exam 1 answers

What is an allosteric effector? How do such molecules stabilize and/or destabilize the conformation of hemoglobin during oxygen transport? Discuss with examples. How does the pH influence this process?

Allosteric modulators or allosteric effectors refer to specific molecules that bind a protein and modulate the protein activity. They bind to allosteric (Allo=other, steric=site or structure) sites or sites other than the substrate binding sites. They bind reversibly to these allosteric sites which are separate from substrate binding or active site. Modulation of activity occurs through change in protein conformation. 2, 3 bisphosphoglycerate (BPG), CO2 and protons are allosteric effectors of Hb which influence the binding of O2 Regulation of Hb oxygen binding by hydrogen ions and carbon dioxide is called Bohr effect. Increased CO2 leads to decreased pH At decreased pH several key AA's protonated, which help in forming a salt bridge to stabilize T state or low affinity state. Similarly, the HCO3- combines with N-terminal α-amino group to form carbamate group to stabilize T-conformation. Carbamate ion. Stabilization of T-state leads to oxygen release. At higher pH the same AA's are deprotonated, breaking the salt bridges, leading to destabilization of T-state.

What proteins exhibit mostly secondary structure and what proteins exhibit tertiary structures? Give one example each with the type of secondary structure it contains.

Fibrous proteins contain secondary structure, they have alpha helix. e.g. keratin Globular proteins contain tertiary structure. e.g. myoglobin

What kind of biochemical unity you find in the diverse biological world? Provide specific examples for each feature.

From chemical perspective, life has three basic characteristics- complexity, ability to extract and transform energy for their growth, and maintaining identity with a capability for variation. Biological world is diverse, yet they have biochemical unity. A few building blocks can be combined in different ways to produce a wide variety of large structures. For example: Same set of 20 amino acids are used in synthesizing a variety of proteins in all living beings. Biological activities require energy. Interconversion of energy require large biochemical machines, yet functions depend on simple chemical processes such as protonation and deprotonation and interactions. Identical chemical reactions, and pathways involving dehydration/condensation and hydrolysis are involved in synthesis and degradation of biomolecules. For example, ATP is the universal energy currency of cell in all living systems powering various chemical reactions. Nucleic acids are used as genetic material in all life forms, where they not only determine their identity but also provide the basis for variation.

Why is hemoglobin an efficient transporter compared to myoglobin to carry oxygen from lungs to tissues? What could be the use of myoglobin in a vertebrate and how?

Myoglobin (Mb) has hyperbolic O2 binding curve, Mb binds O2 tightly and releases O2 at a very low pO2.which is much lower than the prevailing partial pressure. However, it could serve storage function Hemoglobin (Hb) has sigmoidal O2 binding curve, Hb high affinity for O2 at high pO2 (lungs) and low affinity for O2 at low pO2 (tissues). Binding at one site within tetramer of Hb increases the likelihood that oxygen binds at the remaining unoccupied sites. Unloading of oxygen at one heme facilitates unloading of oxygen at others. This sort of binding behavior is called cooperative, because binding reactions are not independent of one another. Myoglobin serves as oxygen storage protein where oxygen can be released at extremely lower concentrations.

"Amino acids used in making a polypeptide have an amino group and carboxyl group, and these groups can be present on any carbon atoms." Is that a correct statement? Why so? What is the basis for classification of amino acids to non-polar (but not aromatic), polar, and two oppositely charged (at physiological pH) amino acids? Provide examples with their exact name, three letter and single letter codes.

No, it is not correct. The amino acids found in polypeptides are α-amino acids where the carboxyl group and amino group are attached on the same carbon which is an α-carbon but not at different positions in the carbon skeleton. For example, the given structure, β-alanine, where amino group is on β-carbon (H3N+-CH2-CH2-COO-) is not part of polypeptide, only α-alanine (H3C-CH(NH3+)-COOH) is part of polypeptide. Any nonpolar amino acid, polar, acidic and basic amino acid depends on the presence of side chain with aliphatic carbon tail or polar groups or ionizable groups. Non polar: Alanine or ala or A Polar: serine or Ser or S Acidic: Aspartate or Asp or D with ionized carboxylate side chain Basic: Lysine or Lys or K with protonated amino group in the side chain

Why is the ordered native conformation of a protein stable while the general tendency of system/universe is to increase the disorder or randomness? Discuss your interpretation in terms of the reasons behind the various protein folding diseases/disorders.

Protein folding is achieved by hydrophobic effect, which increases entropy by freeing water (favorable), other non-covalent interactions provide favorable (decrease of) enthalpy value, and all of these work in a highly cooperative process. The only factor that opposes the stabilization of native conformation is Conformational entropy which decreases the entropy (unfavorable to folding) of the sequence. However, the net value of Gibbs free energy change for these unfavorable and favorable interactions results in small but significant with a negative sign or in other words it yields lowest energy conformation. Since the resulting structure has low energy, the native conformation is stable. Since the net Gibbs free energy change is small, any interference in those folding events can lead to protein misfolding which lead to disorders and diseases Change in primary structure can lead to change in shape of protein. E.g. Glu4Val in β-globin Protein misfolding leads to amyloidogenic insoluble fibers in prions or Alzheimer or Parkinson disease.

Why do you think water is essential for life? Explain in terms of the effect/s we learned in the class on the properties of biomolecules we had studied, so far, in the class. Why do you think such effect/s predominate with water?

Water is essential for maintaining structure and function of biomolecules. Water acts as medium and can act as base or acid. It is the medium that facilitates various reactions and interactions of life processes. When hydrophobic substances are added to water, normal H-bonding is disrupted as water molecules are constrained to avoid contact with non-polar molecules, thus leading to loss of entropy in the system. So non-polar molecules tend to clump together removing contacts with aqueous phase (water), this is referred to as hydrophobic effect. Hydrophobic effect require the presence of water. It is required for attaining specific structure. Biomolecules such as proteins contain both hydrophobic and hydrophilic groups that lead to specific arrangement of the constituent groups that minimize the unfavorable interactions and maximize the favorable interactions, so that the overall entropy is increased. In this effect entropy predominate over enthalpy due to the sheer number of solvent water molecules (55.5X6.023X10^23 per L).

Which of the following statements about amino acids is TRUE? Choose the most appropriate option. a. All of the answers are correct. b. Amino acids are dipolar ions, or zwitterions. c. Amino acids contain a central α-carbon. d. All amino acids exhibit alternate cis and trans arrangement of their side chains in a polypeptide. e. Amino acids contain a central α-carbon and are also dipolar ions, or zwitterions.

a. All of the answers are correct.

Which of the following statements regarding an amino acid with an ionizable side chain is TRUE? a. For aspartate, if the α-carboxyl group is protonated, then the side chain is also protonated. b. For glutamic acid, if the side chain is protonated, then the α-carboxyl group must also be protonated. c. None of the answers is correct. d. All amino acids with ionizable side chains have charged groups at physiological pH. e. The pKa of the side chain is always lower than the pKa of the carboxyl group.

a. For aspartate, if the α-carboxyl group is protonated, then the side chain is also protonated.

Which of the following statements is true for BOTH an α helix and a β-pleated sheet? a. Formation is driven by hydrogen bonds between main-chain C=O and NH groups. b. It is shaped like a rod. c. It cannot form in the presence of the reducing agent β-mercaptoethanol. d. Formation is driven by hydrogen bonds between amino acid side chains e. It is a type of primary structure.

a. Formation is driven by hydrogen bonds between main-chain C=O

Which statement about living systems is NOT true? a. Living systems are in equilibrium with their surroundings. b. Living systems have efficient mechanisms to convert chemical energy from one form into another c. Living systems can transmit information. d. Living systems maintain a more-or-less constant composition. e. Living organisms can be described as an open system.

a. Living systems are in equilibrium with their surroundings.

An increase in disorder: a. leads to positive ΔS in the factor TΔS b. is found in every exergonic reaction c. is required for a process to be non-spontaneous d. results in a decrease in entropy e. is characteristic of a system with an altered enthalpy

a. leads to positive ΔS in the factor TΔS

Formation of disulfide bonds in a tertiary structure of a polypeptide require: a. overall folding mediated by hydrophobic effect and oxidation b. secondary structure and oxidation c. overall folding mediated by hydrophobic effect and reduction d. charged amino acid residues e. isomerases

a. overall folding mediated by hydrophobic effect and oxidation

The conversion of hemoglobin from the T to the R form involves breaking C-terminal a. salt bridges b. Covalent bonds c. Tertiary structure d. symmetry e. decrease.

a. salt bridges

_____ is an aromatic amino acid whose side chain can participate in ______ when it is part of polypeptide, and can get charged at extremely high pH (>11) a. tyrosine; hydrogen bonding b. proline; α-carbon; carbonyl oxygen c. proline; carbonyl oxygen d. phenylalanine; nitrogen; e. proline; nitrogen;

a. tyrosine; hydrogen bonding

Which of the following statements is TRUE? a. α-keratin, the main protein in hair, contains both α helices and β sheets. b. None of the answers is correct. c. α-keratin is classified as a globular protein d. Myoglobin, a globular protein, contains both αhelices and a few β strands. e. Hemoglobin contains both primary and tertiary structure but not quaternary structure.

b. None of the answers is correct.

Sickle cell hemoglobin is a result of: a. low oxygen levels b. Substitution of acidic amino acid with nonpolar amino acid c. Low globin content d. Lack of cooperativity e. Replacement of hydrophobic amino acid

b. Substitution of acidic amino acid with nonpolar amino acid

The blood buffering system is based on: a. the decrease of the blood pH due to the production of H+ the reaction of CO2 with H2O to form carbonic acid b. all of the given features play a role. c. the ionization of aqueous carbonic acid to H+ and the bicarbonate anion d. the excretion of bicarbonate and ammonium from the kidneys

b. all of the given features play a role.

Which bonding interactions are NOT considered to be "weak" in proteins? a. van der Waals forces b. bond formed by condensation c. hydrophobic interactions d. hydrogen bonds e. ionic bonds

b. bond formed by condensation

Salts are soluble in water because a. low dielectric constant of water keeps the charged species apart thereby increasing entropy b. dielectric constant of water keeps the charged species apart thereby increasing entropy c. dielectric constant of water keeps the charged species together thereby increasing entropy d. hydrogen bonding with salt species e.None of the given options applicable

b. dielectric constant of water keeps the charged species apart thereby increasing entropy

The first step in the folding of disordered polypeptide chains into stable proteins is the formation of: a. β-bulges b. secondary structural elements c. multi-strand aggregates d. disulfide crosslinks e. primary structural elements

b. secondary structural elements

At pH 1, arginine (pKas are α-carboxylate 1.82, α-amino 8.99, guanidino 12.48) would be charged as follows: a. +1 α-carboxylate, -1 α-amino, -1 guanidino, -1 net charge b. 0 α-carboxylate, 0 α-amino, +1 guanidino, +1 net charge c. 0 α-carboxylate, + 1 α-amino, +1 guanidino, +2 net charge d. -1 α-carboxylate, + 1 α-amino, +1 guanidino, +1 net charge e. +1 α-carboxylate, 0 α-amino, -1 guanidino, 0 net charge

c. 0 α-carboxylate, + 1 α-amino, +1 guanidino, +2 net charge

What percentage of myoglobin is bound with its ligand when the oxygen concentration in the surroundings is around 12 torr, where half of the protein is bound with oxygen at 2.8 torr? a. 78% b. 50% c. 81% d. 100% e. 64%

c. 81%

Protein misfolding can be triggered by: a. cleavage of a portion of secondary structure b. Alteration of tertiary structure c. Either of the listed causes can cause misfolding. d. Change in pH e. Conversion of α-helix to β-strands

c. Either of the listed causes can cause misfolding.

Reaction 1 has a ΔG° of -45.3 kJ/mol, and Reaction 2 has a Δ G° of -11.4 kJ/mol. Which statement is TRUE of these two reactions? a. Reaction 2 will not occur at all b. Both reactions occur at the same speed c. It is impossible to know which reaction occurs faster with this information d. Reaction 2 occurs faster. e. Reaction 1 occurs faster.

c. It is impossible to know which reaction occurs faster with this information

A common feature of all biomolecules is: a. Ability to catalyze reaction b. Their ability to carry genetic information c. To form and degrade by dehydration and hydrolysis, respectively d. To transform energy from one form to another e. Their capacity to form bilayer

c. To form and degrade by dehydration and hydrolysis, respectively

The protein domain is: a. mediated by disulfide bond b. requires overall folding of peptide c. an independently folding unit d. a motif e. cannot be moved from one protein to another

c. an independently folding unit

Hydrophobic interactions between nonpolar molecules or groups: a. are the result of strong attractions between nonpolar regions. b. are the result of strong interactions between water and nonpolar regions. c. decrease the order of water molecules d. depend on strong permanent dipoles in the nonpolar molecules. e. result from the tendency to maximize water's contact with nonpolar molecules.

c. decrease the order of water molecules

In the peptide Lys-Pro-Gly-His-Asp-Arg, the net charge is ______ at physiological pH 7.3. a. four, positive b. fully protonated c. one, positive d. two, negative e. zero

c. one, positive

Myoglobin and the subunits of hemoglobin have: a. very similar primary and tertiary structures. b. very similar primary structures, but different tertiary structures. c. very similar tertiary structures, but different primary structures d. no obvious structural relationship. e. very different primary and tertiary structures.

c. very similar tertiary structures, but different primary structures

Which of the following statements does not apply to the Kd value in the equation for the oxygen binding curve of myoglobin? a. It is numerically equal to p50. b. It is the value of pO2 at which Y = 0.5. c. It is a measure of the affinity of myoglobin for oxygen. d. If Y < Kd, then myoglobin is more than 50% saturated with oxygen. e. It is defined as that oxygen partial pressure at which half of the oxygen binding sites are occupied.

d. If Y < Kd, then myoglobin is more than 50% saturated with oxygen.

The coordinated nitrogen atoms in the heme prosthetic group have _____ character, which prevents conversion of the heme iron to the _____ state from the _____ state a. electron-accepting; Fe2+; Fe3+ b. electron-donating; Fe2+; Fe3+ c. electron-accepting; Fe+; Fe0 d. electron-donating; Fe3+; Fe2+ e. electron-accepting; Fe3+; Fe2+

d. electron-donating; Fe3+; Fe2+

Which of the following increases the affinity of hemoglobin for oxygen: a. the formation of N-terminal carbamates. b. increased salt bridges c. all of the given features can be applicable d. increasing pH. e. an increase in 2,3 bisphosphoglycerate concentration.

d. increasing pH.

Stabilization of T state is facilitated by: a. oxygen delivery b. for maintenance of high affinity state c. All of the features may be applicable d. low oxygen, high proton content e. for carbon dioxide binding f. oxygen binding and protons

d. low oxygen, high proton content

A bicarbonate buffer of pH 6.1 needs to be prepared. What would you add to 500 mL of 0.4 M sodium carbonate solution in order to make this buffer? (Hint: carbonic acid has two pKa values, 6.1 and 10.3) a. cannot be determined with given information b. 0.5 moles of base c. 0.4 moles of diprotic acid d. 0.3 moles of diprotic acid e. 0.3 moles of monoprotic acid

e. 0.3 moles of monoprotic acid

You have a mixture of proteins with the following overall pKa values. Which of the statements below is TRUE? Protein X pKa = 2Protein Y pKa = 6Protein Z pKa = 7 a. At a pH of 8, protein Y will be more protonated than protein Z. b. All of the answers are correct. c. At a pH of 4, protein Y will be more deprotonated than protein X. d. At a pH of 6, the solution of protein X will contain more hydrogen ions than the solution of protein Z. e. At a pH of 7, protein Z will be 50% protonated and 50% deprotonated.

e. At a pH of 7, protein Z will be 50% protonated and 50% deprotonated.

For the ______ represented by D-H.....A, the donor atom D is weakly acidic and the acceptor atom A is weakly basic. a. Acceptor b. Carbon bond c. Donor d. Hydrogen bond e. Electrostatic attraction

e. Electrostatic attraction

Solution X is at a pH of 5; solution Y is at a pH of 7. Which of the following is TRUE? a. Solution Y is more acidic than solution X. b. Solution X contains a lower concentration of protons than solution Y. c. Solution X is more basic than solution Y. d. Solution X contains 1000 more concentration of protons than solution Y. e. None of the answers is correct.

e. None of the answers is correct.

Which residues are MOST likely to be enriched in an intrinsically disordered protein that is soluble in water? a. E, C, F b. V, I, L c. Y, K, W d. H, F, W e. R, K, A

e. R, K, A

In the ______ form of hemoglobin, the iron ion is out of the plane of the porphyrin ring. a. R b. hydrogen bonded c. symmetry d. cyanosis e. T

e. T

At a pH above its pKa, the α-amino group of Lys is a. 50% charged b. racemic mixture. c. α-amino group. d. charged. e. deprotonated.

e. deprotonated.

Which one of these characteristics is not true for the α helix? a. There are 3.6 amino acids per turn b. Proline is typically not found in the α helix c. A hydrogen bond forms between the carbonyl oxygen of the nth d. amino acid residue and the -NH group of the (n + 4)th amino acid residue e. It is right-handed f. There is a requirement for glycine every third amino acid residue

f. There is a requirement for glycine every third amino acid residue