Download Nucleic acids - Haiku Learning

Lesson 1:
Proteins
Proteins
Made of amino acids linked by peptide
bonds
There are 20 types of amino acids that
we use (though many more exist)
Be able to draw a
generalized amino
acid!
The
Amino
Acids
Condensation and Hydrolysis
Condensation: joins amino acids into a dipeptide or
polypeptide, produces water
Hydrolysis: breaks a polypeptide into amino acids, uses
water
Peptide bonds
Although “peptide bond” refers specifically
to the bond C-N bond formed between
two amino acids, it refers to a larger
structure:
Be able to draw two
amino acids forming
a peptide bond!
The dark grey bond
is the peptide bond,
but the entire pink
area is needed .
Primary structure
Number (can be ~50–1000)
and order of amino acids in a
chain (polypeptide) held together
by peptide bonds
Each polypeptide is coded for by
a gene (in the DNA).
Enormous range of possibilities!
(20n, n=# of amino acids)
Type / location of amino acids
used relate to the protein’s
function
Secondary structure
Held together by hydrogen bonds
Regular and repeating, formed by N-C-C
backbone
Two main forms
-helix (myosin, hair)
-pleated sheet (silk)
Tertiary structure
Final 3-dimensional
folded shape of
polypeptide
R-groups mostly
determine bonding;
may include:
ionic bonds
Hydrogen bonds
covalent (disulfide)
bonds
hydrophobic
interactions
Quaternary structure
(Only in some proteins) 2+ polypeptide chains held
together by all types of bonds, primarily through Rgroups
Conjugated proteins also include elements and
structures called prosthetic groups that are not amino
acids (part of quaternary structure)
Protein Structure
Review
Primary - order of
amino acids
Secondary - H-bonds in
backbone
Tertiary - 3D shape
from R-groups
SOMETIMES
Quaternary - 2+
polypeptides and
prosthetic groups
What levels can you find?
Explore the biotopics jsmol library. You should
compare and contrast: glucagon, myogloblin, and
hemoglobin.
Functions of proteins
Structure and support - microtubules influence cell
shape, collagen in skin, spider silk in webs
Transport - hemoglobin carries oxygen, microtubules
serve as highways in cells
Movement - actin and myosin make muscle fibers
Communication - hormones, ex. insulin
Defense – immunoglobin antibodies, lysozyme in tears
Response – response, eg. rhodopsin in eyes
Enzymatic reactions - speed up reactions, eg.
Digestion of food, building cell parts, Rubisco in
photosynthesis
Energy storage - ~4 Cal/gram (not considered a
primary function)
Final Protein shapes: Fibrous
Fibrous - long, thin, insoluble in water
Collagen: STRUCTURE in skin, tendons
Actin and myosin: muscle fibers allow
MOVEMENT
Final protein shapes: Globular
Globular - rounded, bulky, mostly
soluble in water
Hemoglobin: TRANSPORT oxygen in red
blood cells
Immunoglobin: antibody DEFENSE against
foreign substances
Significance of amino acid variety
The different R-groups allow a variety of shapes
The active sites of enzymes have the correct
polarity and/or charge to attract the substrates
Non-polar amino acids can be anchored in
non-polar membranes
A membrane channel protein can have nonpolar R-groups on the outside and polar Rgroups on the inside, creating a hydrophilic
passageway through the membrane
Final Protein Shape Depends on
Environment
A protein that has lost its function (usually
permanent) is “denatured”
Excessive heat (not cold) or unsuitable pH
(acidic or alkaline) can disrupt bonding and
denature the protein
Look at the
production of
“century eggs”
(ไข่ เยีย่ วม้ า) – using pH
to denature!
Genes and Proteins
DNA is for information storage only, while proteins
have a huge variety of functions.
Each individual of a species has a slightly different set
of DNA (genome).
Each gene in the DNA codes for a protein
Almost all species have the same code for translating from
DNA to protein sequence!
Each individual has a unique proteome, influenced
primarily by DNA but also by environment (stimuli like
stress can turn genes on or off).
Discuss the connections between stem cell
differentiation and proteomes.
Map of C. elegans
(nematode worm) proteins
and their interactions
Lesson 2:
Enzymes
Enzymes
 Made of protein
 Globular
 Catalyze ONE (or very few) specific reactions
 Speed up rate of reaction
 Lower the activation energy of a reaction
 Very specific to substrate molecule(s)
Activation Energy (Ea)
Collision Theory
In liquids (like cytoplasm) molecules are moving around,
knocking into each other (colliding)
When some molecules strike at the right orientation, with
enough energy they will react (split apart, combine, shift
bonds, etc)
The rate of reaction without an enzyme can be noticeable, or it
can be so rare that it’s basically never.
Enzyme structure
 The active site is where the
substrate binds (other
molecules bounce off)
 The enzyme is like a lock,
and the substrate(s) are like
the key(s) that fits it
Enzymes and Collision Theory
Enzymes capture substrate(s) that collide with
the active site and hold them at an angle that
places stress on existing bonds and aligns
substrates (if more than one)
This increases the rate of reaction, often by
millions of times.

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Temperature = increased energy
 increased collisions 
increased rate, BUT increased
too much will break bonds,
denature the structure
pH = [H+] affects bonding,
attracting or repulsing R-groups,
can denature the protein
[Substrate] = at low levels more
substrate increases rate of
reaction because more collision,
at high levels no effect because
enzymes already saturated
Rate of reaction is also affected
by [Enzyme] = a higher
concentration will lead to more
collisions, therefore more
reactions
Which factors affect
enzyme activity?
[ ] means concentration
Factors Affecting Enzyme Function
Temperature
pH
[Substrate]
[Enzyme] 
Be able to draw these graphs and
discuss what is happening at each part!
Enzymes are evolved to work
in their environments
Eg. All enzymes can be denatured by a
pH that is unsuitable, but which pH is
optimal (best) depends on the enzyme
Using animations to collect data
We will use this animation for modeling
enzyme activity.
Inhibition of Enzymes
Competitive



Substrate and inhibitor
both bind to active site
Inhibitor and substrate are
often chemically related
Inhibitor physically blocks
substrate
Non-competitive
 Substrate binds to active
site, inhibitor binds to
allosteric site
 Inhibitor and substrate
not chemically similar
 Inhibitor changes the
shape of the enzyme and
active site
Inhibition of Enzymes, cont.
Competitive
Non-competitive
In which case would the [substrate] affect the
rate of reaction?
Answer: Competitive; more substrate molecules will more
successfully for the active site against the inhibitor
Competitive
inhibition
• Ethanol is the alcohol found in drinks
• Ethanol is converted to acetaldehyde
• Aldehyde dehydrogenase immediately
converts acetaldehyde to acetate so it
never builds up
•Further enzymes modify acetate for
energy release or energy storage
• Disulfiram binds to the active site of
aldehyde dehydrogenase, so
acetaldehyde builds up causing nausea
and discomfort
• Used as a pill to treat alcoholism
Non-competitive inhibition
 Lead replaces zinc at an
allosteric site in aminolevulinic
acid dehydratase (ALAD), an
enzyme that helps produce
hemoglobin
 Changes shape of active site
so ALAD does not function,
leading to anemia
 Lead inhibits many enzymes leading to
many other symptoms including
headache, insomnia, insanity, death
Compare the three conditions.
Why do both types of inhibition have an increased rate of reaction at
low levels of [substrate]? Why does non-competitive inhibition show
no effect from [substrate] at higher levels?
Metabolic pathways
 Many reactions are actually a series of
steps, each catalyzed by a different
enzyme, in a chain or cycle
End-product inhibition -Negative feedback
 Helps maintain balance (homeostasis) by
preventing overproduction
 The final product serves as an allosteric
inhibitor for an enzyme early in the pathway
End-product inhibition in threonine
 isoleucine pathway
Isoleucine is an allosteric
inhibitor of threonine
deaminase, the first
enzyme in the metabolic
pathway that converts
threonine to isoleucine.
Discuss the role(s) of:
• Threonine
• Threonine deaminase
• Isoleucine
What happens when levels
of isoleucine are low? High?
Use of lactase enzyme in
lactose-free milk production





Specific yeast is cultured to harvest
its lactase
Lactase breaks lactose
disaccharide into glucose and
galactose
People who lack this enzyme are
lactose-intolerant
May have diarrhea, gas, and
intestinal pain when eating dairy
products
Lactase can be added to produce
lactose-free dairy foods
Lactose Free Milk
Methods
Add lactase directly to
milk
Immobilize lactase on a
screen and slowly pour
milk over (no lactase in
final product)
Non-enzyme method
Ultrafiltration
Advantages
Sweeter taste
Digestible by lactoseintolerant people
Fewer allergies
If made into ice cream,
less gritty
If made into yogurt,
process is faster
Uses of immobilized enzymes
Removal of wastes from contaminated
water
Pectinase and cellulase to release juice
Antibiotic production
Much more! 
Using Databases to look for
Anti-Malarial Drug Targets
Developing medicines is extremely expensive and
time consuming
Databases and pool knowledge and lab results
Allows selection of most useful enzymes to target, or
drugs that are known to be tolerated in humans
Efficient and more rapid development
Read this abstract. What did the authors do?
Explore the research database site TDRtargets.org. What
makes a gene a good target?
Links allow further exploration, including amino acid
sequencing (see BRENDA)
Optional Challenge Activity!
Are you a gamer?
Want a real challenge?
Want to make a difference?
Try Foldit!
Learn how amino acids interact
Like a crazy-hard puzzle 
Read an article here:
Gamers took 3 weeks to solve a protein
researchers had worked on for 10 years!
Can be used by HS students – see how far
you can go!!
Lesson 3:
Nucleic Acids
Nucleic Acid Structure
Nucleic acids are chains of
covalently-bonded nucleotides
Nucleotides are the monomers
(building blocks) of nucleic
acids
Each nucleotide has thee parts.
Nucleotide:
Sugar (ribose /
deoxyribose)
Phosphate
Nitrogen Base
Nucleic Acid Functions
Nucleic acids polymers include:
DNA: stores genetic information
RNA: relays relevant information from
DNA to the rest of the cell; directs the
production of proteins
One nucleotide (monomer):
ATP: the energy currency used in cells
The Nitrogenous Bases
Purines – two rings, the same in DNA and RNA
Adenine
Guanine
Pyrimidines – one ring
Cytosine
Thymine (in DNA)
Uracil (in RNA)
Nucleotides form
Nucleic Acids
Energy is released from
nucleoside triphosphates; two
phosphates break away.
The phosphate of one
nucleotide links to the 3rd
carbon in the sugar of another
Creates a covalently bonded
phosphate – sugar backbone
The DNA Double Helix
Nitrogen bases form specific (complementary) pairs
Adenine pairs with Thymine (A – T)
Guanine pairs with Cytosine (G – C)
Notice that a purine always pairs with a pyrimidine
Each complementary base pair forms hydrogen bonds
A-T form 2 hydrogen bonds
G-C form 3 hydrogen bonds
DNA Double helix
Antiparallel strands:
in order for the
nitrogen bases to form
hydrogen bonds, the
two DNA strands
must be facing
opposite directions
Constant width:
Because a small
pyrimidine always
bonds with a larger
purine, the two strands
are always the same
distance apart
DNA double helix
The sugar-phosphate backbones are
on the outside of the helix
The nitrogen bases form the flat
inner rungs (steps on the ladder) of
DNA
If you know the order of Nitrogen bases on
one strand of DNA, you can determine the
other:
Practice: ACTTGCCA
Answer: TGAACGGT
DNA packaging in Eukaryotes
In eukaryotes and archaea (NOT eubacteria)
DNA is organized into nucleosomes:
8 histone proteins, 2 loops of DNA, one histone “tie”
DNA
to Chromosomes
• DNA must be uncoiled
for the information to be
“read” (transcribed)
• DNA must be supercoiled
when not in use or it will
tangle and tear
•Histone proteins organize
the DNA by winding it up
RNA types
mRNA (messenger)
Carries a copy information from
individual genes to ribosomes (as
needed)
rRNA (ribosomal)
Acts as a catalyst (enzyme, except
not protein) joining amino acids into
a polypeptide.
tRNA (transfer)
Translates from nucleotide code to
assemble correct amino acid
sequence
RNA v. DNA
Nucleic
acid
polymer
# of
strands
Nitrogenous
bases
DNA
2,
double
helix
Thymine,
Adenine,
Guanine,
Cytosine
Deoxyribose
Genetics,
information
storage
RNA
1,
not a
helix
Uracil,
Adenine,
Guanine,
Cytosine
Ribose
Information
transfer (DNA
to protein),
protein
synthesis
Pentose sugar
Function
Hershey-Chase Experiment, 1952
For a long time, protein
was considered most
likely to be the genetic
material
Complex enough to store
large amounts of
information
In the 1940s, evidence
started to accumulate
that DNA might be the
genetic material
Led to many researchers
racing to determine the
structure!
Hershey-Chase showed that
that bacteriophage viral
proteins do not infect bacteria
cells, but viral DNA does!
Hershey Chase –
experimental procedure
The Structure of DNA:
The Great Race!
Caltech
Cambridge
King’s College
Linus Pauling
James Watson &
Francis Crick
Rosalind Franklin /
Maurice Wilkins
Three teams:
Franklin (and Wilkins):
X-ray crystallography
Photo 51: Go through
this interactive.
Know at least that:
•The “X” suggests a
helix
•The 4 white
“diamonds” suggest a
repeating helix
•The “missing band” in
the X suggests a
double helix
Watson and Crick models
• Like an early type of
“foldit” using
cardboard cutouts of
the different pieces
• Made to accurately
represent bond length
and atomic location
• Relies on modeler’s
understanding of how
elements would
interact
• Published paper 1953