2
Molecules and Membranes
2 Molecules and Membranes
•
The Molecules of Cells
•
Enzymes as Biological Catalysts
•
Cell Membranes
Introduction
Cells are incredibly complex and
diverse.
Cells obey the same laws of chemistry
and physics that determine the
behavior of nonliving systems.
Modern cell biology seeks to understand
cellular processes in terms of chemical
and physical reactions.
The Molecules of Cells
Water is the most abundant molecule in
cells.
It is polar; the hydrogen atoms have a
slight positive charge and the oxygen
has a slight negative charge.
Water molecules can form hydrogen
bonds with each other or with other
polar molecules, and interact with ions.
Figure 2.1 Characteristics of water (Part 1)
Figure 2.1 Characteristics of water (Part 2)
Figure 2.1 Characteristics of water (Part 3)
The Molecules of Cells
Ions and polar molecules are readily
soluble in water (hydrophilic).
Nonpolar molecules cannot interact with
water and are poorly soluble
(hydrophobic).
The Molecules of Cells
Inorganic ions constitute 1% or less of
the cell mass and include:
• Sodium (Na+)
• Potassium (K+)
• Magnesium (Mg2+)
• Calcium (Ca2+)
• Phosphate (HPO42−)
• Chloride (Cl−)
• Bicarbonate (HCO3−)
The Molecules of Cells
The organic molecules are the unique
constituents of cells.
Most belong to one of four classes of
molecules:
• Carbohydrates
• Lipids
• Proteins
• Nucleic acids
The Molecules of Cells
Carbohydrates include simple sugars
and polysaccharides.
Monosaccharides (simple sugars) are
the major nutrients of cells. The basic
formula is (CH2O)n.
Glucose (C6H12O6) provides the principal
source of cellular energy.
Figure 2.2 Structure of simple sugars (Part 1)
Figure 2.2 Structure of simple sugars (Part 2)
Figure 2.2 Structure of simple sugars (Part 3)
The Molecules of Cells
Monosaccharides are joined together by
dehydration reactions (H2O is removed)
resulting in glycosidic bonds.
Oligosaccharides are polymers of a
few sugars.
Polysaccharides are macromolecules;
polymers of hundreds or thousands of
sugars.
Figure 2.3 Formation of a glycosidic bond
The Molecules of Cells
Common polysaccharides:
• Glycogen: stores glucose in animal
cells.
• Starch: stores glucose in plant cells.
Both are composed entirely of glucose
molecules in the α configuration.
Figure 2.4 Structure of polysaccharides (Part 1)
The Molecules of Cells
Cellulose is the main structural
component of plant cell walls.
It is composed entirely of glucose
molecules in the β configuration.
The β(1→4) linkages cause cellulose to
form long extended chains that pack
side by side to form fibers of great
mechanical strength.
Figure 2.4 Structure of polysaccharides (Part 2)
The Molecules of Cells
Chitin is the animal parallel of cellulose;
it forms the exoskeletons of crabs and
insects.
Oligosaccharides and polysaccharides
also play roles in protein folding and act
as markers involved in cell recognition
and interactions.
The Molecules of Cells
Lipids have three main roles:
• Energy storage
•
Major component of cell membranes
•
Important in cell signaling as steroid
hormones and messenger molecules
The Molecules of Cells
Fatty acids are long hydrocarbon chains
(16 or 18 carbons) with a carboxyl
group (COO–) at one end.
Unsaturated fatty acids have one or
more double bonds. Saturated fatty
acids have no double bonds.
The hydrocarbon chain is hydrophobic.
Figure 2.5 Structure of fatty acids
The Molecules of Cells
Fatty acids are stored as
triacylglycerols, (triglycerides, or
fats): three fatty acids linked to a
glycerol molecule.
They are insoluble in water and
accumulate as fat droplets in the
cytoplasm.
They can be broken down for use in
energy-yielding reactions.
Figure 2.6 Structure of triacylglycerols (Part 1)
Figure 2.6 Structure of triacylglycerols (Part 2)
The Molecules of Cells
Fats are more efficient energy storage
than carbohydrates, yielding more than
twice as much energy per weight of
material broken down.
This is important for animals because of
their mobility.
The Molecules of Cells
Phospholipids: principal components of
cell membranes.
Two fatty acids are joined to a polar
head group.
Glycerol phospholipids: the fatty acids
are bound to glycerol, which is bound
to a phosphate group, and often
another polar group.
Figure 2.7 Structure of phospholipids (Part 1)
Figure 2.7 Structure of phospholipids (Part 2)
Figure 2.7 Structure of phospholipids (Part 3)
Figure 2.7 Structure of phospholipids (Part 4)
Figure 2.7 Structure of phospholipids (Part 5)
Figure 2.7 Structure of phospholipids (Part 6)
The Molecules of Cells
Sphingomyelin is the only nonglycerol
phospholipid in cell membranes.
The polar head group is formed from
serine instead of glycerol.
The Molecules of Cells
All phospholipids have hydrophobic tails
and hydrophilic head groups.
• They are amphipathic molecules:
part water-soluble and part waterinsoluble.
This is the basis for the formation of
biological membranes.
The Molecules of Cells
Many cell membranes also have:
Glycolipids: two hydrocarbon chains
and a carbohydrate polar head group
(amphipathic).
Cholesterol: four hydrophobic
hydrocarbon rings and a polar hydroxyl
(OH) group (amphipathic).
Figure 2.8 Structure of glycolipids
Figure 2.9 Cholesterol and steroid hormones (Part 1)
Figure 2.9 Cholesterol and steroid hormones (Part 1)
The Molecules of Cells
The steroid hormones (e.g., estrogens
and testosterone) are derivatives of
cholesterol; they act as chemical
messengers.
Derivatives of phospholipids also serve
as messenger molecules within cells.
The Molecules of Cells
Nucleic acids: principal informational
molecules of the cell.
• Deoxyribonucleic acid (DNA) is the
genetic material.
• Ribonucleic acid (RNA)—several
types
The Molecules of Cells
Messenger RNA (mRNA) carries
information from DNA to the ribosomes.
Ribosomal RNA and transfer RNA are
involved in protein synthesis.
Other RNAs are involved in regulation of
gene expression, and processing and
transport of RNAs and proteins.
The Molecules of Cells
DNA and RNA are polymers of
nucleotides, which consist of purine
and pyrimidine bases linked to
phosphorylated sugars.
DNA has two purines (adenine and
guanine) and two pyrimidines
(cytosine and thymine).
RNA has uracil in place of thymine.
Figure 2.10 Components of nucleic acids (Part 1)
Figure 2.10 Components of nucleic acids (Part 2)
The Molecules of Cells
The bases are linked to sugars to form
nucleosides.
DNA has the sugar 2′-deoxyribose,
RNA has ribose.
Nucleotides have one or more
phosphate groups linked to the 5′
carbon of the sugars.
Figure 2.10 Components of nucleic acids (Part 3)
Figure 2.10 Components of nucleic acids (Part 4)
The Molecules of Cells
Polymerization of nucleotides:
Phosphodiester bonds form between
the 5′ phosphate of one nucleotide and
the 3′ hydroxyl of another.
Figure 2.11 Polymerization of nucleotides
The Molecules of Cells
Oligonucleotides are polymers of a few
nucleotides.
RNA and DNA are polynucleotides and
may contain thousands or millions of
nucleotides.
The Molecules of Cells
A polynucleotide chain has a sense of
direction:
One end terminates in a 5′ phosphate
group and the other in a 3′ hydroxyl
group.
Polynucleotides are always synthesized
in the 5′ to 3′ direction.
The Molecules of Cells
Information in DNA and RNA is
conveyed by the order of the bases.
DNA is made up of two polynucleotide
chains. The bases are on the inside,
joined by hydrogen bonds between
complementary base pairs:
•
Guanine with cytosine
•
Adenine with thymine
Figure 2.12 Complementary pairing between nucleic acid bases
The Molecules of Cells
Complementary base pairing allows one
strand of DNA (or RNA) to act as a
template for synthesis of a
complementary strand.
Nucleic acids are thus capable of selfreplication.
The information carried by DNA and RNA
directs synthesis of specific proteins,
which control most cellular activities.
The Molecules of Cells
Other important nucleotides include
adenosine 5′-triphosphate (ATP), the
principal form of chemical energy within
cells.
Some nucleotides (e.g., cyclic AMP) act
as signaling molecules within cells.
The Molecules of Cells
Proteins are the most diverse of all
macromolecules.
Each cell contains several thousand
different proteins.
Proteins direct virtually all activities of
the cell.
The Molecules of Cells
Functions of proteins include:
•
Structural components
•
Transport and storage of small
molecules (e.g., O2)
•
Transmit information between cells
(protein hormones)
•
Defense against infection (antibodies)
•
Enzymes
The Molecules of Cells
Proteins are polymers of 20 different
amino acids.
Each amino acid consists of an α carbon
bonded to a carboxyl group (COO−),
an amino group (NH3+), a hydrogen,
and a distinctive side chain.
Figure 2.13 Structure of amino acids
The Molecules of Cells
Amino acids are grouped based on
characteristics of the side chains:
• Nonpolar side chains
• Polar side chains
• Side chains with charged basic
groups
• Acidic side chains terminating in
carboxyl groups
Figure 2.14 The amino acids (Part 1)
Figure 2.14 The amino acids (Part 2)
Figure 2.14 The amino acids (Part 3)
Figure 2.14 The amino acids (Part 4)
The Molecules of Cells
Amino acids are joined by peptide
bonds.
Polypeptides are chains of amino
acids, hundreds or thousands of amino
acids in length.
One end terminates in an α amino group
(N terminus) and the other in an α
carboxyl group (C terminus).
Figure 2.15 Formation of a peptide bond
The Molecules of Cells
The amino acid sequence is the defining
characteristic of proteins.
The sequence for insulin was worked out
in 1953 by Frederick Sanger. Protein
sequences are now deduced from
sequences of mRNAs.
The unique sequences of amino acids
are determined by the order of
nucleotides in a gene.
Figure 2.16 Amino acid sequence of insulin
The Molecules of Cells
Proteins also have distinct 3-D
conformations that are critical to their
function.
This results from interactions between the
amino acids, so the shape and function of
proteins are determined by their amino
acid sequences.
The Molecules of Cells
Christian Anfinsen demonstrated the
importance of the 3-D structure.
He disrupted proteins by treatments such
as heating, which breaks noncovalent
bonds (denaturation).
If the treatment was mild, the proteins
would return to their normal shape.
Figure 2.17 Protein denaturation and refolding
The Molecules of Cells
Therefore, all the information required to
specify the correct 3-D conformation of
a protein is contained in its primary
amino acid sequence.
Key Experiment, Ch. 2, p. 58 (2)
The Molecules of Cells
Protein structure is frequently analyzed by
X-ray crystallography.
X-rays are directed at the protein; the pattern of X-rays that pass
through is detected on X-ray film.
The X-rays are scattered in
characteristic patterns determined by
the arrangement of atoms in the
molecule.
The Molecules of Cells
John Kendrew was the first to determine
the 3-D structure of a protein,
myoglobin (153 amino acids).
Analysis of 3-D structures has revealed
some basic principles of protein folding,
but the complexity is so great that this
remains an active area of research.
Figure 2.18 Three-dimensional structure of myoglobin
The Molecules of Cells
Protein structure has four levels:
Primary structure: the sequence of
amino acids in the polypeptide chain.
Secondary structure: regular
arrangement of amino acids within
localized regions.
The Molecules of Cells
Two common types of secondary
structure:
α helix and β sheet.
Both are held together by hydrogen
bonds between the CO and NH groups
of peptide bonds.
Figure 2.19 Secondary structure of proteins (Part 1)
Figure 2.19 Secondary structure of proteins (Part 2)
The Molecules of Cells
Tertiary structure: the polypeptide
chain folds due to interactions between
side chains of amino acids in different
regions of the chain.
In most proteins this results in domains,
the basic units of tertiary structure.
Figure 2.20 Tertiary structure (Part 1)
Figure 2.20 Tertiary structure (Part 2)
The Molecules of Cells
A critical determinant of tertiary
structure:
Placement of hydrophobic amino acids
in the interior of the protein and
hydrophilic amino acids on the surface,
where they interact with water.
The Molecules of Cells
Loop regions connect the elements of
secondary structure.
They are on the surface of folded
proteins, where polar components of
the peptide bonds form hydrogen
bonds with water or with the polar side
chains of hydrophilic amino acids.
The Molecules of Cells
Quaternary structure: interactions
between different polypeptide chains in
proteins composed of more than one
polypeptide.
Hemoglobin is composed of four
polypeptide chains.
Figure 2.21 Quaternary structure of hemoglobin
Enzymes as Biological Catalysts
A fundamental role of proteins is to act
as enzymes.
Enzymes are catalysts that increase the
rate of all chemical reactions in cells.
Without enzymes, most biochemical
reactions are so slow that they would
not occur.
Enzymes as Biological Catalysts
Fundamental properties of enzymes:
• Increase rate of chemical reactions
without themselves being consumed or
permanently altered.
• Increase reaction rates without altering
the chemical equilibrium between
reactants and products.
Enzymes as Biological Catalysts
When a substrate (S) is converted to a
product (P), the chemical equilibrium
between S and P is determined by the
laws of thermodynamics.
S P
If an enzyme is present, the conversion
is faster, but equilibrium is unchanged.
S  P
E
Enzymes as Biological Catalysts
Equilibrium is determined by the final
energy states of S and P.
The substrate must first be converted to
a higher energy state, the transition
state.
Energy required to reach the transition
state = activation energy. Enzymes
reduce the activation energy.
Figure 2.22 Catalyzed and uncatalyzed reactions
Enzymes as Biological Catalysts
Enzymes must bind their substrates to
form an enzyme-substrate complex (ES).
The substrate binds to a specific region,
the active site.
The substrate is converted to product while
bound to the active site, then released.
S  E  ES  E  P
Enzymes as Biological Catalysts
Substrate binding to the active site is a
very specific interaction.
Active sites are clefts or grooves on the
surface of an enzyme formed by the
tertiary structure.
Substrates initially bind by hydrogen
bonds, ionic bonds, and hydrophobic
interactions.
Enzymes as Biological Catalysts
Most biochemical reactions involve two
or more different substrates.
Example: a peptide bond joins 2 amino
acids; both are bound to the active site.
The enzyme brings the substrates
together in proper orientation to favor
the transition state.
Figure 2.23 Enzymatic catalysis of a reaction between two substrates
Enzymes as Biological Catalysts
Enzymes also accelerate reactions by
altering the conformation of substrates.
In the lock-and-key model, the
substrate fits precisely into the active
site.
Induced fit: conformation of both
enzyme and substrate is modified.
Figure 2.24 Models of enzyme-substrate interaction (Part 1)
Figure 2.24 Models of enzyme-substrate interaction (Part 2)
Enzymes as Biological Catalysts
Many enzymes participate directly in the
catalytic process.
Specific side chains in the active site
may react with the substrate and form
bonds with reaction intermediates.
Example: chymotrypsin
Enzymes as Biological Catalysts
Chymotrypsin digests proteins by
catalyzing the hydrolysis of peptide
bonds.
Protein  H 2O  Peptide1  Peptide2
Enzymes as Biological Catalysts
Chymotrypsin is a serine protease: these
enzymes cleave peptide bonds
adjacent to specific types of amino
acids.
Chymotrypsin digests bonds adjacent to
hydrophobic amino acids, trypsin
digests bonds next to basic amino
acids.
Enzymes as Biological Catalysts
The active sites of serine proteases
contain serine, histidine, and aspartate.
Substrates bind by insertion of the amino
acid adjacent to the cleavage site into a
pocket at the active site.
The nature of the pocket determines the
substrate specificity of the different
serine proteases.
Figure 2.25 Substrate binding by serine proteases (Part 1)
Figure 2.25 Substrate binding by serine proteases (Part 2)
Figure 2.26 Catalytic mechanism of chymotrypsin (Part 1)
Figure 2.26 Catalytic mechanism of chymotrypsin (Part 2)
Enzymes as Biological Catalysts
This example illustrates several features
of enzymatic catalysis:
• Specificity of enzyme-substrate
interactions.
• Positioning of substrate molecules in
the active site.
• Involvement of active-site residues in
formation and stabilization of the
transition state.
Enzymes as Biological Catalysts
Active sites may bind other small
molecules that participate in catalysis:
• Prosthetic groups: small molecules
bound to proteins that have critical
functional roles.
Example: in myoglobin and
hemoglobin, the prosthetic group is
heme, which carries O2.
Enzymes as Biological Catalysts
•
Metal ions (e.g., zinc or iron) can be
bound to enzymes and play a role in
the catalysis.
• Coenzymes: small organic
molecules that work together with
enzymes to enhance reaction rates.
• Coenzymes are not altered by the
reaction.
Enzymes as Biological Catalysts
Nicotinamide adenine dinucleotide
(NAD+) is a coenzyme that carries
electrons in oxidation–reduction
reactions.
NAD+ can accept H+ and two electrons
from one substrate, forming NADH.
NADH can then donate the electrons to
a second substrate, re-forming NAD+.
Figure 2.27 Role of NAD+ in oxidation–reduction reactions (Part 1)
Figure 2.27 Role of NAD+ in oxidation–reduction reactions (Part 2)
Enzymes as Biological Catalysts
Other coenzymes are involved in the
transfer of a variety of chemical groups.
Many coenzymes are closely related to
vitamins, which contribute part or all of
the structure of the coenzyme.
Table 2.1 Examples of Coenzymes and Vitamins
Enzymes as Biological Catalysts
Enzyme activity can be regulated to
meet various physiological needs that
may arise during the life of the cell.
In feedback inhibition, the product of a
metabolic pathway inhibits an enzyme
involved in its synthesis.
Figure 2.28 Feedback inhibition
Enzymes as Biological Catalysts
Feedback inhibition is a type of
allosteric regulation: enzyme activity
is controlled by the binding of small
molecules to regulatory sites on the
enzyme.
This changes the conformation of the
enzyme and alters the active site.
Figure 2.29 Allosteric regulation
Enzymes as Biological Catalysts
Phosphorylation is a common
mechanism of enzyme regulation.
Phosphate groups are added to the sidechain OH groups of serine, threonine,
or tyrosine.
It can either stimulate or inhibit the
activities of many enzymes.
Figure 2.30 Protein phosphorylation (Part 1)
Figure 2.30 Protein phosphorylation (Part 2)
Cell Membranes
All cell membranes are phospholipid
bilayers with associated proteins.
This common structural organization
underlies a variety of biological
processes and specialized membrane
functions.
Cell Membranes
Phospholipids spontaneously form
bilayers in aqueous solutions.
Such phospholipid bilayers form a
stable barrier between two aqueous
compartments.
They are the basic structure of all
biological membranes.
Figure 2.31 A phospholipid bilayer
Cell Membranes
Cell membrane lipid content and types of
phospholipids vary.
Mammalian plasma membranes have
five major phospholipids.
Plasma membranes of animal cells also
contain glycolipids and cholesterol.
Cell Membranes
Lipid bilayers are 2-dimensional fluids in
which molecules are free to rotate and
move laterally.
Membrane fluidity is determined by
temperature and lipid composition.
Unsaturated fatty acids chains have
double bonds that result in kinks. This
reduces packing and increases
membrane fluidity.
Figure 2.32 Mobility of phospholipids in a membrane
Cell Membranes
Because of its ring structure, cholesterol
helps determine membrane fluidity.
Interactions between the hydrocarbon
rings and fatty acid tails makes the
membrane more rigid.
Cholesterol also reduces interaction
between fatty acids, maintaining
membrane fluidity at lower
temperatures.
Figure 2.33 Insertion of cholesterol in a membrane
Cell Membranes
The fluid mosaic model of membrane
structure was proposed by Singer and
Nicolson in 1972:
Integral membrane proteins inserted into
a phospholipid bilayer, with nonpolar
regions in the lipid bilayer and polar
regions exposed to the aqueous
environment.
Key Experiment, Ch. 2, p. 73 (3)
Cell Membranes
Integral membrane proteins are
embedded directly in the lipid bilayer.
Peripheral membrane proteins are
associated with the membrane
indirectly, generally by interactions with
integral membrane proteins.
Figure 2.34 Fluid mosaic model of membrane structure
Cell Membranes
Transmembrane proteins span the
lipid bilayer, with portions exposed on
both sides.
Membrane-spanning portions are usually
α-helical regions of 20 to 25 nonpolar
amino acids.
Cell Membranes
Some membrane-spanning proteins
have a β-barrel, formed by folding of β
sheets into a barrel-like structure.
(In some bacteria, chloroplasts, and
mitochondria).
Figure 2.35 Structure of a b barrel
Cell Membranes
The selective permeability of
membranes allows a cell to control its
internal composition.
Small, nonpolar molecules can diffuse
across the lipid bilayer: CO2, O2, H2O.
Ions and larger uncharged molecules,
such as glucose, cannot diffuse across.
Figure 2.36 Permeability of phospholipid bilayers
Cell Membranes
Some transmembrane proteins act as
transporters.
Channel proteins form open pores
across the membrane. They can be
selectively opened and closed in
response to extracellular signals.
Ion channels allow the passage of
inorganic ions.
Figure 2.37 Channel and carrier proteins (Part 1)
Cell Membranes
Carrier proteins selectively bind and
transport small molecules, such as
glucose.
Carrier proteins bind specific molecules
and then undergo conformational
changes that open channels through
which the molecule can pass.
Figure 2.37 Channel and carrier proteins (Part 2)
Cell Membranes
Passive transport: molecule movement
across the membrane is determined by
concentration and electrochemical
gradients.
Active transport: molecules can be
transported against a concentration
gradient if coupled to ATP hydrolysis as
a source of energy.
Figure 2.38 Model of active transport