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CHAPTER 2
The Chemical Basis of Life
Introduction
• Understanding cellular function requires
knowledge of structure.
• Structure and function in cells is closely
related to the structure of molecules and
atoms.
• The study of chemistry is essential for
understanding cell biology.
2.1 Covalent Bonds (1)
• Bonds between
atoms with shared
pairs of electrons are
called covalent
bonds.
– Molecules are stable
combinations of
atoms held together
by covalent bonds.
– Compounds are
molecules with more
than one type of
atom.
Covalent Bonds (2)
• Atoms tend fill their outer electron shell by
sharing electrons with other atoms.
– Hydrogen forms a single covalent bond by
sharing its unpaired electron.
– Oxygen forms two covalent bonds by sharing
two unpaired electrons.
– Water results when oxygen bonds with two
hydrogens.
Covalent Bonds (3)
• It requires 80-100 kilocalories to break a mole of
covalent bonds.
• Multiple bonds are formed when more than one
pair of electrons are shared by two atoms.
• Shared electrons stay closest to the nucleus with
the highest electronegativity.
– Depends upon the number of protons in nucleus.
– Depends upon the distance of the shard electrons
from the nucleus.
Covalent Bonds (4)
• Polar and Nonpolar Molecules
– Polar molecules have asymmetric
distributions of electrical charge.
– Nonpolar molecules lack polarized bonds.
– Some biological molecules, such as proteins
and phospholipids, have both polar and
nonpolar regions.
Covalent Bonds (5)
• Ionization
– Ions result when strongly electronegative
nuclei capture electrons.
– Anions have extra electrons.
– Cations have lost electrons.
– Free radicals are unstable atoms or
molecules with unpaired electrons.
The Human Perspective: Free Radicals as a
Cause of Aging (1)
• Free radicals are atoms or molecules with
an unpaired electron.
– They are formed during normal metabolism.
– Are highly reactive and damage
macromolecules such as DNA.
– May play a role in aging.
The Human Perspective: Free Radicals as a
Cause of Aging (2)
• Superoxide dismutase (SOD) is an
enzyme that destroys the superoxide
radical (O2.–).
– SOD protects cells from damage due to the
superoxide radical.
– SOD extends the life span of laboratory
animals that overproduce it.
The Human Perspective: Free Radicals as a
Cause of Aging (3)
•
Calorie restriction:
– Extends the lifespan of experimental
animals.
– Results in decreased production of free
radicals.
– A new study indicates that individuals on a
diet containing 25% fewer calories show
reduced levels of DNA damage.
2.2 Noncovalent Bonds (1)
• Noncovalent bonds are attractive forces
that are weaker than covalent bonds.
• Weak bonds are broken and re-formed.
• Weak bonds play an important role in
dynamic cellular processes.
Noncovalent Bonds (2)
• Types of
noncovalent bonds
– 1. Ionic bonds –
attractions between
charged atoms.
• Are weakened in the
presence of water.
• They may be
significant within
large biological
molecules.
Noncovalent ionic bonds
Noncovalent Bonds (3)
2. Hydrogen bonds:
-- A hydrogen bond occurs when
covalently bound hydrogen has a partial
positive charge and attracts electrons of a
second atom.
-- H-bonds determine the structure and
properties of water.
-- H-bonds occur in biological molecules,
such as between the strands of DNA.
Hydrogen bonds
Noncovalent Bonds (4)
3. Hydrophobic interaction and van de
Waals forces:
- These occur when nonpolar molecules
associate and minimize their exposure to
polar molecules.
- van der Waals forces, or attractions
between nonpolar molecules, are due to
transient dipole formation.
Noncovalent Bonds (5)
• The Life-Supporting
Properties of Water
– The structure of water
is suitable for
sustaining life.
• It is asymmetric – both
H atoms are on one
side.
• Both covalent O–H
bonds are highly
polarized.
• All three atoms readily
form H-bonds.
Noncovalent Bonds (6)
• The Life-Supporting Properties of Water
– The properties of water result from its
structure.
•
•
•
•
It is asymmetric—both H atoms are on one side.
It requires a lot heat to evaporate it.
It is an excellent solvent for many substances.
It determines the interactions between many
biological solutes.
The importance of water in protein structure
2.3 Acids, Bases, and Buffers (1)
• Acids release protons.
• Bases accept protons.
• Amphoteric molecules can act as either
acids or bases. For example, water:
H3O ↔ H+ + H2O ↔ OH– + H+
Acid
Amphoteric
molecule
Base
Acids, Bases, and Buffers (2)
• Acidity is measure using the pH scale.
– pH = –log [H+]
– The ion product constant for water is
Kw = [H+][OH–] = 10-14 at 25 °C.
– As [H+] increases, then [OH-] decreases so
that the product equals 10–14.
Acids, Bases, and Buffers (3)
• Biological processes are sensitive to pH.
– Changes in pH affect the ion state and
function of proteins.
– Buffers in living systems resist changes in
pH.
– For example, bicarbonate ions and carbonic
acid buffer the blood:
HCO3– + H+ ↔ H2CO3
Bicarbonate
ion
Hydrogen
ion
Carbonic
acid
2.4 The Nature of Biological
Molecules (1)
• Carbon is central to the chemistry of life.
– Carbon forms four covalent bonds, with itself
or other atoms.
– Carbon-containing molecules produced by
living organisms are called biochemicals.
The Nature of Biological Molecules
(2)
• Carbon is central to
the chemistry of life
– Hydrocarbons:
• Contain only carbon
and hydrogen.
• Vary in the number of
carbons, and the
number of double and
triple bonds between
carbons.
The Nature of Biological Molecules
(3)
• Functional groups—groups of atoms
giving organic molecules different
characteristics and properties.
• Functional classification of biological
molecules:
Macromolecules: large structural and
functional molecules in cells. Include four
major categories: proteins, nucleic acids,
polysaccharides and lipids.
The Nature of Biological Molecules
(4)
•
•
•
Building blocks of macromolecules
include amino acids, nucleotides, sugars,
and fatty acids.
Metabolic intermediates: compounds
formed in metabolic pathways.
Molecules of miscellaneous function:
include vitamins, hormones, ATP, and
metabolic waste products.
Monomers and polymers
2.5 Four Types of Biological
Molecules (1)
Four Types of Biological Molecules
(2)
• Carbohydrates include simple sugars and
sugar polymers.
– They serve as energy storage molecules.
– Structure:
• Chemical formula is (CH2O)n
• Ketose sugars have a carbonyl (C=O) on an
internal carbon
• Aldose sugars have a carbonyl on a terminal
carbon.
• Sugars can be linear but sometimes form ring
structures.
The structures of sugars
Four Types of Biological Molecules
(3)
• Carbohydrates
– Stereoisomerism:
• Asymmetric carbons bond to four different groups.
• Molecules with asymmetric carbons can exist in
two mirror-image configurations called
enantiomers or stereoisomers.
• Enantiomers can be as either D- or L-isomers.
• Sugars can have many asymmetric carbons, but
are designated D- or L- according to the
arrangement around the carbon farthest from the
carbonyl group.
Stereoisomerism
Four Types of Biological Molecules
(4)
• Carbohydrates
– Linking Sugars
Together:
• Glycosidic bonds are
–C—O—C– links
between sugars.
• Disaccharides are used
as a source of readily
available energy.
• Oligosaccharides are
found bound to cells
surface proteins and
lipids, and may be used
for cell recognition.
Four Types of Biological Molecules
(5)
• Carbohydrates
– Polysaccharides are
polymers of sugars
joined by glycosidic
bonds.
• Glycogen is an animal
product made of
branched glucose
polymers.
• Starch is a plant
product made of both
branched and
unbranched glucose
polymers.
Four Types of Biological Molecules
(6)
• Cellulose, chitin, and
glycosaminoglycans
(GAGs): structural
polysaccharides
– Cellulose: plant product
made of unbranched
polymers
– Chitin: component of
invertebrate exoskeleton
made
– GAGs: composed of two
different sugars and found
in extracellular space.
Four Types of Biological Molecules
(7)
• Lipids are a diverse group of nonpolar
molecules.
– Fats are made of glycerol linked by three
ester bonds to three fatty acids (Fas).
• FAs are unbranched hydrocarbons with one
carboxyl group; they are amphipathic.
• Saturated FAs lack C=C double bonds and are
solid at room temperature.
• Unsaturated FAs have one or more C=C double
bonds and are liquid at room temperature.
Fats and fatty acids
Fats and fatty acids
Four Types of Biological
Molecules (8)
• Steroids are four-ringed animal lipids that have
been implicated in atherosclerosis.
• Phospholipids are amphipathic lipids that are a
major component of cell membranes.
Four Types of Biological
Molecules (9)
• Proteins are
polymers of amino
acids and form a
diverse group of
macromolecules.
– They exhibit a high
degree of
specificity.
– They have a variety
of cellular
functions.
Four Types of Biological
Molecules (10)
• The Building Blocks of Proteins
– Amino acids have an α carbon, an amine
group, a carboxyl group, and a variable R
group.
– Amino acids in nature occurs as the L
stereosisomer.
– Amino acids are linked together by peptide
bonds into a polypeptide chain to make a
protein.
Amino acid structure
Four Types of Biological
Molecules (11)
• Peptide bonds form between the αcarbonyl and the α-amino of participating
amino acids.
• Amino acids differ in the R group attached
to one of the bonds of the α-carbon.
– R groups may be polar charged.
– R groups may be polar uncharged.
– R groups may be nonpolar.
The chemical structures of amino acids
The chemical structures of amino acids
Four Types of Biological
Molecules (12)
• R groups may have other properties.
– Glycine has only –H as its R group and is
small.
– The α-carbon of proline is part of a ring,
creating kinks in the protein.
– Cysteine forms disulfide bridges (—SS—)
with other cysteines.
– The nature of the R groups determines the
function of the protein.
Hydrophobic and hydrophilic amino acid
residues in the protein cytochrome c
Four Types of Biological
Molecules (13)
• The Structure of Proteins
– Primary structure, the sequence of amino
acids in the polymer, is critical to the protein
function.
– Secondary structure refers to the
conformation of adjacent amino acids into αhelix, β-sheet, hinges, turns, turns, loops, or
finger-like extensions.
Secondary structure of proteins
Secondary structure of proteins
Four Types of Biological
Molecules (14)
• Tertiary structure is
the conformation of
the entire polymer.
– It is stabilized by
noncovalent bonds.
– It is studied by X-ray
crystallography.
– Proteins can be
fibrous or globular.
Types of noncovalent bonds maintaining the
conformation of proteins
Four Types of Biological
Molecules (15)
• Myoglobin: The First
Globular Proteins Whose
Tertiary Structure Was
Determined
– Stores oxygen in
muscle cells.
– Has a heme prosthetic
group that binds O2.
– Structure derived
using X-ray
crystallography.
Four Types of Biological
Molecules (16)
• Protein Domains
– Domains occur when
proteins are composed
of two or more distinct
regions.
– Each domain is a
functional region
Four Types of Biological
Molecules (17)
• Dynamic Changes
within Proteins
– May occur with protein
activity.
– Conformational
changes are nonrandom movements
triggered by the
binding of a specific
molecule.
Four Types of Biological
Molecules (18)
• Quaternary
structure refers to
proteins composed of
subunits.
– It refers to the manner
in which subunits
interact.
Four Types of Biological
Molecules (19)
• Protein-Protein Interactions
– Different proteins can become physically
associated to form a multiprotein
complex.
Four Types of Biological
Molecules (20)
• Protein-Protein
Interactions
– Can be studied
using the yeast
two-hybrid (Y2H).
– The Y2H is an
indirect assay and
includes lots of
uncertainties.
Four Types of Biological
Molecules (21)
• Protein-Protein
Interactions
– Results from largescale studies can
be presented in the
form of a network.
– A list of potential
interactions can be
elucidate unknown
processes.
Four Types of Biological
Molecules (22)
• Protein Folding is a
process that occurs in
various steps.
– Anfinsen observed
that unfolding is due to
denaturation, brought
about by various
agents.
– Removal of denaturing
agents could lead to
refolding.
Four Types of Biological
Molecules (23)
• 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.
Two alternate pathways for protein folding
Four Types of Biological
Molecules (24)
• The Role of Molecular Chaperones
– Molecular chaperones are “helper proteins”
to prevent nonselective interactions during
protein folding.
• Hsp 70 family bind emerging proteins and prevent
inappropriate interactions.
• Chaperonins allow large new proteins to assemble
without interference from other macromolecules.
The role of molecular chaperones in
encouraging protein folding
The Human Perspective: Protein Misfolding
Can Have Deadly Consequences (1)
• Creutzfeld-Jakob Disease (CJD) results
from misfolded protein in the brain.
– Healthy brains contain a normal protein, PrPc.
– CJD brains have PrPSc, which is identical or
similar to PrPc but is misfolded.
– “Mad cow disease”, kuru, and sccrapie are
also caused by PrPSc.
A contrast in structure
The Human Perspective: Protein Misfolding
Can Have Deadly Consequences (2)
• Alzheimer’s disease (AD) involves misfolded
proteins that accumulate in the brains of affected
individuals.
– A membrane-bound protein in brain neurons, called
amyloid precursor protein (APP), is cleaved by two
secretase enzymes.
– In individuals genetically predisposed to AD one of
the cleavage products is Aβ42, a protein that misfolds
and self-associates into amyloid plaques.
Alzheimer’s disease
The Human Perspective: Protein Misfolding
Can Have Deadly Consequences (3)
• All drugs for treatment of AD are aimed at
management of symptoms.
• 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.
Formation of the Aβ peptide
Four Types of Biological
Molecules (25)
• The Emerging Field of Proteomics
– The proteome is the entire inventory of an
organism’s proteins.
– Proteomics uses advanced technologies to
perform large-scale studies on diverse
proteins.
• Proteins are separated using gel electrophoresis.
• Proteins are identified using mass spectrometry
and high speed computers.
The study of proteomics often requires the
separation of complex mixtures of proteins
Identifying proteins by mass spectrometry
Four Types of Biological
Molecules (26)
• The Emerging Field of Proteomics
– Protein microarrays (protein chips) allow
researchers to screen proteins for various
activities and disorders.
– In a near future biotechnology companies will
be manufacturing microarrays containing
antibodies for different blood proteins, which
may indicate that a person may be suffering
from a particular disease.
Global analysis of protein activities using
protein chips
Four Types of Biological
Molecules (27)
• Protein Engineering
– Current technology allows the making of artificial
genes that code for proteins of specific amino acids
sequences.
– Knowledge of a protein’s amino acid sequence rarely
allows prediction of a protein’s structure.
– Site-directed mutagenesis allows researchers to
make alterations in single amino acids by altering the
DNA encoding a protein.
Four Types of Biological
Molecules (28)
• Structure-Based Drug Design
– Computer simulations of protein binding sites
are used to design drugs that inhibit specific
proteins.
– An example of such application is the drug
Gleevec for treatment of rare cancers.
Development of a protein-targeting drug
Four Types of Biological
Molecules (29)
• Protein Adaptation and Evolution
– Adaptations are traits that improve the chance
of survival of an organism in a specific
environment.
– Proteins are subject to natural selection.
– Members of a protein family are thought to
have evolved from a single ancestor gene.
– A particular protein may have different
versions (isoforms) that are tissue- or stagespecific.
Distribution of polar, charged amino acid
residues in the enzyme malate
dehydrogenase
Four Types of Biological
Molecules (30)
• Nucleic acids are polymers of nucleotides that
store and transmit genetic information.
– Deoxyribonucleic acid (DNA) holds the genetic
information in all cellular organisms and some
viruses.
– Ribonucleic acid (RNA) is the genetic material in
some viruses.
– Nucleotides are connected by 3’-5’ phosphodiester
bonds between the phosphate of one nucleotide and
the 3’ carbon of the next.
Nucleotides and nucleotide strands of RNA
Four Types of Biological
Molecules (31)
• Each nucleotide consists of three parts:
– A five-carbon sugar
– A phosphate group
– A nitrogenous base
• Bases are either purines or pyrimidines.
• The purines are adenine and guanine in both
DNA and RNA.
• The pyrimidines are cytosine and uracil in RNA;
uracil is replaced by thymine in DNA.
Nitrogenous bases in nucleic acids
Four Types of Biological
Molecules (32)
• RNA is usually single stranded and DNA is
usually double stranded.
– RNA may fold back on itself to form complex three
dimensional structures, as in ribosomes.
– RNA may have catalytic activity; such RNA enzymes
are called ribozymes.
– Adenosine triphosphate (ATP) is a nucleotide that
plays a key role in cellular metabolism, whereas
guanosine triphosphate (GTP) serves as a switch to
turn on some proteins.
RNA and the ribosome
RNA and the ribosome
2.6 The Formation of Complex
Molecular Structure
• Different types of subunits can selfassemble to form complex structures.
• One example is the tobacco mosaic virus
(TMV), which was shown to self-assemble
from ribosomal subunits and proteins.
• Cells may use molecular chaperones to
assemble molecular structures.
Experimental Pathways: Helping Proteins
Reach Their Proper Folded State (1)
• Some proteins can self-assemble from
purified subunits.
• Other proteins require molecular
chaperones for proper folding.
– Molecular chaperones may protect protein
structure during the heat shock response.
– The heat shock response involves synthesis
of heat shock proteins that prevent
denaturation of existing proteins.
Experimental Pathways: Helping Proteins
Reach Their Proper Folded State (2)
• Heat shock proteins and other chaperones
prevent aggregation of denatured or newly
synthesized proteins.
• Chaperones also move newly synthesized
proteins across membranes.
• The protein GroEL is synthesized in E. coli
is essential for the proper folding of other
cellular proteins.
GroEL
Experimental Pathways: Helping Proteins
Reach Their Proper Folded State (3)
• GroEl acts in conjunction
with another protein,
GroES.
• Attachment of GroES to
GroEL induces a
conformational change in
the GroEL protein.
• The GroEL-GroES
complex assists a protein
and achieving its native
state.
GroEL-GroES-assisted folding of a
polypeptide