Download Answers for possible questions about the new material HbS·(O2)4 (aq)

Answers for possible questions about the new material
$1. Draw a generalized structure for an amino acid (use may use “R” for the side chain”).
H
H
amino
group
carboxyl
group
O
N
C
C
H
O
H
+
H
H
N
C
H
R
H
R
R represents the side chain
O
C
O
-
Predominant structure at neutral pH
$2. Show how two amino acids join to form a peptide bond.
$3. Why would it be very appropriate for the amino acid, aspartic acid, to lie on the outer surface of a cytoplasmic
protein?
A cytoplasmic protein is surrounded by water which is polar. Aspartic acid’s side chain is polar
and negatively charged at neutral pH. It is hydrophilic.
$4. Draw a reaction coordinate diagram for the hydrolysis of a dipeptide (like Gly-Ala). Then draw another line on
the same diagram to describe the reaction when catalyzed by an efficient catalyst.
transition state
uncatalyzed reaction
Eact uncatalyzed
gly-ala + water
catalyzed reaction
G
Eact catalyzed
∆G is negative
gly + ala
Reaction Progress
The G values on my diagram should be Go.
The graph was getting crowded so I didn’t include the transition state for the catalyzed reaction,
although it should be indicated.
$5. Describe the molecular basis of sickle cell anemia, one treatment, and indicate why the trait is found at
relatively high levels in some populations.
Normal human Hb has glutamic acid (Glu) at position 6 of its beta chain. A mutation in the DNA results
in the conversion of GAG (in the RNA) to GUG (in the RNA) in sickle cell hemoglobin (HbS). GUG is
the codon for valine (Val). The valine side chain is much less polar than that of Glu. When HbS is in its
low affinity form (deoxygenated), HbS starts to polymerize into long chains that protect the valine side
chain from water and precipitate (come out of solution to form a solid).
HbS·(O2)4 (aq)
HbS(s) + 4 O2(aq)
The long rods that form lead to a change in shape and loss of flexibility of the red blood cells. This in turn
leads to restricted blood flow in the capillaries and rupturing of red blood cell membranes. Ultimately this
causes the broader problems associated with sickle-cell crises (pain, liver problems, etc.).
One of the treatments for sickle-cell disease is hydroxyurea. This drug works by inducing the synthe sis
of the fetally produced gamma (γ ) chain, that can partially replace the beta (β) chain. This reduces the
incidence of a sickle-cell crisis.
Sickle-cell heterozygotes (individuals who have one wild type (wt) and one sickle cell Hb gene) are
resistant to malaria. This resistance may account for the relatively high frequency of the sickle cell trait in
individuals from areas where malaria is prevalent.
$6. Provide a chemical explanation for the graph shown at
pH vs. Activity
left that shows the pH dependence of activity of an enzyme.
Your answer must contain an equation for a chemical
reaction.
3.50E-07
The enzyme activity is highest in a range of ~pH 2 to 4.
As the pH becomes more basic, from ~pH 4 to ~pH 8,
the activity steadily decreases. Above pH 8, the
activity is close to zero.
Consider the active enzyme as a weak acid. As the pH
increases, the enzyme gives up its H+ and forms the
inactive conjugate base.
H-Enzyme + OH Enzyme + H2O
(active)
(inactive)
Enzyme activity
3.00E-07
2.50E-07
2.00E-07
1.50E-07
1.00E-07
5.00E-08
0.00E+00
2
4
6
8
pH
$7. What is the “Central Dogma of Molecular Biology?”
It shows the direction and
flow of information.
DNA
transcription
RNA
translation
Protein
reverse
transcription
replication
$8. What amino acid sequence would be coded from the mRNA template shown below? Make sure that you
indicate the polarity of the peptide.
Stop
5'
AUG GAC CCG UGC GUC GUU UCU GUG ACA UGA CAAC 3’
(N- terminus) Met -Asp- Pro - Cys – Val – Val – Ser – Val – Thr (C- terminus)
$9. Describe the two conformations of hemoglobin and describe how they aid in transport of oxygen to your
tissues.
Hemoglobin (Hb) has two conformations: a form with a high affinity for oxygen (the main Hb form in the
lungs) and a form with low affinity for oxygen (the main Hb form present in the extremities and at lower
pH). Hb shifts back and forth between these two forms as it circulates thru the body.
In the lungs, after one O2 molecule binds to a Hb subunit, the affinity of the other three subunits for O2
increases. As each subunit binds O2, the attraction grows stronger (a cooperative effect), so in the lungs
where O2 concentration is high, all of the subunits are bound to O2, meaning Hb can pick up the maximum
load of O2.
In the extremities, O2 concentration is low. As the first subunit releases O2, the affinity for O2 by the
other subunits decreases. This allows the other subunits to more easily release O2. So in the tissue where
O2 concentration is lowest and where O2 is needed most, the Hb molecule is able to deliver the maximum
amount of oxygen.
10
$10. Why is it important that DNA be able to replicate itself millions of times without error? What feature of DNA
structure is particularly important with regard to avoiding errors?
DNA needs to be able to replicate itself without errors, because an error if not corrected results in a
mutation. Mutations are rarely positive for the cell or organism, sometimes neutral and often have
negative consequences. Mutations can result in the formation of ineffective proteins, can cause disease
states, and cancer.
The structural feature of DNA that helps avoid mutations is that DNA is double stranded with
complementary bases. This means that (1) each strand contains the information in each sequence, and (2)
copying errors can be detected early on as a mismatch that can be recognized and repaired before
replication.
$11. Give one sentence descriptions of the roles of mRNA, tRNA, and rRNA in the cell.
mRNA, tRNA, and rRNA are three major classes of RNA in the cell.
Messenger RNA (mRNA) carries genetic information from DNA, located in the nucleus in eukaryotic
cells, into the cytoplasm where the information can be translated into protein.
Transfer RNA (tRNA) is the direct interpreter of genetic information found in mRNA into the sequence
of amino acids for a protein using its three base anti-codon located at one end and attached amino acid at
the other.
Ribosomal RNA (rRNA) is the RNA component of ribosomes and it is involved in the catalysis of linking
one amino acid to the next.
$12. What are the levels of structure of proteins? What kinds of forces/bonds maintain this structure?
Primary (1o) structure of proteins is the amino acid sequence. It is maintained by covalent bonds
called peptide bonds.
Secondary (2o) structure is a regular repeating structure due to folding of the polypeptide chain.
The main types are alpha-helix and beta sheet (either parallel or anti-parallel). Secondary structure is
maintained by hydrogen bonds formed between a hydrogen (donor) attached to the nitrogen in the
backbone of the chain and the non-bonding pair on the carbonyl oxygen (C=O) in the backbone.
Tertiary (3o) structure refers to the location of each atom of the protein relative to every other
atom in three dimensional space. This structure is maintained by hydrophobic interactions, hydrogen
bonding, covalent (disulfide, -S-S-) bonds, ionic bonds and London forces.
Quaternary (4o) structure exists only for proteins that have more than one chain or subunit. It
describes the way the subunits are arranged and bind to each other. It is maintained by the same forces as
tertiary structure.
$13. Describe where DNA is located and where proteins are synthesized. What molecules and processes exist that
allow the transfer of this information from one location to the other?
DNA is located in the nucleus. Proteins are synthesized on ribosomes in the cytoplasm. The information
encoded in the DNA is carried from the nucleus to the cytoplasm via messenger RNA (mRNA). mRNA
is transcribed from DNA and processed in the nucleus and then passes thru the nuclear membrane into the
cytoplasm and moves to the ribosomal machinery where it is translated to protein. The translation
process uses tRNA’s that have (1) an anti-codon on one end that can “read” an mRNA codon and (2) its
designated amino acid on the other end.
$14. Draw a DNA molecule being replicated. Include the direction the DNA is unwinding, the polarity of the
parent and daughter strands and the direction the daughter strands are being synthesized.
leading strand
3'
5'
parental strands
daughter strands
5'
3'
5'
3'
lagging strand
3'
5'
direction of unwinding and of replication
$15. Given an organic molecule, be able to circle the chiral carbons.
Example with chiral carbons circled:
Br
H
H
H
H
C
C
C
C
Cl
Br
H
O
$16. What is a mutation? Be familiar with different types of mutations.
A mutation is a change in the DNA that doesn’t get repaired. Once a base change mutation is replicated,
it is fixed as a mutation.
One type of mutation is a point or single base change. It can be neutral (resulting in a codon change for
the same amino acid), a conservative change (resulting in a codon change for an amino acid whose side
chain has similar polarity or charge), or non-conservative mutation (resulting in an amino acid whose side
chain has very different polarity or charge). A point mutation could even result in a nonsense mutation,
which is when a codon gets changed to one of the stop codons.)
Other types of mutations that you should be familiar with include deletions, insertions and frameshift
mutations.
$17. You are attending a family reunion, and the subject of mitochondrial DNA comes up (as it often will at such
gatherings). How likely is it that you have the same mtDNA sequence as your cousin Luke? Luke is your mother’s
sister’s son. Briefly explain your logic.
100% likely. Mitochondrial DNA is inherited maternally in humans. Therefore both your mother
and her sister inherited their mtDNA from their mother, and (barring mutation) both you and
Luke will inherit that same mtDNA.
hydrogen bonding
3'
A
T
O
sugar
sugar
5'
O
PO4
PO4
O
G
sugar
sugar
C
O
PO4
PO4
T
A
O
sugar
sugar
O
PO4
PO4
3'
G
C
O
sugar
sugar
$18. Draw a cartoon model of DNA indicating how the three major pieces are
connected. Indicate the location of hydrogen bonds.
O
5'
$19. Given the following DNA sequence, what would the complementary RNA sequence be? Indicate the polarity
of the RNA.
ATGGACGTGCGTAA
3’ U A C C U G C A C G C A U U
5'
3’
5’
$20. What is the definition of lipids. What is a generalized structure of a fatty acid, of a triglyceride?
Lipids are biological compounds that are soluble in non-polar solvents.
A fatty acid consists of a carboxylic acid, “the head”, and a long, non-polar, carbon chain, “the tail”.
O
CH 3 -CH 2-CH 2 -CH 2 -CH 2 -CH 2 -CH 2 -CH 2-CH 2 -CH 2 -CH 2 -CH 2 -CH 2-CH 2 -CH 2 -C
O
H
head
tail
A triglyceride consists of three long chained fatty acid molecules linked by a ester
linkage to glycerol.
fatty
acid
Glycerol
fatty
acid
fatty
acid
$21. In general, how and why does unsaturation affect the melting points of fatty acids.
Fatty acids have long carbon chains that are non-polar. The intermolecular forces involved are
mainly London forces that depend on the molecules in question to lay close to each other. Unsaturated
chains are fairly straight and are able to line up close to each other. The cis double bonded carbons in
unsaturated molecules put a bend or kink in the chain. This reduces prevents the chains from lining up
close to each other, reducing the London forces between the molecules. With reduced IMF, it takes less
heat to melt unsaturated chains reducing the melting point.
saturated
unsaturated
22. Describe in words and with a picture, the fluid mosaic model of membrane structure. (This question will not be
on the final.)