CELL BIOLOGY © Gerald Karp, John Wiley and Sons | Chapter 1
Molecular Biology of the Cell  Superoxide dismutase (SOD) – an enzyme that destroys
Chapter 2
The Structure and Functions of Biological Molecules
2.1 Covalent Bonds
 Covalent Bonds – bonds b/n atoms w/ shared pairs of e-
o Principle: an atom is most stable when its outermost
electron shell is filled
o requires 80–100 kilocalories to break a mole of
covalent bonds
 Molecules – stable combinations of atoms held together
by covalent bonds
o Compounds – molecules w/ 2+ type of atom
2.2 Noncovalent Bonds
 Type of Covalent Bonds – determines the shape of the
molecule
o Single Bond – involves one pair of electrons
o Double bond – involves two pairs or electrons
o Triple Bond – involves 3 pairs of electrons
 Electronegativity
o Bonded atoms with same electronegativity = equally
shared electron pairs
o Bonded atoms with diff. electronegativity – shared e-
is closer to the atom w/ greater electronegativity
 Depends upon the number of protons in nucleus
2.1.1 Polar and Nonpolar Molecules
 Polar molecules – have asymmetric distributions of
electrical charge (dipole)
o Polar molecule of biological importance contains one
or more electronegative atom (N,O,S)
 Nonpolar molecules – lack polarized bonds &
electronegative atoms (C&H)
o Waxes and fat – large non polar molecules
 proteins and phospholipids – have both polar and
nonpolar regions
2.1.2 Ionization
 Ions – result when strongly electronegative nuclei capture
electrons
o Anions – have extra electrons
o Cations – have lost electrons
The Human Perspective: Free Radicals as a Cause of Aging

-
Free radicals – unstable atoms/molecules w/ unpaired e
o formed during normal metabolism
 When a covalent bond is broken such that each
portion keeps ½ of the shared electrons
 When only single e- is accepted during redox rxn
o highly reactive & damage macromolecules (i.e. DNA)
o May play a role in aging
.–
the superoxide radical (O2 )
o protects cells from damage due to the superoxide
radical
o extends the life span of laboratory animals that
overproduce it
o superoxide radical (O2.–) – a type of free radical
-
formed when molecular oxygen picks up an extra e
 Hydrogen peroxide (H2O2) – potentially reactive oxidizing
agent
o can break down to form hydroxl radicals that attack
the cell’s macromolecules
o catalase or gluthaione peroxidise – destroys H2O2
 Noncovalent bonds – weaker linkages that govern the
interactions b/n molecules
o Weak bonds – play an important role in dynamic
cellular processes
 readily broken and re-formed
 1-5 kcal/mol
o depend on attractive forces b/n atoms having an
opposite charge
 Types of Noncovalent Bonds
o Ionic Bonds
o Hydrogen bonds
o Hydrophobic interaction and van de Waals forces
2.2.1 Ionic Bonds: Attractions Between Charged Atoms
 Ionic bonds – attractions between charged atoms
o weakened in the presence of water
o may be significant within large biological molecules
2.2.2 Hydrogen Bonds
 Hydrogen bonds – occurs when covalently bound
hydrogen has a partial positive charge and attracts
electrons of a second atom
o determine the structure and properties of water
o occur in biological molecules (i.e., b/n DNA strands)
2.2.3 Hydrophobic Interactions and van der Waals Forces
 Hydrophobic Interaction and van de Waals forces:
o occur when nonpolar molecules associate and
minimize their exposure to polar molecules.
o van der Waals forces or attractions b/n nonpolar
molecules – due to transient dipole formation
 operate at optimum distances
 maximized by complementary surfaces
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2.2.4 Life Supporting Properties of Water  Biological processes are sensitive to pH

o Changes in pH affect the ion state and function of
 structure of water is suitable for sustaining life proteins
o highly asymmetric – both H atoms are on one side o Buffers – compounds in living systems that react with
o Both covalent O–H free hydrogen or hydroxyl ions → resist changes in pH
bonds are highly  Usually contains weak acid + conjugate base
polarized  bicarbonate ions and carbonic acid buffer the
o All 3 atoms readily blood:
form H-bonds

Hydrogen bond formation between

neighboring water molecules.
Each H atom of the molecule has about
four-tenths of a full positive charge, and
the single O atom has about eight-tenths
of a full negative charge

 properties of water result from its structure

o requires a lot heat to evaporate
o excellent solvent for many substances 2.4 Nature of Biological Molecules
o determines the interactions b/n biological solutes
 Carbon – central to the chemistry of life
2.3 Acids, Bases and Buffers o forms 4 covalent bonds, with itself or other atoms
 carbon atoms can be linked together to form the
backbones of a virtually unlimited variety of
 Protons – not only found in the atomic nuclei, they are
organic molecules
also released into the medium whenever an H atom loses
o biochemicals – carbon-containing molecules
a shared electron
produced by living organisms
o Acetic acid – distinctive ingredient of vinegar
 Undergoes dissociation
Cholesterol – structure
CH3COOH → CH3COO- + H+ illustrates how carbon atoms
Acetic Acid Acetate Ion Proton (H Ion)
are able to form covalent bonds
o Protons released does not remain in the free state – it
with as many as four other
combines with other molecules carbon atoms
 Combination with a water molecule
H+ + H2 O → H3 O + Carbon backbone of a
Proton (H Ion) water molecule Hydronium Ion cholesterol molecule includes
 Combination with a hydroxyl Ion four rings, which is
H+ + OH- → H2 O characteristic of steroids (e.g.,
Proton (H Ion) Hydroxyl Ion water molecule
estrogen, testosterone, cortisol)
 Combination with an amino group in a protein
H+ + --NH2 → --NH3+  Hydrocarbons – contain only carbon and hydrogen
Proton (H Ion) Amino Group Charged Amine
o Vary in the number of carbons, and the number of
 Acids, Bases & Amphoterics double and triple bonds between carbons
o Acids – release protons
o Bases – accept protons 2.4.1 Functional Groups
o Amphoteric molecules – can act as acids or bases
 Functional groups—groups of atoms giving organic
molecules different characteristics and properties (physical
properties, chemical reactivity, solubility in aq. solution)

 Acids and Bases exist in pairs

CH3COOH → CH3COO- + H+
Acetic Acid Acetate Ion H Ion
Acid Conjugate Base

--NH2 + H+ → --NH3+ Most contains one or more electronegative atoms (N,P,O, and/or S) – makes organic
Amino Group Proton (H Ion) Charged Amine molecules more polar, water soluble and more reactive
Base Conjugate Acid

 2 most Common Linkages b/n FG

 pH scale – measures acidity
o Ester bonds – forms b/n carboxylic acids and alcohols
o pH = –log [H+]
o Amide Bonds – forms b/n carboxylic acids and amines
o ion product constant for water:
Kw = [H+][OH–] = 10-14 at 25 °C
+ –
o As [H ] increases, [OH ] decreases so that the
–14
product equals 10

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2.4.2 Classification of Biological Molecules by Function
 Macromolecules – huge, highly organized molecules that
the form the structure and carry out the activities of cells
o Perform complex task with precision and efficiency
o Four major categories:
 Proteins polymers – composed of large
 Nucleic Acids number of low-molecular-weight
 Polysaccharides building blocks, monomers
 Lipids
 Building Blocks of Macromolecules
o Macromolecules w/in a cell have a short lifetime
compared w/ the cell itself (excpt DNA)
 continually broken down and replaced
o low-molecular-weight precursors
 amino acids → Proteins
 nucleotides → Nucleic Acids
 sugars → Polysaccharides
 fatty acids incorporated into Lipids
 Metabolic Intermediates (metabolites)
o Metabolic pathways – each series of chemical rxns
o Metabolic intermediates – compounds formed along
the pathways leading to end products that may have
no function
 Molecules of Miscellaneous Function
o Vitamins - adjuncts to proteins
o Steroid or amino acid hormones
o ATP – energy storage
o Cyclic AMP – regulatory molecules
o metabolic waste products (urea)
2.5 Four Types of Biological Molecules
 Carbohydrates – include simple sugars & sugar polymers
 Lipids – a diverse group of nonpolar molecules
o Fats – made of glycerol linked by three ester bonds
to three fatty acids
 Proteins – polymers of amino acids and form a diverse
group of macromolecules
 Nucleic acids are polymers of nucleotides that store and
transmit genetic information
o Deoxyribonucleic acid (DNA)
o Ribonucleic acid (RNA)
CELL BIOLOGY © Gerald Karp, John Wiley and Sons | Chapter 1
2.5.1 Carbohydrates
 Carbohydrates (glycans) – include simple sugars
(monosaccharides) and sugar polymers
o serve as energy storage molecules and durable
building materials for biological construction
o General chemical formula: (CH2O)n
 Sugars important in cellular metabolism (n=3-7)
 Triose – sugar with 3 carbon
 Tetrose – sugar with 4 carbon
 Pentose – sugar with 5 carbon
 Hexose – sugar with 6 carbon
 Heptose – sugar with 7 carbon
 Structure of Simple Sugars
o Each sugar molecule has a backbone of carbon atoms;
each carbon atom is linked to a single hydroxyl grp
excpt for one that has a carbonyl (C=O)
 Ketose sugars – have a carbonyl (C=O) on an
internal carbon
 Aldose sugars – have a carbonyl on a terminal
carbon
o Sugars can be linear but sometimes form ring
structures
 Stereoisomerism
o Asymmetric carbons (Chiral) – bond to 4 diff. groups
 can exist in two mirror-image configurations that
cannot be superimposed
 enantiomers – either D- or L-isomers
 stereoisomers
o Sugars can have many asymmetric carbon
 designated D- or L-
according to the
arrangement around
the carbon farthest
fr the carbonyl grp
o Formation of an alpha- and beta-pyranose
 When a molecule of glucose undergoes self-
reaction to form a pyranose ring (i.e., a six-
membered ring), 2 stereoisomers are generated
 two isomers are in equilibrium with each other
through the open-chain form of the molecule
 alpha-pyranose – OH group of the first
carbon projects below the plane of the ring
 beta-pyranose – OH group projects upward
 Linking Sugars Together
o Glycosidic bonds: –C—O—C– links between sugars
o Disaccharides – source of readily available energy
o Oligosaccharides – found bound to cells surface
proteins and lipids, and may be used for cell
recognition
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o Polysaccharides – polymers of sugars joined by
glycosidic bonds
 Nutritional Polysaccharides
 Glycogen – an animal product made of
branched glucose polymers
 Storehouse of surplus chemical energy
in animals
 Starch – a plant product made of both
branched & unbranched glucose polymers
 Storehouse of surplus chemical energy
in plants
 Amylose + Amylopectin
 Amylose – unbranched helical
 Amylopectin – branched (less
than glycogen)
 Structural Polysaccharides
 Cellulose: plant product made of
unbranched polymers
 Chitin: component of invertebrate
exoskeleton
 Unbranched polymer of N-
acetylglucosamine
 GAGs: composed of two different sugars
and found in extracellular space
 -A-B-A-B-A-B-
 Heparin – inhibits blood coagulation
 Activates antithrombin – inhibitor
of thrombin
2.5.2 Lipids
 Lipids – a diverse group of nonpolar molecules
o Ability to dissolve in organic solvents (i.e. Chloroform,
benzene)
o Inability to dissolve in water
 Fats – made of glycerol linked by three ester bonds to
three fatty acids (FAs)
o FAs – unbranched hydrocarbons w/ 1 carboxyl group
 amphipathic
o Saturated FAs – lack C=C double bonds
 solid at room temperature
o Unsaturated FAs – w/ one or more C=C double bonds
 oils – liquid at room temperature
CELL BIOLOGY © Gerald Karp, John Wiley and Sons | Chapter 1
o Naturally occurring FAs – have DB in cis configuration
 more DB
 less effective they can be packed together
 lowers the melting temperature
 Steroids – built around a characteristic four-ringed
hydrocarbon skeleton
o Cholesterol – a component of animal cell membranes
 Precursor for the synthesis of other steroid
hormones (progesterone, testosterone, estrogen)
 Absent in plant cells
 Phospholipids – resembles a fat (triacylglycerol) but with
only 2 FA chains (Diacylglycerol)
o amphipathic lipids – major component of cell memb.
phospholipid phosphatidylcholine
consists of a glycerol backbone w/
hydroxyl groups covalently
bonded to two fatty acids and
a phosphate group (negatively
charged bonded to a small,
positively charged choline
group)
phosphorylcholine – hydrophilic
fatty acid tail – hydrophobic
2.5.3 Proteins
 Proteins – polymers of amino acids and form a diverse
group of macromolecules
o exhibit a high degree of specificity
o have a variety of cellular functions
 Building Blocks of Proteins
o Amino acids – have an α
carbon, an amine group,
a carboxyl group, and a
variable R group
 in nature occurs as the L stereoisomer
 linked together by peptide bonds into a
polypeptide chain to make a protein
 R groups : polar charged; polar uncharged;
nonpolar
 Chemical Structure of Amino Acids
o 20 amino acids – represent those most commonly
found in proteins and those encoded by DNA
o amino acids are arranged into four groups based on
the character of their side chains
o All molecules are depicted as free amino acids in
their ionized state – exist in solution at neutral pH
 Properties of Side Chains (R Group)
o Polar charged – contain R groups that act as stronger
organic acids, bases; can form ionic bonds
 Almost always fully charged (lysine, arginine,
aspartic acid, glutamic acid) at pH 7
 side chains are strong org. acids & bases
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 form ionic bonds due to charges  Structure of Proteins

 histones w/ arginine (+ charged) bind to (-
charged) phosphate groups of DNA
 Histidine – usually only partially charged at pH 7
 often important in enzyme active sites due
to its ability gain or lose a proton in
physiologic pH ranges
 Primary structure – sequence of AAs in the polymer
o 4 Protein Structure units
 Primary Structure – Sequence
 Secondary Structure – Backbone
 Tertiary Structure – all the atoms
 Quaternary Structure – multiple subunit
o critical to the protein function
o linear; 1 dimensional
o formed by peptide bonds

 Secondary structure – conformation of adjacent AAs into

α-helix, β-sheet, hinges, turns, turns, loops, or finger-like
extensions
o non-linear; 3 dimensional
o Polar uncharged – R groups weakly acidic or basic o formed and stabilized by hydrogen
 not fully charged at pH 7 bonding, electrostatic and van der
 can form H bonds with other molecules like Waals interactions
- +
water – have atoms w/ δ or δ charge o Native Confirmation – w/ biological
 Asparagine & glutamine [amides of aspartic & activity
glutamic acid], threonine, serine, tyrosine  ALL peptide bonds is in TRANS
o 2 most common Secondary Structure
 α-helix
 coil of helix: right-handed
 repeat every 18 residue
 3.6 amino Acid per turn
 110° distance per
amino acid
o Nonpolar – R groups hydrophobic  5.4 Å (.54nm) – repeat
 generally lack O & N distance
 cannot interact with water or form electrostatic  C=O of each peptide bond
bonds is H-bonded to the N-H of
 vary primarily in size & shape the amino acid that is 4
 allows them to pack tightly into protein core residues away – parallel
 Associate with one another via hydrophobic & to the helical axis
van der Waals interactions in protein core  R-groups: pointed outward from the helix
 Alanine, valine, leucine, isoleucine, tryptophan,  β-pleated sheet – pleats result from the location
phenylalanine, methionine of the α -carbons above and below the plane of
the sheet
 3.5 Å – distance along the axis b/n adjacent
residues
 either parallel (in the same N-terminal to C-
terminal direction) or antiparallel (in the
opposite N-terminal to C-terminal direction)
o Glycine, Proline, Cysteine
 R-groups: alternate to one another
 Glycine (R = H) – small R group makes backbone
flexible & able to move; useful in protein hinges
 allows 2 backbones (of same or different
protein) to approach closely
 Proline – forms ring w/ amino grp (imino acid)
 hydrophobic amino acid – does not readily
fit into orderly secondary structure (a-helix)
 Cysteine – R group has reactive —SH  Tertiary structure – conformation of entire polymer
 forms disulfide (—S—S—) bridge with o stabilized by
other cysteines often at some distance noncovalent bonds
away in polypeptide backbone o studied by X-ray
crystallography
o final level of
structure for
proteins consisting
of only 1 polypeptide
chain
o Proteins can be fibrous
or globular

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o Myoglobin – first globular proteins whose tertiary
structure was determined
 Stores oxygen in muscle cells
The Human Perspective: Protein Misfolding Can Have Deadly
 heme prosthetic group – binds O2
 Quaternary structure – proteins w/ subunits
o manner in which
subunits interact
o held together by
intermolecular R group
interactions
o 2 kinds:
 Homotypic –
identical or nearly
identical subunit
 Heterotypic – very different subunits
 Additional Structural Characteristics
o Protein Domains – occur when proteins are
composed of two or more distinct regions
 Each domain is a functional region
o Dynamic Changes within Proteins
 May occur with protein activity
 Conformational changes – non-random
movements triggered by the binding of a specific
molecule
 Protein-Protein Interactions
o multiprotein complex – different physically
associated proteins
o Can be studied using the yeast two-hybrid (Y2H)
o Results from large-scale studies can be presented in
the form of a network
o A list of potential interactions can be used to
elucidate unknown processes
o Hub proteins most likely more important that non-
hub proteins
 Protein Folding – process that occurs in various steps
o Anfinsen – observed that unfolding is due to
denaturation, brought about by various agents
 Removal of denaturing agents could lead to
refolding
o Denaturation – loss of structural order
 Unfolding due to the disruptions of interactions
between subunits; Loss of biological activity
 Causes of Denaturation
 Heat – disrupts non covalent bonds by
increasing collisions b/n molecules (3°, 4°)
 pH – disrupts electrostatic bond by altering
the side chains (2°,3°, 4°)
 Detergents (sodium dodecylsulfate) –
disrupt hydrophobic interactions (2°,3°, 4°)
 Urea/Guanidine – disrupt H-bond (2°,3°, 4°)
 Mercapthoethanol – disrupt disulfide bond
(3°, 4°) – Anfinsen Experiment
o Two alternate pathways for protein folding:
 Proteins may assume their native conformation
through a series of steps
 Proteins may fold along pathways without
intermediate forms
 Smaller proteins with single domains fold faster
than larger proteins with multiple domains
CELL BIOLOGY © Gerald Karp, John Wiley and Sons | Chapter 1
Consequences
 Creutzfeld-Jakob Disease (CJD) – results from misfolded
protein in the brain
o PrPc – normal protein in healthy brains
o PrPSc – in CJD brain which is identical or similar to PrPc
but is misfolded
 Also causes “Mad cow disease”, kuru, & scrapie
 Alzheimer’s disease (AD) – involves misfolded proteins
that accumulate in the brains of affected individuals
o amyloid precursor protein (APP) – membrane-bound
protein in brain neurons
 cleaved by two secretase enzymes
o Aβ42 – one of the cleavage products In individuals
genetically predisposed to AD
 misfolds & self-associates into amyloid plaques
o All drugs for treatment of AD are aimed at
management of symptoms
o Pursuit of new drugs for AD aimed at:
 Prevent
formation of
Aβ42
peptide
 Remove the
Aβ42
peptide
once it has
formed
 Prevent
interaction
between Aβ
molecules
 Molecular chaperones – “helper proteins” to prevent
nonselective interactions during protein folding to achieve
proper 3D conformation
o Hsp 70 family – bind emerging proteins and prevent
inappropriate interactions
o Chaperonins – allow large new proteins to assemble
without interference from other macromolecules.
 TriC – processes up to 15% of the cells’ proteins
 Proteomics – uses advanced technologies to perform
large-scale studies on diverse proteins
o Proteins are separated using gel electrophoresis
o Proteins are identified using mass spectrometry and
high speed computers
o proteome – entire inventory of organism’s proteins
o Protein microarrays (protein chips) – allow
researchers to screen proteins for various activities
and disorders
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 Protein Engineering – making of artificial genes that code
for proteins of specific amino acids sequences
o Site-directed mutagenesis – allows researchers to
make alterations in single amino acids by altering the
DNA encoding a protein
o Structure-Based Drug Design
 Computer simulations of protein binding sites –
used to design drugs that inhibit specific proteins
 drug Gleevec for treatment of rare cancers
 Computationally designed proteins thattarget
viral proteins
2.6 Formation of Complex Molecular Structure
 Different types of subunits can self-assemble to form
complex structures
o Tobacco Mosaic Virus (TMV) – self-assemble from
ribosomal subunits and proteins
o Cells may use molecular chaperones to assemble
molecular structures

 Protein Adaptation and Evolution Experimental Pathways: Helping Proteins Reach Their Proper
o Adaptations – traits that improve the chance of Folded State
survival of an organism in a specific environment
o Proteins are subject to natural selection  Protein Assembly
o Members of a protein family are thought to have o Some can self-assemble from purified subunits
evolved from a single ancestor gene o Others need molecular chaperones for proper folding
o A particular protein may have different versions  Molecular chaperones – may protect protein
(isoforms) that are tissue- or stage-specific structure during the heat shock response
 heat shock response – involves synthesis of heat
2.5.4 Nucleic Acids shock proteins that prevent denaturation of
existing proteins
 Nucleic acids – polymers of nucleotides that store and
transmit genetic information  Heat shock proteins and other chaperones – prevent
o Deoxyribonucleic acid (DNA) –holds the genetic aggregation of denatured or newly synthesized proteins
information in all cellular organisms and some viruses o Chaperones also move newly synthesized proteins
o Ribonucleic acid (RNA) – genetic material in some across membranes
viruses
 protein GroEL – synthesized in E. coli
 Nucleotides – connected by 3’-5’ phosphodiester bonds o essential for proper folding of other cellular proteins
between the phosphate of o acts in conjunction with another protein, GroES
one nucleotide and the 3’  Attachment of GroES to GroEL induces a
carbon of the next. conformational change in the GroEL protein
o three parts: o GroEL-GroES complex – assists a protein in achieving
 A five-carbon sugar its native state
 A phosphate group
 A nitrogenous base
 either purines or pyrimidines
 purines are adenine and
guanine in both DNA and RNA
 pyrimidines are cytosine and
uracil in RNA; uracil → thymine in
DNA

 RNA: single stranded and DNA: double stranded

o RNA may fold back on
itself to form complex
three dimensional
structures, as in
ribosomes
o RNA may have catalytic
activity; such RNA
enzymes are called
ribozymes.
o Adenosine triphosphate
(ATP) is a nucleotide that
plays a key role in cellular metabolism
o guanosine triphosphate (GTP) serves as a switch to
turn on some proteins

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