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Chapter 5:
The Structure and Function
of Large Biological Molecules
AP Biology
Overview: The Molecules of Life
•
•
Though there is an enormous diversity of molecules on Earth, the critically important
large molecules of all living things fall into just 4 main classes:
–
1) Carbohydrates
–
2) Lipids
–
3) Proteins
–
4) Nucleic Acids
Within cells, small organic molecules are joined together to form larger molecules
–
Members of these classes consist of 1000s of atoms and are thus called
macromolecules
•
The architecture of these large biological molecules helps explain how they
work
–
–
They exhibit unique emergent properties arising from the orderly arrangement
of their atoms
This chapter considers how macromolecules are built, as well as examining the
structure and function of all 4 classes of large biological molecules
Concept 5.1:
Macromolecules are polymers, built
from monomers
• The macromolecules in carbohydrates, proteins, and nucleic acids
are chain-like molecules called polymers
–
Polys-many
–
Meris-part
• POLYMER: long molecule consisting of many similar or
identical building blocks linked by covalent bonds (like a train
made up of many cars)
–
The repeating units that are the building blocks of a polymer are
smaller molecules called MONOMERS
The Synthesis of Polymers
•
Though the classes of polymers have different monomers, the chemical mechanisms
by which cells make and break down polymers are basically the same:
–
Monomers are connected by covalently bonding to each other through loss of a
water molecules
•
This type of reaction is called a CONDENSATION REACTION, or more
specifically, a DEHYDRATION REACTION (because a molecule of water
is lost)
– One of the monomers provides a hydroxyl group (-OH) and the other
provides a hydrogen (-H) to make up for the water molecule that is lost
•
–
This reaction continues to
repeat, adding monomers to
the chain one by one,
forming a polymer
Dehydration is sped up by enzymes
(specialized macromolecules that
speed up chemical reactions in cells)
The Breakdown of Polymers
•
Polymers are broken down by HYDROLYSIS (reverse of dehydration; hydro = water,
lysis = break)
–
–
Bonds between monomers are broken by
the addition of water molecules
•
The hydrogen atom from water
attaches to one monomer
•
The hydroxyl group (-OH) from water
attaches to adjacent monomer
Example of hydrolysis: digestion
•
Most of the organic material in food is in the form of polymers that must be
broken down because they are too large to enter our cells
•
Released monomers are the absorbed into bloodstream for distribution to
all body cells
–
Here, they can be reassembled (using dehydration reactions) into
new, different polymers that can perform specific function required by
those cells
Animation: Polymers
The Diversity of Polymers
•
Each cell has 1000s of different kinds of macromolecules
–
The types of macromolecules found in cells differ from cell to cell in the same
organism (depending on that cell’s functions and needs)
2
•
3
H
HO
Even more variety in types of macromolecules within cells is observed when
considering 2 different organisms of the same species
–
•
–
Ex) Different DNA/proteins in humans lead to different characteristics
Even greater variation is found between 2 different species
Though all these different polymers are constructed from only 40-50 common
monomers (as well as some others that rarely occur), a huge variety of polymers exist
due to different arrangements of their monomers
•
–
Like the alphabet: 26 letters can construct 100s of 1000s of words
Despite this immense diversity of macromolecules, we can still group them roughly by
class based on molecular structure and function
Concept Check 5.1
• 1) What are the 4 main classes of large biological molecules?
• 2) How many molecules of water are needed to completely
hydrolyze a polymer that is 10 monomers long?
• 3) Suppose you eat a serving of green beans. What reactions
must occur for the amino acid monomers in the protein of the
beans to be converted to proteins in your body?
Concept 5.2:
Carbohydrates serve as fuel and
building material
• Carbohydrates include both sugars and polymers of sugars
– The simplest carbohydrates are called monosaccharides
(or simple sugars)
• 2 monosaccharides can be joined to form double
sugars, or disaccharides
– Carbohydrates also include polysaccharides, polymers
composed of many sugar building blocks
Sugars
• Monosaccharides : monos = single; saccar = sugar
–
Generally have molecular formulas that are some multiple of the unit
CH2O
• The most common monosaccharide is glucose (C6H12O6)
–
Though it is convenient to draw glucose and other sugars with a linear
carbon skeleton, this representation is not completely accurate
• In aqueous solutions, most sugars form rings
Functions of Monosaccharides
• MONOSACCHARIDE FUNCTIONS:
–
1) Monosaccharides are major nutrients for cells
• Ex) During cellular respiration, cells extract energy from glucose
–
2) Carbon skeletons of sugars can also serve as raw material for
synthesis of other types of small organic molecules (amino acids, fatty
acids)
–
3) Sugar molecules not immediately used in these ways are usually
converted into disaccharides and polysaccharides
•
Monosaccharides can be classified according to certain features:
–
Carbonyl group
•
Called aldoses (or aldehyde sugars)
if carbonyl group is at end of carbon
skeleton
–
•
Called ketoses (or ketone sugars) is
carbonyl group is located within the
carbon skeleton
–
–
Ex) Fructose – a structural
isomer of glucose
Size of carbon skeleton
•
–
Ex) Glucose
Can range from 3-7 carbons long (hexoses, pentoses, trioses are most common)
Spatial arrangement of their parts around asymmetric carbons (carbon attached to 4
different atoms)
•
A disaccharide is formed when a dehydration reaction joins two monosaccharides
–
•
This covalent bond is called a glycosidic linkage
Examples of disaccharide synthesis
–
a)Dehydration reaction in the synthesis of maltose
•
Maltose is formed by linking 2 glucose monomers
– Also known as malt sugar, used in brewing beer
•
The glycosidic linkage joins carbon 1 of one glucose to carbon 4 of the 2nd glucose
–
If we joined the monomers in a different way, it would result in a different
disaccharide
•
Examples of disaccharide synthesis (continued)
–
b)Dehydration reaction in synthesis of sucrose
• Sucrose is considered table sugar
– It is composed of glucose and fructose monomers
• Plants usually transport carbohydrates from leaves to roots and to other
nonphotosynthetic organelles in this form
–
Notice that fructose, though a hexose like glucose, forms a 5-sided ring
Animation: Disaccharides
Polysaccharides
• Polysaccharides are macromolecules – polymers with a few 100-1000
monosaccharides joined by glycosidic linkages
– Some polysaccharides are used for storage and then hydrolyzed
as needed to provide sugar for the cell
• Other polysaccharides serve as building material for
structures that protect cell or whole organism
– The structure and function of polysaccharides are determined by
their monomers as well as by positions of their glycosidic
linkages
Storage Polysaccharides
•
Both plants and animals store sugars for later use in the form of storage polysaccharides
–
PLANTS: store starch, a polymer of glucose molecules, as granules in plastids,
including chloroplasts
•
–
Starch allows plant to stockpile surplus glucose that can later by broken down into
its individual monomers by hydrolysis to obtain energy
ANIMALS: most animals also have enzymes that can hydrolyze plant starch to make
glucose available as a nutrient for cells
•
Potatoes and grain (fruit of wheat, corn, rice, and other grasses) are the main
sources of starch in the human diet
•
Animals store a polysaccharide called glycogen
–
Hydrolysis of glycogen in liver and muscle cells releases glucose when
demand for sugar increases
–
This stored fuel cannot sustain an animal for long (glycogen stores deplete in
~1 day in humans unless replenished by food consumption)
•
Storage polysaccharides of plants and animals
–
a) Most of the glucose monomers in starch
are joined by 1-4 linkages (carbon 1 and
carbon 4)
– The angle of these bonds makes
the polymer helical
•
The simplest form of starch,
AMYLOSE, is unbranched
–
•
–
Amylopectin, a more complex starch, is a branched polymer with 1-6
linkages at the branch points
The light ovals in the micrograph are granules of starch within a chloroplast of a
plant cell
b) Glycogen – an animal polysaccharide
•
Glycogen is more branched than amylopectin
•
Animals stockpile glycogen as dense clusters of granules within liver and muscle
cells (micrograph shows part of a liver cell)
•
Mitochondria are organelles that help break down sugars – site of cell respiration
Structural Polysaccharides
•
Organisms use structural polysaccharides to build strong materials
–
Ex) Cellulose is a polysaccharide that is the major component of cells walls in plants
–
•
Like starch, cellulose is a polymer made up of glucose monomers
The glycosidic linkages between theses 2 polymers are different, however,
because there are actually 2 slightly different ring structures for glucose
–
When glucose forms a ring, the hydroxyl group attached to carbon 1 can be
positioned either above or below the plane of the ring,
–
This results in an alpha ( ) (below) and beta ( ) (above) ring form for
glucose
Animation: Polysaccharides
•
These different glycosidic linkages in starch and cellulose give these 2 molecules different 3D shapes
–
•
Polymers with
glucose are helical (starch)
•
Polymers with
glucose are straight (cellulose)
This leaves some of the hydroxyl groups on the glucose monomers free to H-bond with
hydrogen atoms of other
cellulose molecules that lay
parallel to it
•
Parallel cellulose molecules
held together in this way
are grouped into units
called microfibrils, which
form a strong building
material for plants
•
Enzymes that digest starch by hydrolyzing alpha linkages are not able to hydrolyze beta
linkages in cellulose because of the different shapes of the 2 molecules
–
–
Because humans do not posses enzymes to digest cellulose, any cellulose in our food
passes through the digestive tract and is eliminated with our feces
•
Along the way, cellulose abrades the wall of the digestive tract, stimulating the
lining to secrete mucus (which aids in smooth passage of food through tract)
•
Cellulose is thus an important part of a healthy diet in the form of fiber
Some prokaryotes can digest cellulose, and many herbivores have symbiotic
relationships with these microbes
•
Cows have some of the cellulosedigesting microbes in their rumens
(1st compartment of stomach)
–
•
These prokaryotes hydrolyze
cellulose in hay and grass and
convert the glucose into other nutrients for the cow
Termites also have these prokaryotes living in their guts, allowing them to eat
wood
•
Another important structural polysaccharide is chitin – a carbohydrate used by arthropods
(insects, spiders, crustaceans)
–
It is used to build their exoskeletons, protecting the soft parts of these animals
•
Pure chitin is leathery and flexible but it becomes hardened when encrusted with
calcium carbonate
–
Chitin is also found in many fungi, which use this polysaccharide rather than cellulose
as the structural component of their cell walls
Concept Check 5.2
• 1) Write the formula for a monosaccharide that has 3
carbons.
• 2) A dehydration reaction joins 2 glucose molecules to
form maltose. The formula for glucose is C6H12O6.
What is the formula for maltose?
• 3) What would happen if a cow were given antibiotics
that killed all the prokaryotes in its stomach?
Concept 5.3:
Lipids are a diverse group of
hydrophobic molecules
• Lipids are not true polymers and they are generally not big enough to
be called macromolecules
– They are grouped together because they all mix poorly, if at all,
with water due to their structure
• Although some may contain polar bonds associated with
oxygen, they consist mostly of hydrocarbon regions
– Lipids include fats, phospholipids, steroids, waxes, and certain
pigments
Fats
•
Fats are large molecules assembled from a few smaller molecules by dehydration reactions,
mainly glycerol and fatty acids
–
Glycerol is an alcohol with 3 carbons, each attached to a hydroxyl group
–
A fatty acid is made up of a long carbon
skeleton, usually 16-18 carbons in
length
•
The carbon at one end of the fatty acid
is part of a carboxyl group, giving this
group the name fatty “acid”
•
The relatively nonpolar C-H bonds in the hydrocarbon chains are the reason they are
hydrophobic
–
•
Fats separate from water because water
molecules H-bond to one another instead of
the fats
To make a fat, 3 fatty acids each join to glycerol by
an ester linkage (bond between hydroxyl and
carbonyl group)
–
The resulting fat is called a triaglycerol or
triglyceride
•
•
a) Dehydration reaction in the synthesis of a fat
–
•
Fatty acids making up a fat can be the
same or they can be 2 or 3 different kinds
One water molecule is removed for each
fatty acid joined to the glycerol
b) Triglycerol – a fat molecule
•
Fatty acids vary in length and in the number and locations of double bonds
–
Saturated fatty acids – do not contain any double bonds and so as many
hydrogen atoms as possible are bonded to carbon skeleton (“saturated” with
hydrogen)
–
Unsaturated fatty acids – have one or more double
bonds, formed by the removal of hydrogen atoms from
the carbon skeleton
• As a result, the fatty acid will have a kink in its
hydrocarbon chain wherever a cis double bond
occurs
Animation: Fats
•
Fats made from saturated fatty acids are called saturated fats
–
Most animal fats are saturated
– Ex) Butter and lard
• Because the hydrocarbon chains of their
fatty acids (tails of the fat molecule) lack
double bonds, rotation about the C-H
bonds is permitted
– This flexibility allows the fat
molecules to pack tightly together,
making them solid at room
temperature
•
Fats of plants and fish are generally unsaturated in contrast, and are therefore called
unsaturated fats
–
Because they are usually liquid at room temperature,
they are referred to as oils (olive oil, cod oil)
•
Kinks where cis double bonds are located prevent
the molecules from packing together closely
enough to solidify at room temperature
–
Hydrogenated vegetable oils seen on food labels mean
that unsaturated fats have been synthetically converted
to saturated fats by adding hydrogen
–
•
Ex) Peanut butter and margarine
They are saturated to prevent their lipids from
separating out in liquid form
•
Diets rich in saturated fats are one of many factors that contribute to cardiovascular
disease called atherosclerosis
–
In this condition, deposits called plaques develop within the walls of blood
vessels
• This, in turn, causes inward bulges that impede blood flow and reduce the
resilience of vessels
–
We have also recently discovered that the process of hydrogenating vegetable
oils produces not only saturated fats but also unsaturated fats with trans double
bonds (trans fats)
• These trans fats may contribute more than saturated fat to artherosclerosis
– Trans fats are common in baked goods and processed foods
•
Despite their negative connotations, fats actually serve a very useful purpose
–
The major function of fats is energy storage
•
Hydrocarbon chains of fats are similar to gasoline molecules and just as rich in
energy
•
A gram of fat actually stores 2X as much energy as a gram of a polysaccharide
(sugar)
–
Because animals must carry their energy stores with them (unlike plants which are
immobile), the more compact structure of a fat is ideal
•
Humans and other mammals stock their long-term food reserves in adipose cells
that swell and shrink as fat is deposited and withdrawn from storage
•
Adipose tissue also cushions vital organs like kidneys and a layer of fat under the
skin insulates the body
–
This subcutaneous layer is especially thick in many marine mammals
(whales, seals)
Phospholipids
•
Another essential type of lipid is the phospholipid, which makes up cell membranes
–
–
Phospholipids are similar to fat molecules but only have 2 fatty acids attached to
glycerol instead of 3
•
The 3rd hydroxyl group of glycerol is joined instead to a phosphate group with a
negative charge
•
Additional small molecules that are usually charged or polar can also be linked to
this phosphate group to form a variety of phospholipids
The 2 ends of a phospholipid exhibit different behaviors toward water
•
The hydrocarbon tails are
hydrophobic
•
The phosphate group and its
attachments form a hydrophilic
head with an affinity for water
•
When phospholipids are added to water, they self-assemble into double-layered
aggregations called bilayers that shield hydrophobic portions from water
–
In the phospholipid bilayer of cell membrane, the hydrophilic heads are on the
outside of the bilayer and in contact with the aqueous interior and exterior of
the cell
–
The hydrophobic tails point toward interior of bilayer, away from water
Steroids
•
Another class of lipids are steroids – lipids whose carbon skeleton consists of 4 fused rings
–
Different steroids have different chemical groups attached to their carbon skeleton rings
–
They include many hormones, as well as cholesterol
•
Cholesterol is a component of animal cell membranes and is also a precursor from
which other steroids are synthesized
–
In vertebrates, cholesterol is made in the liver
–
Many hormones (like vertebrate sex hormones) are steroids produced from
cholesterol
–
Although cholesterol is an essential
molecule, a high level of it can
also contribute to artherosclerosis
Concept Check 5.3
• 1) Compare the structure of a fat (triglyceride) with
that of a phospholipid.
• 2) Why are human sex hormones considered
lipids?
• 3) Suppose a membrane surrounded an oil droplet,
as it does in the cells of plant seeds. Describe and
explain the form it might take.
Concept 5.4:
Proteins have many structures,
resulting in a wide range of functions
•
Proteins account for more than 50% of the dry mass of most cells
–
They are instrumental in almost everything organisms do including:
•
Speeding up chemical reactions
•
Structural
support
•
Storage
•
Transport
•
Cellular
communication
•
Movement
•
Defense against foreign substances
Animation: Structural Proteins
Animation: Storage Proteins
Animation: Transport Proteins
Animation: Receptor Proteins
Animation: Contractile Proteins
Animation: Defensive Proteins
Animation: Hormonal Proteins
Animation: Sensory Proteins
Animation: Gene Regulatory Proteins
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
•
Most enzymes are proteins
–
–
Enzymes regulate metabolism by acting as catalysts
•
Catalysts are chemical agents that selectively speed up chemical reactions without
being consumed by the reaction
•
They can be thought of as workhorses that keep cells running by carrying out
processes of life because they can perform their functions again and again (they
are not consumed)
Ex) The enzyme sucrase accelerates hydrolysis of sucrose into glucose and fructose
•
Note that the sucrase is not consumed curing the reaction but remains available for
further catalysis
–
1)Active site is available for a molecule of substrate – the reactant on which
the enzyme acts
–
2)Substrate binds to enzyme
–
3)Substrate is converted to products
–
4)Products are released
Animation: Enzymes
Polypeptides
• Humans have 10s of 1000s of different proteins each with a specific
structure and function
– Despite their diversity, all proteins are made up of one or more
polymers constructed from the same set of 20 amino acids
• These polymers of amino acids are called polypeptides
– Each protein is folded and coiled into a specific 3-dimensional
structure
Amino Acid Monomers
•
Amino acids are organic molecules that have carboxyl and amino groups
–
All amino acids share a common structure
•
–
They differ only in a variable group R group (also called a side chain)
The general formula for an amino acid is shown below
•
At the center of each amino acid is an asymmetric carbon atom – called an alpha
carbon – which has 4 different partners:
–
Carboxyl group
–
Amino group
–
Hydrogen atom
–
Variable R group
•
20 different amino acids are used by cells to build their proteins (organisms do have
other amino acids that are occasionally found in proteins but they are relatively rare)
–
Amino acids here are shown in their prevailing
ionic forms at pH 7.2, the pH of the cell
–
The 3 letter and more commonly used
one-letter abbreviations for these amino acids
are also shown
–
All amino acids used in proteins are the same
enantiomer, called the L form (as
shown here)
•
Amino acids can be grouped according to the properties of their side chains (highlighted in
white)
–
Nonpolar amino acids – hydrophobic
–
Polar amino acids – hydrophilic
–
Acidic amino acids – side chains are generally
negative due to presence of a carboxyl group
which usually dissociates (ionizes) at
cellular pH
–
Basic amino acids – have amino groups in
their side chains and are generally positive
in charge
•
Because they are charged, acidic and basic
amino acids are also hydrophilic
•
***Note: All amino acids have a carboxyl
group and an amino group – the terms
acidic and basic in this context refer only
to groups on side chains
Amino Acid Polymers
•
Amino acids are linked together to form polymers using covalent peptide bonds
–
They become joined by a dehydration reaction when 2 amino acids are positioned so
that the carboxyl group of one amino acid is next to the amino group of the other
•
–
This process is repeated over and over and results in a polypeptide
At one end of resulting polypeptide chain is a free amino group and is therefore called
the N-terminus
•
The opposite end is a free carboxyl group and
is called the C-terminus
–
Polypeptides vary in length from a few monomers to
1000s
•
Each has a specific sequence of amino acids,
using a limited set of monomers to make many
different combinations
Protein Structure and Function
•
The activities of proteins are due to their 3-dimensional structure
–
•
The simplest level of structure is a protein’s amino acid sequence
Note: The term polypeptide is not synonymous with the word protein (Just as a long
strand of yarn and a sweater of a particular shape and size are not the same)
–
A functional protein is not JUST a polypeptide chain, but one or more
polypeptides precisely twisted, folded, and coiled into a molecule of unique
shape
–
The amino acid sequence of each polypeptide does, however, determine what
3-dimensional structure the protein will have
•
Lysozyme is an enzyme present in sweat, tears, and saliva
–
It helps prevent infection by binding to and destroying specific molecules on the
surface of many kinds of bacteria
•
A) A ribbon model shows how the single polypeptide chain folds and coils to form the
functional protein
–
Yellow lines represent cross-linking bonds between cysteines that stabilize the protein‟s
shape
•
B) A space-filling model shows the globular shape seen in many proteins more clearly
–
The groove is the part of
that recognizes and bonds
the target molecules on
bacterial walls
the protein
•
When a cell makes a polypeptide, the chain usually forms spontaneously and is
driven and reinforced by formation of different bonds between parts of the chain
•
–
Many proteins are roughly spherical – called globular proteins
•
–
This in turn, depends on the sequence of amino acids
Others are shaped like long fibers – called fibrous proteins
A protein‟s specific structure determines how it works
•
Functions of proteins in most cases
depend on their ability to recognize
and bind to some other molecule
•
This fit is very specific, like a lock and
key
– Ex) Lysozyme (previous)
–
Ex) Virus and antibody (right)
Four Levels of Protein Structure
• All proteins share 3 superimposed levels of structure
– Primary: sequence of amino acids
– Secondary: consists of coils and folds in polypeptide chain
– Tertiary: determined by interactions amoung R groups
– Quaternary : a 4th level that arises when a protein consists
of 2 or more polypeptide chains
Animation: Protein Structure Introduction
Primary Structure
• Primary Structure – a protein‟s unique sequence of amino acids
–
This is comparable to the order of letters in a very long word
–
To figure out how many different way there are to arrange a
particular sequence of amino acids:
20 ^ (# of AA in protein)
–
The precise primary structure of a protein is not determined at
random but by inherited genetic information
Animation: Primary Protein Structure
Secondary Structure
•
A protein‟s secondary structure results from coiling and folding of segments of their
polypeptide chains
–
This folding and coiling is the result of H-bonds between repeating parts of
polypeptide backbone (not the amino acid side chains)
•
Any oxygen and nitrogen atoms of the backbone are electronegative (have
partial negative charges),
–
Thus, the weakly positive hydrogen atom attached to a nitrogen atom
has an affinity for the oxygen atom of a nearby peptide bond
•
Individually, these H-bonds are weak,
–
Because they are repeated many times over a large portion of the
polypeptide chain, however, they can support a protein‟s particular
shape
Animation: Secondary Protein Structure
Common Secondary Structure: Alpha Helix
•
Some common secondary structures:
–
1) Alpha helix – coil held together by H-bonding between every 4th amino acid
•
Some proteins may have only a single stretch of an alpha helix (ex:
transthyretin)
•
Others have multiple
stretches of these helices
separated by nonhelical
regions
•
Still others (ex: alphakeratin, the structural
component of hair) have alpha helix formation over most of their length
Common Secondary Structure: Beta Pleated Sheet
•
Some common secondary structures:
–
2) Beta pleated sheet – 2 or more regions of
polypeptide chain lying side by side are connected by
H-bonds between parts of the 2 parallel polypeptide
backbones
•
Pleated sheets make up the core of many
globular proteins (like transthyretin)
•
They also make up large portions
of many fibrous proteins
(including silk proteins of
spider webs)
Animation: Secondary Protein Structure
Tertiary Structure
• The tertiary structure of a protein is superimposed on the
patterns of secondary structure
– This level gives the overall shape of the polypeptide
• It is due to interactions between side chains (R groups)
of various amino acids (not between interactions of
backbone like in secondary structure)
Animation: Tertiary Protein Structure
Tertiary Structure: Interactions
•
Types of Interactions Contributing to Tertiary Structure:
–
–
1) Hydrophobic interaction – as polypeptide folds into its functional shape,
amino acids with hydrophobic (nonpolar) side chains usually end up in clusters
at core of protein, out of contact with water
•
Once nonpolar amino acid side chains are close together, van der Waals
interactions help hold them together
•
At the same time, H-bonds between polar side chains and ionic bonds
between positively and negatively
charged side chains also help stabilize
tertiary structure
2) Disulfide bridges – covalent bonds
between sulfur atoms that form when
2 cysteine monomers (AAs containing
sulfhydyl groups –SH) are brought close
together by folding of protein
•
Bonds 2 parts of a protein together
Quaternary Structure
•
When proteins consist of 2 or more polypeptide chains, a 4th level of organization is
required
–
•
Quaternary structure is the overall protein structure
that results from the aggregation of these
polypeptide subunits
Examples of quaternary structure include:
–
–
1) Collagen: a fibrous protein consisting of 3
polypeptides coiled like a rope
•
Collagen supports connective tissue in the skin, bone, tendons, ligaments,
and other body parts
•
It makes up 40% of all proteins in the human body
2) Hemoglobin: a globular protein consisting of 4 polypeptides: 2 alpha and 2
beta chains
•
Hemoglobin is the oxygen-binding
protein of red blood cells
Animation: Quaternary Protein Structure
•
Figure 5.21 Levels of protein structure
–
Ex) Transthyretin – globular protein found in blood that transports
vitamin A and one of the thyroid hormones throughout the body
• Made of 4 identical polypeptide chains totaling 127 amino acids
• 20^127 possible sequences
Sickle-Cell Disease: A Change in Primary Structure
•
Even a slight change in primary structure can affect a protein‟s shape and function
–
Ex) Sickle Cell Anemia: an inherited blood disorder
•
It is caused by substitution of one amino acid (valine) for the normal amino
acid (glutamic acid) in the primary structure of hemoglobin
–
–
Recall: hemoglobin is the protein that carries oxygen in RBCs
Normal RBC are disk-shaped
•
In sickle cell disease, the
abnormal hemoglobin
molecules tend to crystallize,
deforming some of the cells
into a sickle shape
•
These angular cells clog tiny
blood vessels and impede
blood flow
–
This results in a reduced
capacity to carry oxygen
What Determines Protein Structure?
•
In additional to the levels of protein structure already discussed, a protein‟s shape
can also be influenced by the physical and chemical conditions of the protein‟s
environment
–
Changes in any of the following conditions can cause a protein to unravel and
lose its native shape, a process called denaturation
–
•
pH
•
Salt concentration
•
Temperature
•
Other environmental factors
Because a protein‟s shape is essential to its function, denatured proteins are
biologically inactive
What Determines Protein Structure?
•
Proteins can become denatured if:
–
They are transferred from an aqueous environment to organic solvent (ex:
ether, chloroform)
•
The polypeptide chain refolds so hydrophobic regions face outside toward
solvent
–
They are exposed to chemicals that disrupt H-bonds, ionic bonds, and disulfide
bridges
–
They are excessively heated
•
Heat agitates the polypeptide chain enough to overpower the weak
interaction that stabilize protein structure
–
Ex) egg whites becomes opaque during cooking because denatured
proteins are insoluble and solidify
Renaturation of Proteins
•
High temperature or various chemical treatment will denature a protein, causing it to
lose its shape and hence its ability to function
–
If denatured protein remains dissolved, it can often renature when the chemical
and physical aspects of its environment are restored to normal
–
We can therefore conclude that the information for building a specific shape is
intrinsic in protein‟s primary structure – its sequence of amino acids will
determine protein‟s shape
Protein Folding in the Cell
•
Most proteins probably go through several intermediate structures on their way to a
stable shape
–
In the crowded environment of the cell, there are specific proteins that aid in the
folding of other proteins
•
These protein molecules that assist in proper folding of other proteins are
called chaperonins (or chaperone proteins)
•
Chaperonins do not specify final protein structure, but they keep the
polypeptides segregated from “bad” influences in the cytoplasm while it
folds spontaneously
–
Misfolding of proteins is a serious problem
•
Alzheimer‟s and Parkinson‟s are associated with an accumulation of
misfolded proteins
•
•
This computer graphic below shows a large chaperonin-protein complex
–
It has an interior space that provides a shelter for the proper folding of newly
made polypeptides
–
The complex consists of 2 proteins:
•
1) One protein is a hollow cylinder
•
2) The other is a cap that can fit on either end
Steps of Chaperonin Action:
–
1)An unfolded polypeptide enters cylinder from one end
–
2)The cap attaches, causing the cylinder to change shape in such a way that it
creates a hydrophilic environment
for the folding of
the polypeptide
–
3)The cap
comes off and
the properly folded
protein is released
• Determining the exact 3-dimensional structure of a protein is not
simple because a single protein molecule is made up of 1000s of
atoms
–
One method scientists have used to work out the 3D structures
for proteins such as hemoglobin (1959) is X-ray
crystallography
–
Another method is nuclear magnetic resonance (NMR) which
does not require protein crystallization
–
A more recent approach uses bioinformatics to predict the 3-D
structures of polypeptides from their amino acid sequences
•
What can the 3-D shape of the enzyme RNA polymerase II tell us about its function?
–
Experiment: Roger Kornberg used X-ray crystallography to determine the
shape of RNA polymerase II, which binds to the DNA double helix and makes
RNA
•
After crystallizing a complex of all 3 components (DNA, RNA, RNA
polymerase), an X-ray beam was aimed through the crystal
•
Atoms that the crystal diffracted (bent) the X-rays into an orderly array that
a digital detector recorded as a pattern of spots called an X-ray diffraction
pattern
–
Results: Using the x-ray diffraction patterns
and amino acid sequences already
determined by chemical methods, Kornberg
built a 3-D model of the complex with the
help of computer software (see picture)
–
Conclusion: By analyzing the model,
researchers developed a hypothesis about
the functions of different regions of RNA polymerase
II (such as region above DNA may act as a
clamp that holds nucleic acids in place
during transcription)
Concept Check 5.4
• 1) Why does a denatured protein no longer
function normally?
• 2) What parts of a polypeptide chain participate in
the bonds that hold together secondary structure?
What parts participate in tertiary structure?
• 3) If a genetic mutation changes primary structure,
how might it destroy the protein‟s function?
Concept 5.5:
Nucleic acids store and transmit
hereditary information
• The amino acid sequence of a polypeptide is
programmed by a unit of inheritance called a gene
– Genes are made of DNA, a polymer belonging to a
class of compounds called nucleic acid
The Roles of Nucleic Acids
•
There are 2 types of nucleic acids: DNA (deoxyribonucleic acid) and RNA
(ribonucleic acid)
• These nucleic aids allow living organisms to reproduce from one
generation to the next
–
Unlike other molecules, DNA provides directions for its own replication
• DNA also directs RNA synthesis (transcription) and, using RNA as
an intermediate, controls protein synthesis (translation)
• The sites of protein synthesis are tiny structures called ribosomes,
found in the cytoplasm of the cell
•
Figure 5.26: DNA → RNA → protein
–
Each gene along a DNA molecule directs the synthesis of a type of RNA
molecule called messenger RNA (mRNA)
•
This process is called
transcription
–
mRNA then directs the production
of a polypeptide, which then folds
into a protein
•
–
This process is called translation
We can summarize the flow of
genetic information as:
DNA – RNA – Protein
The Structure of Nucleic Acids
•
Nucleic acids exist as polymers called polynucleotides
–
Each polynucleotide is made up of monomers called nucleotides
• A nucleotide is composed of 3 parts:
– Nitrogenous base
– 5-carbon sugar (pentose)
– Phosphate group
–
The portion of a nucleotide without the phosphate group is called a
nucleoside
•
a) A polynucleotide has a sugar phosphate backbone with different attachments, the
nitrogen bases
•
b) A nucleotide monomer includes a nitrogenous base, a sugar, and a phosphate
group
–
•
Without the phosphate group, the structure is called a nucleoside
c) A nucleoside includes a nitrogenous base (purine or pyrimidine) and a 5-carbon
sugar (deoxyribose or ribose)
–
***Because the
atoms in both the
nitrogenous base
and the sugar are
numbered, the
sugar atoms have
a prime („) after the
number to
distinguish them
Nucleotide Monomers
•
There are 2 families of nitrogenous bases:
–
Pyrimidines: 6-membered ring of carbon and nitrogen atoms
•
Members of the pyrimidine family are cytosine (C), thymine (T), and uracil
(U)
–
Purines: 6-membered ring fused to a 5-membered ring
•
–
Include adenine (A) and guanine (G)
Specific pyrimidines and purines differ only in the chemical groups attached to
the rings
•
The nitrogen atoms tend to take up H+ ions from solution, which is why they are
called nitrogenous BASES
Nucleotide Monomers
•
•
A, G, and C are found in both DNA and RNA
–
Thymine is found only in DNA
–
Uracil is found only in RNA
The sugar connected to the nitrogenous base differs depending on the
nucleic acid:
–
Ribose in RNA
–
Deoxyribose in DNA
• The only difference between the 2 sugars is that deoxyribose lacks
an oxygen atom on the 2nd carbon in the ring (hence
DEOXYribose)
Nucleotide Polymers
•
Adjacent nucleotides are joined by a phosphodiester linkage to build
polynucleotides
–
This consists of a phosphate group that links the sugars of the 2 nucleotides
•
Adjacent nucleotides are joined by covalent bonds that form between the
–OH group on the carbon of one nucleotide and the phosphate of the next
carbon
•
This bonding
results in a
backbone with a
repeating pattern
of sugarphosphate units
•
The 2 free ends are distinctly different from each other
–
One end has a phosphate attached to a 5‟ carbon
–
Other end has a hydroxyl group on the 3‟ carbon
•
–
•
We refer to these as 5‟ and 3‟ ends, respectively
We can say that DNA has a built-in directionality along its sugar-phosphate
backbone, from 5‟ to 3‟
The sequence of bases along DNA or mRNA is different for each gene
–
A gene‟s meaning to the cell is
thus encoded in this specific
sequence of the four bases of
DNA and mRNA
–
The linear order of bases in a
gene specifies the amino acid
sequence (primary structure) of
a protein, which in turn
specifies the protein‟s 3-D
structure and function
The DNA Double Helix
•
DNA molecules consist of 2 polynucleotides that spiral around an imaginary axis,
forming a double helix
–
The 2 sugar-phosphate backbones run in opposite 5‟ to 3‟ directions from each
other,
•
–
This arrangement is referred to as antiparallel (like a divided highway)
The sugar phosphate backbones are on the outside of the helix and nitrogen
bases are paired in the interior of the helix
•
The 2 strands of polynucleotides are
held together by H-bonds between the
paired bases and by van der Waals
interactions between stacked bases
–
Most DNA molecules are very long , made
of 1000s to millions of base pairs and
many genes
The DNA Double Helix
•
Only certain bases in the double helix are compatible with each other
–
A always pairs with T
–
G always pairs with C
•
The 2 strands are thus complementary
to each other, each a predictable
counterpart of the other
•
In preparation for cell division, the 2 strands of the DNA
molecule separate and both serve as a template to
order nucleotides into a new complementary strand
–
The result is 2 identical copies of the
original double-stranded DNA
molecule, which are then
distributed to the 2 daughter cells
DNA and Proteins as Tape Measures of Evolution
•
Genes and their proteins document the hereditary background of an organism
–
The linear sequences of nucleotides in DNA are passed from parent to
offspring
•
–
Siblings have a greater similarity in DNA and proteins than do unrelated
individuals of the same species
This concept of molecular “geneology” also extends to relationships between
species
•
2 species that are closely related share a greater proportion of their DNA
and protein sequences than more distantly related species
–
Ex) Comparison of polypeptide chain of human hemoglobin with 5
other vertebrates:
•
Out of 146 amino acids, humans and gorillas differ only by 1
amino acid
•
Humans and frogs differ in 67 amino acids
Concept Check 5.5
•
1) Go to Figure 5.27a (pp. 87) and number all the carbons in the sugars for the top 3
nucleotides; circle the nitrogenous bases and star the phosphates.
•
2) In a DNA double helix, a region along one DNA strand has this sequence of
nitrogenous bases: 5‟-TAGGCCT-3‟. Write down this strand and its complementary
strand, clearly indicating the 5‟ and 3‟ ends of the complementary strand.
•
3) (a) Suppose a substitution occurred in one DNA strand of the double helix in
question 2, resulting in:
5‟-TAAGCCT-3‟
3‟-ATCCGGA-3‟
Draw the 2 strands; circle and label the mismatched bases
(b) If the modified top strand is replicated, what would be its matching stand be?
The Theme of Emergent Properties in the Chemistry
of Life: A Review
• Life is organized along a hierarchy of structural levels
– With each increasing level of order, new properties
emerge
– In the next unit, we will study the next level of
organization, cell structure and function
Fig. 5-UN2a
Fig. 5-UN2b
You should now be able to:
1. List and describe the four major classes of
molecules
2. Describe the formation of a glycosidic linkage
and distinguish between monosaccharides,
disaccharides, and polysaccharides
3. Distinguish between saturated and
unsaturated fats and between cis and trans fat
molecules
4. Describe the four levels of protein structure
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
You should now be able to:
5. Distinguish between the following pairs:
pyrimidine and purine, nucleotide and
nucleoside, ribose and deoxyribose, the 5
end and 3 end of a nucleotide
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings