binding reduces activation energy for reaction and greatly increases
reaction rate
○ 2 or more reactants can bind to enzyme’s surface close to each other and with
stereospecific orientations that favor reaction
○ Cellular catalysts are mainly proteins → multiplicity of enzymes, specificity (ability to
discriminate between reactants), and susceptibility to regulation give cells
capacity to lower activation barriers selectively
■ Catabolism - pathways that lead to degradation and free energy yielding
reactions; phase of intermediary metabolism concerned with energy yielding
degradation of nutrient molecules
■ Anabolism - pathways that require input of energy; phase of intermediary
metabolism concerned with energy requiring biosynthesis of cell components from
smaller precursors
■ Metabolism - network of enzyme catalyzed pathways
● ATP is major link (intermediate) between catabolic and anabolic components
of network
● Metabolism is Regulated to Achieve Balance and Economy
○ Feedback inhibition - keeps production and utilization of each metabolic intermediate in
balance
1.4 Genetic Foundations
○ Deoxyribonucleic acid, DNA - genetic material; sequence of monomeric subunits,
nucleotides, in linear polymer encodes instructions for forming all other cellular
components and provides template for production of identical DNA molecules to be
distributed to progeny when cell divides
● Genetic Continuity is Vested in Single DNA Molecules
○ DNA is long, thin, organic polymer
○ Sperm and egg carry accumulated hereditary information, transmit inheritance in
form of DNA molecules, and are then encoded
● Structure of DNA Allows for Its Replication and Repair with Near Perfect Fidelity
○ Deoxyribonucleotides - basic unit of DNA; linear polymer of four different
monomeric subunits, deoxyribonucleotides, arranged in precise linear sequence

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■ Sequence then encodes genetic info
■ 2 of polymeric strands are twisted about each other to form DNA double helix
where deoxyribonucleotides from both strands pair up together and serve as
template for synthesis of new complementary strand, generating 2 identical
double helical molecules, one for each daughter cell
■ One strand is kept for repair of damage on other strand

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 ● Linear Sequence in DNA ENcodes Proteins with 3D Structures
○ One to 3D dimensions occurs in 2 phases - 1) linear sequence of deoxyribonucleotides in
DNA codes (through intermediary, RNA) for production of protein with corresponding
linear sequence of AAs, 2) protein folds into 3D shape, determined by its AA sequence
and stabilized by noncovalent interactions
■ Native conformation - precise 3D structure of protein; crucial for function
■ Once in native conformation, protein can associate noncovalently with other
proteins or nucleic acids or lipids, to form supramolecular complexes
■ Correct folding also requires correct environmental conditions - pH, ionic
strength, metal ion concentrations, etc
1.5 Evolutionary Foundations
● Changes in Hereditary Instructions Allow Evolution
○ Mutation - infrequent, unrepaired mistakes in DNA replication process that leads
to changes in nucleotide sequence of DNA; changes instructions for some cellular
component
○ Wild type - unmutated cells in population
● Biomolecules First Arose by Chemical Evolution
○ Organic compounds, including basic biomolecules like AAs and carbohydrates, are
found in only trace amounts of earth’s crust, the sea, and the atmosphere → how did
first organisms acquire these organic building blocks?
○ Earth may have had methane, ammonia, and water in atmosphere, devoid of
oxygen → reducing atmosphere
■ Electrical energy from lightning discharges or heat energy from volcanoes
caused these compounds of primitive atmosphere to react to form simple
organic compounds → dissolved in ancient seas which eventually became rich
with organic substances
■ In the ocean, some organic molecules had greater tendency to interact with
other to create larger complexes → assembled spontaneously to form
membranes and catalysts (enzymes) which came together to form earliest cells
● Chemical Evolution can be Simulated in Laboratory
○ Experiment with gas mixtures of NH3, CH4, H2O, and H2 + electrical sparks → gas
CO and CO2 + starting materials
■ Water contained variety of organic compounds (AAs, hydroxy acids, aldehydes, and
HCN)
● RNA or Related Precursors May Have Been First Genes and Catalysts
○ Since RNA can act as catalysts in own formation, this suggests that RNA or similar
molecule may have been first gene and first catalyst
■ Creation of prebiotic soups, including nucleotides → production of short RNA
molecules with random sequences → selective replication of self duplicating
catalytic RNA segments → Synthesis of specific peptides, catalyzed by RNA →
increasing role of peptides in RNA replication → primitive translation system
develops → genomic RNA begins to be copied into DNA → DNA genome,
translated on RNA protein complex (ribosome) with protein catalysts
● BIological Evolution Began More than Three and a Half Billion Years Ago
○ Earth formed about 4.5 billion years ago and 1st evidence of life dates to more than
3.5 billion years ago
● First Cell was Probably a Chemoheterotroph
○ Organic compounds required at the time were synthesized from components of early
atmosphere (CO, CO2, N2, CH4, etc) by non biological actions of volcanic heat and
lightning
■ Eventually acquired ability to derive energy from compounds in environment and
to use that energy to synthesize more of own precursor molecules, becoming
less dependent on outside sources
■ Original donor for photosynthetic processes was H2S, yielding elemental sulfur or
sulfate (SO4 2-) as byproduct

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 ● Later, cells developed enzymatic capacity to use H2O as electron
donor in photosynthetic reactions, eliminating O2 as waste
○ Cyanobacteria
○ Earliest cells were anaerobic (didn’t need oxygen)
■ Chemoheterotrophs could oxidize organic compounds to CO2 by passing
electrons not to O2 but to acceptors like SO4 2-, yielding H2S as product
■ Atmosphere then became progressively ricker in oxygen → aerobic
organisms started to proliferate
■ Aerobes obtained energy by passing electrons from fuel molecules to
oxygen → releases great deal of energy
● Bacteria
● Eukaryotic Cells Evolved from Prokaryotes in Several Stages
○ 1.5 billion years ago → 3 major changes occurred to create eukaryotes
■ 1) As cells acquired more DNA, mechanism required to fold it compactly into
discrete complexes with specific proteins and to divide it equally between
daughter cells at cell division became more elaborate
● Chromosomes stabilize folded DNA and pull DNA protein complexes apart
during cell division
■ 2) As cells became larger, system of intracellular membranes developed,
including double membrane surrounding DNA which segregated nuclear
process of RNA synthesis on DNA template from cytoplasmic process of protein
synthesis on ribosomes
■ 3) Early eukaryotic cells enveloped aerobic bacteria or photosynthetic
bacteria to form endosymbiotic associations that became permanent
● Some aerobic bacteria evolvedi nto mitochondria and some
photosynthetic cyanobacteria became plastids (ex. chloroplasts)
■ Unicellular organisms found it advantageous to cluster together → increased
motility, efficiency or reproductive success than free living single celled
competitors
→ led to permanent associations
● Cellular specialization led to evolution of more complex and highly
differneitated organisms in which some cells carried out sensory
functions, others digestive, photosynthetic, or productive functions
● Molecular Anatomy Reveals Evolutionary Relationships
○ Genome - complete genetic endowment of organism
■ Homologs - proteins encoded by homologous sequences of genes (when 2 genes
share readily detectable sequence similarities)
● If occurring in same species, they are said to be paralogous and protein
products are paralogs
○ Evolved out of gene duplication followed by gradual changes in
sequences of both copies
○ Commonly found to have same sequence and same 3D structure
→ different functions
● Two homologous genes occurring in different species are considered
orthologous, and proteins products are orthologs
○ Commonly found to have same function in both organisms
○ Annotated genome - includes DNA sequence and a description of likely function of each
gene product, deduced from comparisons with other genomic sequences and established
protein functions
■ Larger number of sequence differents, the earlier the divergence in evolutionary
history
● Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes
○ After annotated genomes are archived, we can group genes according to processes
(DNA synthesis, protein synthesis, generation of ATP, etc) and functions
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 ○ More complex an organism is, the greater the proportion of its genome encodes genes
invovledi n regulation of cellular processes and smaller proportion dedicated to basic
processes themselves (ATP generation and protein synthesis)
● Genomic Comparisons will have Increasing Importance in Human Biology and Medicine
○ Genomes of chimps and humans are 99.9% identical, yet there is clear difference in
intelligence, physicality, communication, etc.
○ Similarly, though the difference in genome among humans is incredibly small,
there are clearly differences that are visible in health, susceptibility to disease,
etc.

Summary
1.1Cellular Foundations
- All cells are bound by plasma membrane; have cytosol containing metabolites, coenzymes,
inorganic ions, and enzymes; and set of genes contains with either nucleoid (prokaryotes) or
nucleus (eukaryotes)
- Phototrophs use sunlight for energy; chemotrophs oxidize fuels, passing electrons to good
electron acceptors (inorganic components, organic compounds, molecular oxygen)
- Bacterial cells contain cytosol, nucleoid, and plasmids
- Eukaryotic cells have nucleus amd are multicompartmental, segregating certain
processes in specific organelles
- Cytoskeletal proteins assemble into long filaments that give cells shape and rigidity and serve
as rails along which cellular organelles move throughout cell
- Supramolecular complexes are held together by noncovalent interactions and for hierarchy of
structures
- When molecules are removed to be studied in vitro, we can lose essential
interactions between molecules we would see in vivo
1.2Chemical Foundations
- BC of bonding versatility, carbon can produce broad array of carbon-carbon skeletons with
variety of functional groups → groups give biomolecules their biological and chemical
properties
- Nearly universal set of several 100 small molecules is found in living cells →
interconversion of these molecules in central metabolic paths have been conserved in
evolution
- Protein and nucleic acids are linear polymers of simple monomeric subunits → sequences
contain info that gives each molecule its 3D structure and biological functions
- Molecular configuration can be changed only by breaking covalent bonds
- For carbon atom with 4 different substituents (chiral carbon), substituent groups
can be arranged in 2 different ways, generating stereoisomers with distinct
properties → only 1 stereoisomer is biologically active
- Molecular conformation is position of atoms in space that can be changed by rotation about
single bonds, without breaking covalent bonds
- Interactions between biological molecules are almost invariably stereospecific - require
complementary match between interaction molecules
1.3Physical Foundations
- Living cells are open systems, exchanging matter and energy with their surroundings,
extracting and channeling energy to maintain themselves in dynamic steady state
distant from equilibrium
- Energy is obtain from sunlight by converting energy from electron flow into chemical bonds
of ATP
- Tendency for chemical reaction to proceed toward equilibrium is expressed as free energy
change, ΔG, which has 2 components: enthalpy change, ΔH, and entropy change, ΔS

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 - ΔG = ΔH - T ΔS
- When ΔG is negative, reaction is exergonic and tends to go toward completion
- When ΔG is positive, reaction is endergonic and tends to go in reverse direction
- Conversion of ATP to Pi and ADP is highly exergonic (large negative ΔG), and many
endergonic cellular reactions are driven by coupling them to reaction

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 - Standard free energy change for reaction, ΔG° , is a physical constant that is related to
equilibrium constant by
- ΔG° = -RT ln(Keq)
- Most exergonic cellular reactions proceed at useful rates only BC enzymes are present to catalyze
them
- Enzymes act by stabilizing transition state, reducing activation energy, ΔG‡, and
increasing reaction rate by several orders of magnitude
- Metabolism is sum of many interconnected reaction sequences that interconvert cellular
metabolites
- Each sequence is regulated to provide what cell needs at given time and to expend
energy only when necessary
1.4Genetic Foundations
- Genetic info is encoded in linear sequence of 4 deoxyribonucleotides in DNA
- Double helical DNA molecule contains internal template for its own replication and repair
- Linear sequence of AAs in protein, which is encoded in DNA of gene for protein, produces
protein’s unique 3D structure
- Individual macromolecules with specific affinity for other macromolecules self assemble into
supramolecular complexes
1.5Evolutionary Fundations
- Occasional inheritable mutations yield organism that is better suited for survival in
ecological niche and progeny that are preferentially selected
- Basis for Darwinian evolution that led from first cell to all organisms that now exist,
and it explains fundamental similarity of all living organisms
- Life originated about 3.5 billion years ago, most likely with formation of membrane enclosed
compartment containing self replicating RNA molecule
- Components for first cell were produced by action of lightning and high
temperature on simple atmospheric molecules likes CO2 and NH3
- Catalytic and genetic roles of early RNA genome were separated over time, with DNA
becoming genomic material and proteins the major catalytic species
- Eukaryotic cells acquired the capacity for photosynthesis and for oxidative phosphorylation from
endosymbiotic bacteria
- In multicellular organisms, differentiated cell types specialize in one or more of
functions essential to organism’s survival
- Knowledge of complete genomic nucleotide sequences fo organisms from different branches of
phylogenic tree provides insights into evolution and function of extant organisms and offers
great opportunities in human medicine

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