Transcript Chapter 4 - Large Bio Molecules

Chapter 5: The Structure and Function of
Macromolecules
1)
Polymer formation – large molecules (macromolecules) make up
most things in the cell
2)
Types of polymers
1)
Carbohydrates – sugars (mono- di- and poly-saccharides)
2)
Lipids are macromolecules that do NOT form polymers – fats
and phospholipids
3)
Proteins – function, structure, conformation, folding.
4)
1)
Simple protein changes can cause disease
2)
Determination of protein structure
Nucleic Acids – DNA and RNA
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: The Molecules of Life
•
Within cells, small organic molecules are joined together to form larger
molecules
•
Macromolecules are large molecules composed of thousands of
covalently connected atoms
•
Most macromolecules are polymers, built from monomers
•
A polymer is a long molecule consisting of many similar building
blocks called monomers
•
Three of the four classes of life’s organic molecules are polymers:
–
Carbohydrates
–
Proteins
–
Nucleic acids
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Synthesis and
Breakdown of Polymers
Short polymer
Unlinked monomer
Dehydration removes a water
molecule, forming a new bond
•Monomers form larger
molecules by condensation
reactions called dehydration
reactions (they release free water
molecules)
•Polymers are disassembled to
monomers by hydrolysis, a
reaction that is essentially the
reverse of the dehydration
reaction (water actually breaks
the bonds between individual
monomers)
Longer polymer
Dehydration reaction in the synthesis of a polymer
Hydrolysis adds a water
molecule, breaking a bond
Hydrolysis of a polymer
The Diversity of Polymers: Many different types!
•
Each cell has thousands of different kinds of macromolecules
•
Macromolecules vary among cells of an organism, vary more within a
species, and vary even more between species
•
An immense variety of polymers can be built from a small set of
monomers
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Carbohydrates serve as fuel and building material
•
Carbohydrates include sugars and the polymers of sugars
•
The simplest carbohydrates are monosaccharides, or single sugars
•
–
Monosaccharides have molecular formulas that are usually
multiples of CH2O
–
Glucose is the most common monosaccharide
–
Monosaccharides are classified by location of the carbonyl group
and by number of carbons in the carbon skeleton
Carbohydrate macromolecules are polysaccharides, polymers
composed of many sugar building blocks
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Sugars
•
Monosaccharides serve as a major fuel for cells and as raw material
for building molecules
•
Though often drawn as a linear skeleton, in aqueous solutions they
form rings
Linear and
ring forms
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Abbreviated ring
structure
Disaccharide formation
•
A disaccharide is formed when a dehydration reaction joins two
monosaccharides
•
This covalent bond is called a glycosidic linkage
Dehydration
reaction in the
synthesis of maltose
1–4
glycosidic
linkage
Glucose
Glucose
Dehydration
reaction in the
synthesis of sucrose
Maltose
1–2
glycosidic
linkage
Glucose
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fructose
Sucrose
Polysaccharides
•
Polysaccharides, the polymers of sugars, have storage and structural
roles
•
The structure and function of a polysaccharide are determined by its
sugar monomers and the positions of glycosidic linkages between the
individual sugar monomers that build the polymer
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Storage Polysaccharides: Starch
•
Starch, a storage
polysaccharide of plants,
consists entirely of
glucose monomers
•
Plants store surplus
starch as granules within
chloroplasts and other
plastids
Chloroplast
Starch
1 µm
Amylose
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Amylopectin
Starch: a plant polysaccharide
Storage Polysaccharides: Glycogen
Mitochondria Glycogen granules
•
Glycogen is a storage
polysaccharide in animals
•
Humans and other
vertebrates store glycogen
mainly in liver and muscle
cells
0.5 µm
Glycogen
Glycogen: an animal polysaccharide
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Structural Polysaccharides: Cellulose
•
Cellulose is a major
component of the tough
wall of plant cells
•
Like starch, cellulose is a
polymer of glucose, but the
glycosidic linkages differ
•
The difference is based on
two ring forms for glucose:
alpha () and beta ()
•
Polymers consisting of 
glucose form starch
•
a Glucose
b Glucose
a and b glucose ring structures
Starch: 1–4 linkage of a glucose monomers.
Polymers consisting of 
glucose form cellulose
Cellulose: 1–4 linkage of b glucose monomers.
Cellulose
Cellulose microfibrils
in a plant cell wall
Cell walls
Microfibril
•Polymers with alpha
glucose are helical
•Polymers with beta
glucose are straight
0.5 µm
•In straight structures, Plant cells
H atoms on one strand
can bond with OH
groups on other
strands
•Parallel cellulose
molecules held
together this way are
grouped into
microfibrils, which form
strong building
materials for plants
Cellulose
molecules
 Glucose
monomer
Breakdown of cellulose
•
Enzymes that digest starch by hydrolyzing alpha linkages can’t
hydrolyze beta linkages in cellulose
•
Cellulose in human food passes through the digestive tract as
insoluble fiber
•
Some microbes use enzymes to digest cellulose
•
Many herbivores, from cows to termites, have symbiotic relationships
with these microbes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Chitin
•
Chitin, another structural polysaccharide, is found in the exoskeleton of
arthropods
•
Chitin also provides structural support for the cell walls of many fungi
•
Chitin can be used as surgical thread
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Lipids are a diverse group of hydrophobic
molecules
•
Lipids are the one class of large biological molecules that do not form
polymers
•
The unifying feature of lipids is having little or no affinity for water
•
Lipids are hydrophobic because they consist mostly of hydrocarbons,
which form nonpolar covalent bonds
•
The most biologically important lipids are fats, phospholipids, and
steroids
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fats
•
Fats are constructed from two types of smaller molecules: glycerol and
fatty acids
•
Glycerol is a three-carbon alcohol with a hydroxyl group attached to
each carbon
•
A fatty acid consists of a carboxyl group attached to a long carbon
skeleton
Fatty acid
(palmitic acid)
Glycerol
Dehydration reaction in the synthesis of a fat
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fats are hydrophobic molecules
•
Fats separate from water because water molecules form
hydrogen bonds with each other and exclude the fats
•
The long hydrocarbon chains of fatty acids are unable to form any
hydrogen bonds with the water molecules and are thus
hydrophobic
•
In a fat, three fatty acids are joined to glycerol by an ester linkage,
creating a triacylglycerol, or triglyceride
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fat molecule (triacylglycerol)
Ester linkage
Types of fats
•
Fatty acids vary in length (number of carbons in the hydrocarbon
chain) and in the number and locations of double bonds in the chain
•
Saturated fatty acids have the maximum number of hydrogen atoms
possible and no double bonds
•
Unsaturated fatty acids have one or more double bonds
•
The major function of fats is energy storage
•
Fats made from saturated fatty acids are called saturated fats
•
Most animal fats are saturated
•
Saturated fats are solid at room temperature
•
A diet rich in saturated fats may contribute to cardiovascular disease
through plaque deposits
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Saturated fats are not so good for you!!
Stearic acid
Saturated fat and fatty acid.
Unsaturated fats
•Fats made from unsaturated fatty acids are called unsaturated fats
•Plant fats and fish fats are usually unsaturated
•Plant fats and fish fats are liquid at room temperature and are called oils
Oleic acid
Unsaturated fat and fatty acid.
cis double bond
causes bending
Phospholipids
•In a phospholipid, two fatty acids and a phosphate group are attached to glycerol
•The two fatty acid tails are hydrophobic, but the phosphate group and its attachments
form a hydrophilic head
Choline
Phosphate
Glycerol
Fatty acids
Hydrophilic
head
Hydrophobic
tails
Structural formula
Space-filling model
Phospholipid symbol
Phospholipids behavior in water
•
When phospholipids are added to water, they self-assemble into a
bilayer, with the hydrophobic tails pointing toward the interior
•
They also may assemble into a micelle – a sperical shaped
arrangement of phospholipids where the hydrophobic tails all point into
the center of the sphere
•
The structure of phospholipids results in a bilayer arrangement found in
cell membranes
•
Phospholipids are the major component of all cell membranes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The structure of a typical phospholipid bilayer:
cell membranes
Hydrophilic
head
Hydrophobic
tails
WATER
WATER
Steroids
•
Steroids are lipids characterized by a carbon skeleton consisting of
four fused rings
•
Cholesterol, an important steroid, is a component in animal cell
membranes
•
Although cholesterol is essential in animals, high levels in the blood
may contribute to cardiovascular disease
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Proteins have many structures, resulting in a wide
range of functions
•
Proteins account for more than 50% of the dry mass of most cells
•
Protein functions include structural support, storage, transport, cellular
communications, movement, and defense against foreign substances
•
Proteins are what does the ‘business’ of the cell – they are responsible
for carrying out almost all of the essential biochemical reactions and
processes that contribute to life
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
What do proteins do? A more appropriate question
may be what don’t proteins do!
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein functions: Enzymes
•
Enzymes are a type of protein that acts as a catalyst, speeding up
chemical reactions
•
Enzymes can perform their functions repeatedly, functioning as
workhorses that carry out the processes of life
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein functions:
Enzymes
Substrate
(sucrose)
Glucose
Enzyme
(sucrase)
Fructose
Proteins are built from and sometimes called
Polypeptides
•
Polypeptides are polymers of amino acids
•
A protein consists of one or more polypeptides
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Amino Acid Monomers
•
Amino acids are the ‘building blocks’ of proteins
•
Amino acids are organic molecules with carboxyl and amino groups
•
Amino acids differ in their properties due to differing side chains, called
R groups
•
Cells use 20 amino acids (of three main classes) to make thousands of
proteins
 carbon
Amino
group
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Carboxyl
group
Amino Acid Polymers
•
Amino acids are linked together by peptide bonds to form the
polypeptides that comprise a protein
•
Polypeptides range in length from a few amino acids monomers to
more than a thousand
•
Each polypeptide has a unique linear sequence of amino acids
•
The amino acid sequences of polypeptides were first determined by
chemical methods
•
Most of the steps involved in sequencing a polypeptide are now
automated
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Four Levels of Protein Structure
•
The primary structure of a protein is simply its unique sequence of
amino acids
•
Secondary structure, found in most proteins, consists of coils and
folds in the polypeptide chain
•
Tertiary structure is determined by interactions among various side
chains (R groups) to yield a fully folded single polypeptide protein
•
Quaternary structure results when a protein consists of multiple
polypeptide chains, or multiple proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Four Levels of Protein Structure
 pleated sheet
+H
3N
Amino end
Amino acid
subunits
 helix
Primary
Secondary
Tertiary**
**Quaternary if there are more than one polypeptide chain
present in the final protein structure
Primary Structure
Amino end
Amino acid
subunits
Primary structure, the sequence of
amino acids in a protein, is like the
order of letters in a long word
Primary structure is determined by
inherited genetic information
Carboxyl end
Secondary Structure
•The coils and folds of secondary structure result from hydrogen bonds between
repeating constituents of the polypeptide backbone
•Typical secondary structures are a coil called an alpha helix and a folded
structure called a beta pleated sheet
 pleated sheet
Amino acid
subunits
 helix
Tertiary Structure
•
Tertiary structure is determined
by interactions between R
groups, rather than interactions
between backbone constituents
•
These interactions between R
groups include hydrogen bonds,
ionic bonds, hydrophobic
interactions, and van der Waals
interactions
•
Strong covalent bonds called
disulfide bridges may reinforce
the protein’s conformation
Hydrophobic
interactions and
van der Waals
interactions
Polypeptide
backbone
Hydrogen
bond
Disulfide bridge
Ionic bond
Quaternary Structure
•
Quaternary structure results when two or more polypeptide chains form
one macromolecule
•
Collagen is a fibrous protein consisting of three polypeptides coiled like
a rope
•
Hemoglobin is a globular protein consisting of four polypeptides: two
alpha and two beta chains
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Quaternary Structure
Polypeptide
chain
 Chains
Iron
Heme
Polypeptide chain
Collagen
 Chains
Hemoglobin
Protein Conformation and Function
•
•
A functional protein consists
of one or more polypeptides
twisted, folded, and coiled
into a unique shape
The sequence of amino
acids determines a protein’s
three-dimensional
conformation
•
A protein’s conformation
determines its function
•
Ribbon models and spacefilling models can depict a
protein’s conformation
Groove
A ribbon model
Groove
A space-filling model
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
What Determines Protein Conformation?
•
In addition to primary structure, physical and chemical conditions can
affect conformation of the folded protein
•
Alternations in pH, salt concentration, temperature, or other
environmental factors can cause a protein to unravel (unfold)
•
This loss of a protein’s native conformation is called denaturation
•
A denatured protein is biologically inactive
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Protein-Folding Problem
•It is hard to predict a protein’s conformation based solely on its primary structure
•Most proteins probably go through several states on their way to a stable
conformation
•Chaperonins are protein molecules that assist the proper folding of other
proteins
Denaturation
Denatured protein
Normal protein
Renaturation
Sickle-Cell Anemia Disease: A Simple Change in
Primary Structure affects the proteins function
•
A slight change in primary structure (the amino acid sequence of the
protein) can affect a protein’s conformation and ability to function
•
Sickle-cell disease, an inherited blood disorder, results from a single
amino acid substitution in the protein hemoglobin
10 µm
Red blood Normal cells are
cell shape full of individual
hemoglobin
molecules, each
carrying oxygen.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
10 µm
Red blood
cell shape
Fibers of abnormal
hemoglobin deform
cell into sickle
shape.
Sickle-Cell Anemia Disease: A Simple Change in
Primary Structure affects the proteins function
Sickle-cell hemoglobin
Normal hemoglobin
Primary
structure
Val
His
Leu
Thr
Pro
Glu
Glu
1
2
3
4
5
6
7
Secondary
and tertiary
structures
 subunit
Function
Secondary
and tertiary
structures
Molecules do
not associate
with one
another; each
carries oxygen.
His
Leu
Thr
Pro
Val
Glu
1
2
3
4
5
6
7
Exposed
hydrophobic
region
 subunit

Quaternary
structure

Val


Quaternary Normal
hemoglobin
structure
(top view)
Primary
structure
Sickle-cell
hemoglobin


Function
Molecules
interact with
one another to
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.


How can you determine a protein’s tertiary or
quaternary structure?
•
Scientists use X-ray crystallography to determine a protein’s
conformation
•
Another method is nuclear magnetic resonance (NMR) spectroscopy,
which does not require protein crystallization
X-ray
diffraction pattern
Photographic film
Diffracted X-rays
X-ray
source
X-ray
beam
Crystal
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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 nucleic acid
•
There are two types of nucleic acids:
–
Deoxyribonucleic acid (DNA), which we already discussed
–
Ribonucleic acid (RNA)
•
DNA provides directions for its own replication – it serves as a template
so it is replicated with each cell division
•
Messenger RNA (mRNA) is synthesized (transcribed) from DNA
•
Protein synthesis (translation) occurs in ribosomes from the mRNA
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
•The central dogma
of molecular biology
•Genetic information is
stored in DNA.
•This genetic information is
maintained by replication
DNA
Synthesis of
mRNA in the nucleus
mRNA
NUCLEUS
CYTOPLASM
•This information is
transcribed into RNA.
•The information is then
finally ‘read’ and
translated into proteins
•These proteins are
responsible for most
of the biochemical
reactions in the cell.
mRNA
Movement of
mRNA into cytoplasm
via nuclear pore
Ribosome
Synthesis
of protein
Polypeptide
Amino
acids
The Structure of
Nucleic Acids
5 end
•Nucleic acids are
polymers called
polynucleotides
Nucleoside
Nitrogenous
base
•Each polynucleotide
is made of monomers
called nucleotides
•Each nucleotide
consists of a
nitrogenous base, a
pentose sugar, and a
phosphate group
•The portion of a
nucleotide without the
phosphate group is
called a nucleoside
Phosphate
group
Nucleotide
3 end
Polynucleotide, or
nucleic acid
Pentose
sugar
Nitrogenous bases
Pyrimidines
Nucleotide Monomers
•Nucleotide monomers are made up of
nucleosides and phosphate groups
•Nucleoside = nitrogenous base + sugar
Cytosine
C
Thymine (in DNA) Uracil (in RNA)
U
T
•There are two families of nitrogenous bases:
Purines
• Pyrimidines have a single sixmembered ring
•Purines have a sixmembered ring fused to
a five-membered ring
Adenine
A
Guanine
G
Pentose sugars
•In DNA, the sugar is deoxyribose
•In RNA, the sugar is ribose
Deoxyribose (in DNA)
Nucleoside components
Ribose (in RNA)
Nucleotide Polymers
•
Nucleotide polymers are linked together, building a polynucleotide
•
Adjacent nucleotides are joined by covalent bonds that form between
the –OH group on the 3´ carbon of one nucleotide and the phosphate
on the 5´ carbon on the next
•
These links create a backbone of sugar-phosphate units with
nitrogenous bases as appendages
•
The sequence of bases along a DNA or mRNA polymer is unique for
each gene
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The DNA Double Helix – a review
•
A DNA molecule has two polynucleotides spiraling around an
imaginary axis, forming a double helix
•
In the DNA double helix, the two backbones run in opposite 5´ to 3´
directions from each other, an arrangement referred to as antiparallel
•
One DNA molecule includes many genes
•
The nitrogenous bases in DNA form hydrogen bonds in a
complementary fashion: A always with T, and G always with C
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
5 end
3 end
Sugar-phosphate
backbone
DNA replication occurs in a
Semi-conservative fashion
Base pair (joined by
hydrogen bonding)
Old strands
Nucleotide
about to be
added to a
new strand
5 end
New
strands
5 end
3 end
5 end
3 end
Similarities between DNA and RNA
•
They are both polymers
•
They are both built from four nucleotide monomers, three of which are
the same in each (A, C and G)
•
The are both synthesized and joined in a 5’ to 3’ fashion
•
Phosphodiester bonds connect the sugars in their backbones in the 5’
to 3’ linkage
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Differences between DNA and RNA
•
The sugar in the DNA backbone is deoxyribose, while it is ribose in
RNA
•
DNA is double stranded, while RNA is usually single stranded
•
DNA contains A, T, C, and G as its bases while RNA has A, U, C, and
G (it has uracil in place of tymine)
•
The 2’ OH group in ribose makes RNA MUCH more unstable and
reactive than DNA
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
DNA and Proteins as Tape Measures of Evolution
•
The linear sequences of nucleotides in DNA molecules are passed
from parents to offspring
•
Two closely related species are more similar in DNA than are more
distantly related species
•
Molecular biology can be used to assess evolutionary kinship
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings