BioChem Exam 1

Which of the polypeptides is more water soluble at pH 7.0? (Gly)20 (Glu)20 They are equally soluble.

(Glu)20

What will the signs of the following thermodynamic parameters be? (pic in lecture 2 #8) -∆G, -∆S -∆G, +∆S +∆G, +∆S +∆G, -∆S

-∆G, +∆S

exothermic rxn and enthalpy

-∆H Release heat into the surroundings

What net charge will histidine have at pH 7? -2 -1 0 1 2

0

Which Ka is consistent with a base? 1/10 1/1,000,000,000 Neither More information is required

1/1,000,000,000

Tertiary (3˚) Structure

3D structure of a single amino acid polymer in its folded state

first law of thermodynamics

Energy cannot be created or destroyed only conserved from one form to another Energy is a constant within the universe

Gly

Lacks a chiral center.

protein folding

Molecular process in which proteins adopt specific 2˚, 3˚ & 4˚structures leading to a biologically functional protein

Amino acids are all chiral. all have a β-carbon. are all positively charged at pH 7.0. will all participate in hydrophobic interactions. None of the above statements are correct.

None of the above statements are correct.

Why is the α-helical conformation such a stable form? The α-helix structure is stabilized by hydrophobic interactions. The α-helix structure is stabilized by hydrogen bonds. The α-helix structure is stabilized by disulfide bonds. The α-helix structure is stabilized by proline residues.

The α-helix structure is stabilized by hydrogen bonds.

standard free energy (∆G′˚)

free energy under standard conditions ∆G′˚ = -RT ln Keq

β-strand

fully extended peptide chain that has a pleated appearance

Aromatic amino acids

phenylalanine, tyrosine, tryptophan

When a mixture of glucose 6-phosphate & fructose 6-phosphate is incubated with enzyme phosphohexose isomerase (which catalyzes the interconversion of these 2 compounds), until equilibrium is reached, the final mixture contains twice as much glucose 6-phosphate as fructose 6-phosphate. Which of the following statements is true? glucose 6-phosphate → fructose 6-phosphate A. ∆G′˚ = -1.72 kJ/mol B. ∆G′˚ = 0 C. ∆G′˚ = +1.72 kJ/mol D. ∆G′˚ is incalculably large & negative. E. ∆G′˚ is incalculably large & positive.

∆G′˚ = +1.72 kJ/mol

When a mixture of 3-phosphoglycerate & 2-phosphoglycerate is incubated at 25˚C with phosphoglycerate mutase until equilibrium is reached, the final mixture contains 6 times as much 2-phosphoglycerate as 3-phosphoglycerate. Which one of these statements is correct? 3-phosphoglycerate → 2-phosphoglycerate ∆G′˚ = -4.44 kJ/mol ∆G′˚ = 0 ∆G′˚ = 12.7 kJ/mol ∆G′˚ is incalculably large & positive. ∆G′˚ cannot be calculated from the information given.

∆G′˚ = -4.44 kJ/mol

enthalpy and heat

∆H = q

Titration of valine by a strong base, for example NaOH, reveals two pK's. The titration occurring at pK2 (pK2 = 9.62) is:

−NH+3⟶−NH2

What is the net charge of the following peptide at pH 3: Glu-His-Trp-Ser-Gly-Leu-Arg-Pro-Gly? -2 -1 0 +1 +2

+2

endergonic reaction

+ΔG Absorb free energy Nonspontaneous

Entropically-favorable

+ΔS

endothermic rxn and enthalpy

+∆H Absorb heat from the surroundings

The average charge of cysteine at pH 8.18 will be: -1 -0.5 +0.5 +1 None of the above

-0.5

What net charge will glycine have at pH 11? -2 -1 0 +1 +2

-1

exergonic reaction

-ΔG Release free energy Spontaneous

Enthalpically-favorable

-ΔH

What will the signs of the following thermodynamic parameters be? (pic in lecture 2 #7) -∆G, -∆H, -∆S -∆G, +∆H, -∆S -∆G, +∆H, +∆S +∆G, -∆H, -∆S +∆G, -∆H, +∆S

-∆G, +∆H, +∆S

What net charge will the predominant form of cysteine have at pH 7? -2 -1 0 +1 +2

0

What net charge will tyrosine have at pH 6? -2 -1 0 1 2

0

Which of the following aqueous solutions has the lowest pH? 0.1 M HCl (pKa = -8.0) 0.1 M acetic acid (pKa = 4.86) 0.1 M formic acid (pKa = 3.75) They all have the same pH.

0.1 M HCl (pKa = -8.0)

Cyrus Levinthal's Paradox (1968) assumptions

1) Assumption 1: 100 amino acid protein can be made in ∼5 seconds. →Derived from data in E. coli. 2) Assumption 2: Each protein can form only 10100 conformations. →10 Φ & Ψ angles for each amino acid. →Average protein ≈ 200-300 amino acids → UNDERestimate 3) Assumption 3: A protein conformation can be sampled every 10-13s. →Again, this is an arbitrary number picked by Levinthal. → OVERestimate

β-sheet/strand structural features

1) Pleated appearance 2) Side chain alternation from 1 side to the other →top polar, bottom non polar 3) Hydrogen bonding → helps form and hold strands together, acceptor = LP 4) Antiparallel (more stable) v. parallel → both in nature → N and C on opposite ends (ideal bonding geo) → N and C on same ends (parallel) 5) Torsion Angles →Antiparallel: Φ = -139˚, Ψ = 135˚, →Parallel: Φ = -113, Ψ = 113˚ 6) Connections between strands: >4 AAs

protein folding summary

1) Proteins fold via predetermined paths: Levinthal's Paradox 2) Paths are determined by the 1˚ structure: Anfinsen's Experiment 3) A single 1˚ structure leads to a single thermodynamically favorable native state 4) A protein will fold to minimize free energy (-∆G, - ∆H, + ∆S) 5) protein folding is entropically-driven

α-Helix structural features

1) Right-handed (nature) or left-handed 2) 5.4 Å pitch (Elevation gained for 1 complete turn of the helix) 3) 3.6 residues/turn (residue= amino acid in the context of a protein) 4) R-groups point away from axis 5) R-groups are offset from one another progressing down helix 6) Hydrogen bond exists between carbonyl oxygen of the Nth residue & the nitrogen of the N + 4 residue 7) Φ & Ψ torsion angles Phi (Φ) = -57˚ Psi (Ψ) = -47˚

Factors that affect α-helix stability:

1) Side chain identity Glycine & Proline→ disrupts formation high ∆∆G → short polar side chains (attract water) low ∆∆G → long side chains, weaken H bonds, less a helix 2) Side chain interaction Every 3rd to 4th residue will interact →same side of helix → ≤ 5.4 Å apart from each other ex. lysine with glutamate → ionic bond lysine with lysine → charge charge repulsion

Tertiary Structure of Myoglobin

1˚ Structure: 153 amino acids 2˚ Structure: 8 α-helices & connecting loops Heme prosthetic group

acidic amino acid class

2 neg charged at pH 7

protein misfolding

25% or more of all polypeptides synthesized may be destroyed because they don't fold correctly Alzheimer's disease, Huntington's disease, Parkinson's disease, Type II diabetes & transmissible spongiform encephalopathy arise from a common polypeptide misfolding mechanism In most cases, a soluble protein that is normally secreted from the cell is secreted in a misfolded state and converted into an insoluble extracellular amyloid fiber The diseases are collectively referred to as amyloidoses

basic amino acid class

3 predominant form at pH 7 histidine with ring and amino group

aromatic amino acid class

3 rings

insulin primary structure

3 disulfide bonds (1 intra, 2 inter) comes from preprocess insulin (bonds form then cleaves)

conformation

3D spatial arrangement of atoms within any molecule arising from the freedom of rotation of about a covalent bond Dihedral angle: angle between 2 intersecting planes (torsion angle) eclipsed, staggered

Quaternary (4˚) Structure

3D structure of a multi-subunit protein defining the spatial arrangements of each subunit with respect to each other Monomers, Dimers, Trimers, Tetramers & Beyond subunit interface:

The level of protein structure that describes all aspects of three-dimensional folding of a polypeptide is referred to as the 1˚ structure. 2˚ structure. 3˚ structure. 4˚ structure.

3˚ structure.

bond enthalpy depends on

4-48 kJ/mol depends on: 1) geometry 2) distance --> shorter bonds are stronger bonds 3) nature of surroundings: bonds are stronger in hydrophobic environments

polar amino acid class

5 predominant form at pH 7 disulfide bond/ bridge (cysteine) covalent bridge between 2 sulfides

non polar amino acid class

7 proline most restricted by structure

At what pH will HPO42- be the predominant form of phosphoric acid? (pic in lecture 2 #21) 1.5 4 7.2 8.5 13.0

8.5

Hydrogen bond

A bond that forms between two partial charges.

Ionic bond

A bond whose dissociation energy is inversely related to the polarity of the solvent and forms between atoms with formal charges.

Tertiary structures: of globular proteins would be destabilized by the mutation of a Phe, found in the core of the protein, to a Glu. are all stabilized by covalent long-range interactions. are not found in proteins that exhibit quaternary structure. unique features are dependent upon the primary structure. A), B), C), and D). A), B), and D). A) and D).

A) and D).

Several small aromatic molecules, such as phenol red, have been shown to inhibit the formation of amyloid in laboratory model systems. A goal of the research on these small aromatic compounds is to find a drug that would efficiently inhibit the formation of amyloid in the brains of people with incipient Alzheimer's disease. Why would molecules with aromatic substituents disrupt the formation of amyloid? A. Aromatic residues play an important role in stabilizing amyloid fibrils, molecules with aromatic substituents may interfere with the association of aromatic residues B. Molecules with aromatic substituents will interfere with the H bonds in the β sheets C. Molecules with aromatic substituents will interfere with the ionic interactions in the β sheets D. Molecules with aromatic substituents will cleave the peptide backbone, solubilizing the amyloid fibrils

A. Aromatic residues play an important role in stabilizing amyloid fibrils, molecules with aromatic substituents may interfere with the association of aromatic residues

List the following elements in order of increasing electronegativity: Hydrogen, Carbon, Nitrogen & Oxygen. A. Hydrogen < Carbon < Nitrogen < Oxygen B. Carbon < Hydrogen < Nitrogen < Oxygen C. Oxygen < Nitrogen < Carbon < Hydrogen D. Oxygen < Nitrogen < Hydrogen < Carbon E. None of the above

A. Hydrogen < Carbon < Nitrogen < Oxygen

Which is the correct equilibrium constant expression for the following reaction? C6H12O6 →2C2H5OH + 2CO2 A. Keq = [C2H5OH]2[CO2]2/[C6H12O6] B. Keq = [C2H5OH][CO2]/[C6H12O6] C. Keq = [C6H12O6]/[C2H5OH]2[CO2]2 D. Keq = [C6H12O6]/[C2H5OH][CO2]

A. Keq = [C2H5OH]2[CO2]2/[C6H12O6]

Glu

Acidic side chain

acids and bases

Acids: proton donors Bases: proton acceptors Conjugate base: base that forms when an acid donates its proton (A-)

amyloid beta peptide

Amyloid-β peptide is derived from a larger transmembrane protein called amyloid-β precursor protein (APP) APP is found in most human tissues & composed of 2 α-helical segments spanning the membrane gets cleaved between 2 Phe groups and turns bad forms beta sheets after alpha helix is cleaved characteristic plaques on exterior of nervous system tissue in pple with Alzheimers Amyloid is rich in β-sheet structure The structure takes the form of an extended 2-layer parallel β sheet Stabilized by Phe groups and their interactions (aromatic)

Which is more stable? Antiparallel β-sheet. Parallel β-sheet. Both are equally stable.

Antiparallel β-sheet.

Which solution will benzoic acid be more soluble in? (pic in lecture 2 #20) Aqueous 0.1 M NaOH Water pH 7.0 Aqueous 0.1 M HCl Benzoic acid will be equally soluble in all solutions There is not enough information

Aqueous 0.1 M NaOH

Which of the following amino acids has a net negative charge at pH 7.0? Glycine Threonine Aspartate Arginine

Aspartate

Given the data below determine which of the following statements is correct. At a pH of 2.5 the concentration of the conjugate base will far out weigh the concentration of the acid. At pH of 6.5 the concentration of the acid will far out weigh the concentration of the conjugate base. At a pH of 5.0 the conjugate base is the predominant chemical species in solution. At a pH of 4.76 the acid is the predominant chemical species in solution.

At a pH of 5.0 the conjugate base is the predominant chemical species in solution.

For the reaction A → B, the Keq = is 104. If a reaction mixture originally contains 1 mmol of A & no B, which of the following must be true? At equilibrium, there will be far more B than A. The rate of the reaction is very slow. The reaction requires coupling to an exergonic reaction in order to proceed. The reaction will proceed toward B at a very high rate. ∆G′˚ will be very large & positive.

At equilibrium, there will be far more B than A.

Which of the following titration curves represents glutamate? (pic in lecture 4 #4)

B

The ∆G′˚ of the reaction A→B is -60 kJ/mol. The reaction is started with 10 mmol of A; no B is initially present. After 24 hours, analysis reveals the presence of 2 mmol of B & 8 mmol of A. Which is the most likely explanation? A & B have reached equilibrium concentrations. An enzyme has shifted the equilibrium toward A. B formation is kinetically slow; equilibrium has not yet been reached after 24 hours. Formation of B is thermodynamically unfavorable. The result described is impossible, given the fact that ∆G′˚ = -60kJ/mol.

B formation is kinetically slow; equilibrium has not yet been reached after 24 hours.

Which of the following statements is true? The total change in enthalpy (ΔH) for a protein folding event must be negative because so many new electrostatic interactions form in the newly folded protein. The total change in enthalpy (ΔH) for a protein folding event can be negative if the protein forms disulfide bonds due to the net gain of covalent interactions not seen in the unfolded state. The total change in entropy (ΔS) for a protein folding event is estimated by considering the entropy of the peptide backbones conformation alone and as such must be negative. Ion-ion interactions are stronger in the hydrophobic core as compared to the same bond on the exterior of a protein. B) and D)

B) and D)

Some researchers have suggested that a drug used to treat Alzheimer's disease may also be effective in treating type 2 (adult onset) diabetes. Why might a single drug be effective in treating these two different conditions? A. Glucose metabolism and neurotransmission are very similar processes. B. The fundamental structure of the amyloid fibrils that cause both diseases are similar and similarly stabilized, so a drug that may disrupt the amyloid structure may be effective in treating both diseases. C. Amyloid is found in the brain in Alzheimer's disease and in the pancreas in type 2 diabetes, there will never be a drug that could treat both diseases. D. Who cares about these diseases; they are exceedingly rare.

B. The fundamental structure of the amyloid fibrils that cause both diseases are similar and similarly stabilized, so a drug that may disrupt the amyloid structure may be effective in treating both diseases.

Polyglutamate has the α-helical conformation at pH 3. When the pH is raised to 7, the α-helix unfolds. Why? A. The -OH ions break the peptide bond. B. The glutamate residues become negatively charged and repel each other. C. The glutamate residues become positively charged and repel each other. D. The glutamate residues become negatively charged and attract each other.

B. The glutamate residues become negatively charged and repel each other.

Which of the following experiments provided the 1st evidence that the amino acid sequence of a polypeptide chain contains all the information required to fold the chain into its native, three-dimensional structure? A. When ribonuclease is treated with urea, it loses its catalytic activity. B. When denatured ribonuclease is allowed to renature, it regains its catalytic activity. C. When renatured ribonuclease is allowed to denature, it regains its catalytic activity. D. Addition of mercaptoethanol causes ribonuclease to regain catalytic activity.

B. When denatured ribonuclease is allowed to renature, it regains its catalytic activity.

Hydrophobic interactions account for A. why biomolecules are amphipathic. B. why the nonpolar regions of molecules cluster together in water. C. the tendency of lipids to disperse in water. D. why the polar regions of molecules are associated with water.

B. why the nonpolar regions of molecules cluster together in water.

Net charge weird questions

Basic= Arg, Lys +1 (bc r group bigger than 7) Acidic= Asp, Glut -1 (bc r group smaller than 7) pKr groups = 0 charge when protonated

What is the determining factor influencing the stability of a protein? ∆G = ∆H -T∆S ∆H ∆S Both ∆H & ∆S Neither ∆H nor ∆S

Both ∆H & ∆S

Which bonds are planar (cannot rotate) in the polypeptide backbone? Cα-C bonds C-N bonds N-Cα bonds Cα-Cα bonds

C-N bonds

Aspirin is a weak acid with a pKa of 3.5. It is absorbed into the blood through the cells lining the stomach & small intestine. Absorption requires passage through the plasma membrane, the rate at of which is determined by the polarity of the molecule: charged & highly polar molecules pass slowly, whereas neutral hydrophobic ones pass rapidly. The pH of the stomach contents is about 1.5, & the contents of the small intestine is about 6. More aspirin is absorbed into the bloodstream from the (pic in lecture 2 #19) A. Aspirin is absorbed equally in the stomach and small intestine. B. Small intestine. C. Stomach.

C. Stomach.

Which of the following statements regarding ionic interactions is true? A. Ionic interactions are always stronger than covalent bonds. B. The strength of an ionic interaction is only dependent on the distance between the two ions. C. The force of attraction between two oppositely charged ions is lesser in polar solvents than nonpolar solvents. D. Ionic interactions will not form in nonpolar solvents. E. None of the above statements are true.

C. The force of attraction between two oppositely charged ions is lesser in polar solvents than nonpolar solvents.

The reaction A + B → C has a ∆G′˚ of -20 kJ/mol at 25˚C. Starting under standard conditions, one can predict that: A. at equilibrium, the [B] will exceed the [A]. B. at equilibrium, the [C] will be less than the [A]. C. at equilibrium, the [C] will exceed the [A] or the [B]. D. C will rapidly break down to A + B. E. when A & B are mixed, the reaction will proceed rapidly toward formation of C.

C. at equilibrium, the [C] will exceed the [A] or the [B].

Cys

Can form disulfide bonds.

Which of the following is true about carbon bonding: Carbon-carbon double bonds have rotational freedom. Carbon atoms can form covalent bonds with up to 4 other atoms. Carbon can form double bonds with hydrogen. Carbon-carbon single bonds cannot rotate. None of the above statements are true.

Carbon atoms can form covalent bonds with up to 4 other atoms.

Pro

Conformationally inflexible (relative to all other amino acids)

What is a disulfide bond? Covalent bond not found in all proteins Found in the amino group of proteins Found in the carboxyl group of proteins Found in aromatic R groups Found in nonpolar R groups

Covalent bond not found in all proteins

peptide bond

Covalent bond that holds amino acids together in peptides and proteins +∆G No acid-base chemistry in groups involved in peptide bond number of peptide bonds = n-1, n = amino acids

Which of the following pairs of groups cannot form a hydrogen bond with each other (the proposed hydrogen bond is indicated by the blue rectangle)? (pic in lecture 2 #10)

D

Which of the following is true about hydrogen bonds? A. Hydrogen bonds are longer & stronger than covalent bonds. B. The geometry of a water molecule results in equal sharing of electrons between the hydrogen and the oxygen. C. Hydrogen bonds must involve at least 1 water molecule. D. Polar molecules are soluble in water because they form hydrogen bonds with water molecules.

D. Polar molecules are soluble in water because they form hydrogen bonds with water molecules.

In glycolysis, fructose 1,6-bisphosphate is converted to 2 products with a standard free-energy change of (∆G′˚) of 23.8 kJ/mol. Under what conditions encountered in a normal cell will the free-energy change (∆G) be negative, enabling the reaction to proceed spontaneously to the right? A. Under standard conditions, enough energy is released to drive the reaction to the right. B. The reaction will not go to the right spontaneously under any conditions because ∆G′˚ is positive. C. The reaction will proceed spontaneously to the right if there is a high concentration of products relative to fructose 1,6-bisphosphate. D. The reaction will proceed spontaneously to the right if there is a high concentration of fructose 1,6-bisphosphate relative to the concentration of products. E. None of the above conditions are sufficient.

D. The reaction will proceed spontaneously to the right if there is a high concentration of fructose 1,6-bisphosphate relative to the concentration of products.

The components of poison ivy and poison oak that produce the characteristic itchy rash are catechols substituted with long-chain alkyl groups. (lecture 2 #18) 3-pentadecylcatechol pKa ≈ 8 If you were exposed to poison ivy, which of the treatments below would you apply to the affected area? A. Wash the area with cold water. B. Wash the area with soap and water. C. Wash the area with soap, water and dilute vinegar (acid). D. Wash the area with soap, water and baking soda (base).

D. Wash the area with soap, water and baking soda (base).

An α-helix is A. a feature of the peptide bond. B. a protein structural feature not found in myoglobin. C. a covalent or noncovalent interaction formed between amino acids far away from each other in the primary structure. D. a recurring backbone structural feature found in many proteins. E. a feature of the disulfide bond.

D. a recurring backbone structural feature found in many proteins.

A protein in solution is more likely to maintain its native conformation when A. the number of hydrogen bonds within a protein are minimized. B. the shell of water becomes more ordered. C. the protein is least stable. D. its hydrophobic residues are largely buried in the protein interior.

D. its hydrophobic residues are largely buried in the protein interior.

Conformations: A. Differ from one another in regard to the dihederal (or torsion) angles formed in them. B. Change only when a bond is broken. C. For any given molecule are all equally stable. D. Are labeled cis/trans when looking at double bonds. E. Are labeled R/S when looking at chirality. B), D), and E)

Differ from one another in regard to the dihederal (or torsion) angles formed in them.

dipole interactions

Dipole-Dipole: similar to H bonds, 1/r3 Charge-Induced Dipole: 1/r4 Dipole-Induced Dipole: 1/r5 Dispersion Forces: 1/r6

Energy of Ionic Interactions

E = Q1Q2/εr ε = dielectric constant (measure of the polarizability of the solvent)

You isolated a novel protein and measured the Φ & Ψ angles in this protein. What do you conclude about the protein? (lecture 5 #16) A. The only 2˚ structure found in this protein are right-handed α-helices. B. The only 2˚ structure found in this protein are left-handed α-helices. C. The only 2˚ structure found in this protein are β-sheets. D. This protein's β-sheets can only be anti-parallel. E. None of the above are true.

E. None of the above are true.

order of system decreases

Entropically favorable +∆S

order of system increases

Entropically unfavorable -∆S

Why is ethanol (CH3CH2OH) more soluble in water than ethane (CH3CH3)? A. Ethanol has a higher molecular weight than ethane. B. Ethanol can hydrogen bond with water better than ethane. C. Ethane can hydrogen bond with water better than ethanol. D. Ethane is more soluble in water than ethanol. E. None of the above.

Ethanol can hydrogen bond with water better than ethane.

In a β-sheet, β-strands must be the same length. True. False.

False

how is peptide bond formed

Formed by a condensation reaction between the amino group of 1 amino acid & the carboxyl group from another amino acid removes water!!!!

Non Polar amino acids

Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline

bond enthalpy

H , involved with first law of thermodynamics energy required to break a chemical bond ∆H = H(bonds broken) - H(bonds formed)

H bond acceptor H bond donor

H bond acceptor= oxygen with LPs H bond donor= hydrogen atom on electrneg atom

molecules that make up >99% of cell mass

H, C, N, O

α-Helix

Helical conformation of the peptide backbone with very specific structural properties 25-30% of peptide backbone takes up α-helical structure

Q and K

If Q > Keq ΔG + If Q < Keq ΔG - If Q = Keq ΔG 0 GRAPGHHHH

Which is not a feature of the peptide bond? Rigid Planar Covalent Partial double-bond character Ionic

Ionic

Replication: Is the process of making an RNA copy of a DNA gene. Is the process of making a protein from a DNA gene. Occurs in the nucleus of prokaryotes. Is required by all living organisms in order to make a complete copy of their genome. C) and D).

Is required by all living organisms in order to make a complete copy of their genome.

Translation: Is the process of making an RNA copy of a DNA gene. Is the process of making a protein from a DNA gene. Is the process of making a protein from a mRNA strand. Requires RNA polymerase. C) and D).

Is the process of making a protein from a mRNA strand.

Transcription: Is the process of making an RNA copy of a DNA gene. Is the process of making a protein from a DNA gene. Is the process of making a protein from a mRNA strand. Only occurs in eukaryotes. Can only produce one RNA product for each DNA gene.

Is the process of making an RNA copy of a DNA gene.

Under what conditions is a carbon atom a chiral center? A. If it has no stereoisomers. B. If the molecule that it belongs to can be superimposed on its mirror image after rotation. C. It has 4 different substituent groups. D. If it is symmetric. E. None of the above statements are true.

It has 4 different substituent groups.

water ionization

Keq = = 1.8 x 10-16 Ion product of water (KW): equilibrium constant of water ionization times the concentration of water

amino acid stereochemistry

L configuration (naturally occurring) D-configuration

Which of the polypeptides is more likely to take up an α-helical structure? A. LKAENDEAARAMSEA B. CRAGGFPWDQPGTSN C. IAHTTGPFGAAMCLT D. They are all equally likely to take up an α-helical structure. E. α-helices don't exist.

LKAENDEAARAMSEA

Dielectric constant

Measures the ability of a solvent to shield electrostatic interactions.

Electronegativity

Measures the ability of an atom to attract electrons to itself.

parts of peptide bond

N-terminus: 1st amino acid in the peptide & only amino acid with a free α-amino group C-terminus: last amino acid in the peptide & only amino acid with a free α-carboxyl group Peptide backbone: all atoms in a peptide excluding those found in the side chains

Would you expect the following sequence to adopt an α-helix at pH 7.0? KRAMKALRR Not enough information is provided Yes No

No

Does human insulin have quaternary structure? (lecture 5 #19) Yes No Quaternary structure does not exist. It is impossible to determine.

No (bc it gets cleaved bc preproinsulin) disulfide bonds stick the two chains together

The evaporation of a gallon of water on a summer day in the desert: will exhibit a negative enthalpy change. will exhibit a negative change in entropy. will exhibit a negative change in free energy. will result in a scenario in which the products have fewer hydrogen bonds than the reactants. will result in a scenario in which the products have greater degrees of freedom than the reactants. Only 3 is true. Only 4 is true. Only 5 is true. Only 3 and 4 are true. Only 3, 4 and 5 are true.

Only 3, 4 and 5 are true. pos dH, pos dS, neg dG

Resonance in the Peptide Bond

PICCC Covalent Partial double-bond character Rigid sp2 hybridization Planar between CO and CN peptide bond can't freely rotate bc partial double bond character bc resonance bc C-N BOND C-N bond!!!

diabetes

Pancreatic islet β cells are responsible for insulin secretion & regulation of glucose metabolism Healthy human adults have 1-1.5 million pancreatic β cells Progressive loss of these cells affects glucose homeostasis When 50% or more of these cells are lost, the condition matures into type II diabetes slow process but happening in everyone (fibrils growing, insoluble) fibrils starve off islet cells

Which of the 3 aromatic R groups is most hydrophobic? (pic in lecture 4 #1) Phenylalanine Tyrosine Tryptophan They are all equally hydrophobic

Phenylalanine

What dihedral angle is represented in this figure? (lecture 5 #4) Not enough information is provided Neither phi nor psi Phi (Φ) Psi (Ψ)

Phi (Φ)

torsion angles in peptide backbone

Phi (Φ): N-Cα Psi (Ψ): Cα-C

Which of the following will destabilize an α-helix? A. Placement of proline within the helix. B. Placement of glutamate 3 residues from an arginine within the helix. C. Placement of lysine 7 residues from another lysine within the helix. D. Omission of G from the helix. E. None of these conditions will destabilize an α-helix.

Placement of proline within the helix

Gibbs free energy (G)

Portion of the total energy of the system that can do work at constant temperature & pressure (free energy) G = H - T · S

His

Predominantly positively charged side chain at pH's below 6.01.

carboxyl group

R-COOH ↔ R-COO- + H+ Neutral Negative acidic

amino group

R-NH3+ ↔ R-NH2 + H+ Positive Neutral basic

Secondary (2˚) Structure

Recurring backbone structural patterns found in proteins

Cyrus Levinthal's Paradox results and conclusions

Results → It would take 1077 years to search all possible conformations. Conclusion →Protein folding MUST follow a predetermined path.

entropy

S, measure of disorder S = kB ln W, W=degrees of freedom (ways system can be arranged) ∆S = Sfinal - Sinitial All chemical & physical processes are headed toward equilibrium

primary structure

Sequence of amino acids in a polypeptide chain Description of all covalent bonds linking amino acids together in a protein (250-300 amino acids) 99% of these covalent bonds are peptide bonds

polar nature of water

Solid: 4 H bonds Liquid: 3.5 H bonds Gas: 0 H bonds

change in Gibbs free energy (ΔG)

The amount of energy released (-ΔG) or absorbed (+ΔG) in a reaction at constant temperature & pressure ΔG = ΔH - TΔS ΔG = Gfinal - Ginitial

Given the sequence of the peptide below state which of the following is true? Note: H3N+ is the N-terminal α-amino group and COO- is the C-terminal α-carboxyl group. H3N+-ASDPKRMH-COO-

The charge on the predominant species of the peptide at a pH of 7.4 is +1.

Transcriptome

The complete collection of gene products produced by transcription (and alternative splicing) within a cell.

Genome

The complete collection of genetic material within a cell.

Metabolome

The complete collection of low molecular mass molecules produced by metabolic processes in the cell.

Proteome

The complete collection of polypeptides produced by translation (and post-translational modifications) within a cell.

State which of the following statements is true for the molecule depicted below: A. The functional group in blue (on the right) could form ionic bonds. B. The functional group in red (on the left) could form ionic bonds. C. The functional group in blue (on the right) will be positively charged at all pH's. D. The functional group in red (on the left) is a hydrogen bond donor. A) and D).

The functional group in blue (on the right) could form ionic bonds.

Which of the following are true about protein folding? The formation of bonds is not important to protein stability. The delta H will never be negative for protein folding. The hydrophobic core is essential in stabilizing a protein. Only A and C are correct. A, B and C are correct.

The hydrophobic core is essential in stabilizing a protein.

What determines this predetermined path of protein folding? In other words, why does ribonuclease fold into ribonuclease & not myoglobin? Where does the information come from that directs this folding process? The information comes from the cell. The information is found within the protein itself. The information comes from the cell and the protein. The information comes from neither the cell nor the protein.

The information is found within the protein itself.

second law of thermodynamics

The universe always proceeds from a state of low entropy to a state of high entropy

Which of the following pairs does not represent a conjugate acid-base pair? RCOOH, RCOO- RNH2, RNH3+ H2PO4-, H3PO4 H2CO3, HCO3- They all represent conjugate acid-base pairs.

They all represent conjugate acid-base pairs.

Adjacent β-strands in a β-sheet can be several hundreds of amino acids away from each other in the primary structure. True. False.

True

In a β-sheet, there can be more than 2 β-strands. True. False.

True

The reaction below depicts micelle disruption. Considering this which of the following statements is true (assume the surroundings are aqueous)? Micelle ⇌ free fatty acid A. The sign on ΔG for the reaction as it proceeds from left to right will be negative. B. The change in entropy when the reaction proceeds from left to right will be positive. C. Water molecules will become more ordered if the reaction proceeds from left to right. D. The change in enthalpy for the reaction as it proceeds from left to right must be positive as it is an endergonic reaction. E. There is no way to determine what the sign will be on any of the thermodynamic terms.

Water molecules will become more ordered if the reaction proceeds from left to right.

Le Châtelier's Principle

When a stress is applied to a system at equilibrium the equilibrium will adjust to minimize the effects of the stress

Titration Curves & Buffers

[H+] Down (pH Up) [HA] Down [A-] Up Henderson-Hasselbalch equation: pH = pKa + log[A-]/[HA] pKa: pH when [HA] = [A-] pH above pKa: A- predominates pH below pKa: HA predominates

At the center of all the 20 standard amino acids is what is termed the α-carbon that is covalently bonded with 4 other chemical groups. Which of these 4 groups is not a normal component of all amino acids? an amino group a carboxyl group a side chain (R group) a methyl group

a methyl group

spontaneous reaction

a process that occurs without work being done to bring it about. A reaction that, given initial conditions, will proceed in the direction of the production of products to reach equilibrium.

Christian Anfinsen's Experiment

added urea and BME to unfold and refold protein 1) Protein folding is spontaneous: -ΔG. 2) All the information that is needed to fold a protein is found in the 1˚structure. 3) Protein folding is accurate, specific & reproducible.

amino acid general structure

alpha carbon center (chiral) amino group carboxyl group R group hydrogen

amino acid nomenclature

amino acid name 3 letter abbreviation 1 letter abbreviation

The amino acid alanine contain all of the following functional groups except: an amino group. a methyl group. an ester group. a carboxylate group. Alanine contains all 4 of the above functional groups.

an ester group.

chaperone

any protein that assists another protein in adopting its final structure while not becoming part of that structure prevents proteins from getting off course

Secondary structures: are stabilized by the hydrophobic core. like α-helices, can be disrupted by the placement of oppositely charged side chains four residues away from each other. are stabilized by hydrogen bonds formed by hydrogen bond acceptors and donors found in the backbone. are formed when subunits come together. B) and C).

are stabilized by hydrogen bonds formed by hydrogen bond acceptors and donors found in the backbone.

acidic amino acids

aspartate, glutamate

dipole

asymmetric distribution of electrons within a covalent bond

Which element is most abundant (by mass) in dehydrated cells? Hydrogen Carbon Nitrogen Oxygen

carbon

metabolites

compounds that are intermediates and products of metabolic pathways ex. in glycolysis

Long-range interaction

covalent or noncovalent interaction between side chains that are far from one another in the 1˚ structure, but in close proximity in the 3˚ structure ex. ribonuclease disulfide bonds

prions disease

death by misfolding Diseased brain becomes riddled with holes natural conformer vs rouge conformer ex. mad cow disease, kuru, scrapie

entropy change

describes the change in the system's randomness: positive if reaction increases system's randomness ΔS

configuration

differing 3D spatial arrangements of atoms within molecules that have the same chemical makeup or molecular formula differing in two ways: 1) arrangement of atoms about a double bond (geometric isomers) 2) arrangement of atoms about a chiral center (stereoisomers)

glycine

does not have 4 different groups bound (NOT chiral)

hydrogen bond aspects

donor: hydrogen bound to electronegative atom (hydroxyl, amino) acceptor: lone pair on electronegative atom

hydrogen bond

electrostatic interaction between a lone pair on 1 electronegative atom & the hydrogen covalently bonded to a separate electronegative atom. No sharing of electrons as seen in covalent bonding.

Ionic interaction

electrostatic interaction between two ions

What drives the hydrophobic effect? Enthalpy Entropy The hydrophobic effect doesn't exist.

entropy

Living systems

far from equilibrium or irreversible ex. water flowing to other side after gate is opened

β-Turns and Loops

four amino acid segment that connects two β-strands ex. Ribonuclease: 35% β-sheet, 26% α helices, 39% loops

native state

fully folded & functional state of the protein

protein folding diagrams

funnel → not accurate bc its NOT a smooth pathway with no intermediates protein folding funnel → more realistic bc of folding intermediates, red arrows are bad bc misfolding final version → inter and intra, chaperones

proteome complexity

genome (25,000 genes) mRNA editing, alternative splicing transciptome (100,000 transcripts) post-translational modifications proteome (1,000,000 proteins)

Subunit

individual polypeptide that comes together with another subunit(s) to form a functional protein neg and pos charges and non covalent interactions help hold together

Hydrophobic core

interior of a globular protein that consists primarily of hydrophobic side chains tertiary

The chirality of an amino acid results from the fact that its ∝ carbon:

is bonded to four different chemical groups.

stereoisomers

isomers resulting from the different spatial arrangements of atoms about a chiral center. chiral center: atom with 4 different chemical groups bound

geometric isomers

isomers resulting from the different spatial arrangements of atoms across a double bond. Also called cis/trans isomers.

A protein is in its native conformation when it is thermodynamically least stable. it has the highest Gibbs free energy. it is in its functional, folded state. it is unfolded.

it is in its functional, folded state.

macromolecules

large molecules found in biological systems whose molecular mass exceeds a few thousand g/mol ex. proteins, nucleic acids, carbs, lipids

basic amino acids

lysine, arginine, histidine

For the following reaction, ∆G′˚ = +29.7 kJ/mol. L-malate + NAD+ → oxaloacetate + NADH + H+ The reaction as written: A. can never occur in a cell. B. can occur in a cell only if it is coupled to another reaction for which the ∆G′˚ is positive. C. cannot occur because of its large activation energy. D. may occur in cells at some concentrations of substrate & product.

may occur in cells at some concentrations of substrate & product.

electronegativity

measure of the ability of an atom to attract electrons to itself in covalent bonds

Clathrate cage

molecular interaction water molecules will adopt when surrounding a hydrophobic molecule

Amphipathic

molecule with domains of 2 different natures polar head, hydrophobic tail

Which of the following mutations is likely to have the most detrimental impact on the stability a protein structure: mutation of an Asn that is found on the surface of the protein to a Gln. mutation of a Leu that is found in the hydrophobic core to a Val. mutation of a Ser that is found on the surface of the protein to a Cys. mutation of a Glu that is found in the hydrophobic core to a Leu. mutation of an Arg that is forming an ionic bond with a nearby Glu to Lys.

mutation of a Glu that is found in the hydrophobic core to a Leu.

What is ∆G′˚? (graph in lecture 1) Negative Positive 0 Impossible to tell

negative

Which of the following statements are true regarding the metabolome, the proteome, the genome, and the transcriptome? The number of genes found in the genome equals the number of different proteins that can be made within any give cell. The number of transcription products equals the number of proteins that can be made from these transcription products. The number of genes found in the genome equals the number of different transcription products that can be made within any given cell. The metabolome is encoded by the genome. None of the above.

none of the above

Prosthetic group

nonprotein molecule that is permanently associated with a protein & is essential for its function

hydrophobic effect

observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules ex. Plasma membrane, protein folding, oil & water

The Importance of pH & Macromolecular Structure/Function

pH & Enzyme Function see pics in chapter 2.7

titration of glycine ex

pKa values are environment-dependent

amino acid titration

pk1→ COOH =2 (depro) pk2→ NH3 =9-11 (pro) pkR→ R group acidic= neutral → neg basic= positive → neutral

Ramachandran plot

plot of the psi (Ψ) vs. phi (Φ) angles of each amino acid in a given protein (phi vs psi) darker= greater likelihood of there being phi and psi angles

Domain

portion of a polypeptide chain that is structurally & functionally independent of the rest of the protein can oppose activities on a protein ex. PFK-2/FBPase-2

polarity

property of a molecule that has an overall dipole

enthalpy change

reflects kinds & numbers of chemical bonds & interactions broken and formed: negative if reaction releases energy ΔH

polar amino acids

serine, threonine, asparagine, glutamine, cysteine

Rotamers

set of preferred dihedral angles each amino acid side chain will adopt (Ca, Cb, ect)

hybrid orbitals

single bonds and sp3, tetrahedral and 109.5 multiple bonds and sp/sp2, trigonal planar geometry, 120

buffer

solution consisting of a conjugate acid/base pair that resists large changes in pH in a titration

amyloid fibril

stable (golfing, can't get ball out of hole), irreversible process but slow, extended beta sheet structure (parallel) can grow indefinitely (bc some Hs not participating in H bonds) and bigger is more problematic intermolecular H bonds between beta strands betan strands perpendicular to fiber axis

Which conformation of ethane is most stable? Staggered Eclipsed Both eclipsed & staggered are equally stable. This remains a scientific mystery.

staggered

β-sheet

structural pattern in which β-strands interact with each other to form a sheet

Protein backbone conformation

summation of each amino acid's phi (Φ) & psi (Ψ) angles

Motif

super-2˚ structure, fold, a distinctive & recurring form, shape, figure, etc. recurring 3D spatial arrangement of structural patterns within a protein that consists of 2 or more 2˚structural elements & their interconnecting loops ex. Pyruvate kinase, β-α-β motif

-increase the entropy of the universe -use energy to maintain order

tendency of a reaction to go to completion The ratio of the concentration ([]) of products over the concentration of the reactants at equilibrium

peptide bond configurations

trans: 99%. cis:1% trans is thermodynamically preferred to reduce steric hinderance exception is when proline is involved trans: 75-80%. cis: 20-25%

Globular protein

typically found in aqueous environments & have a globular or spherical structure tertiary structure

denatured state

unfolded & non-functional state of the protein Unfolded state Random coil

changes in conformation occur

when covalent bonds are broken

amino acid

α-amino substituted carboxylic acid building blocks of proteins carbon is sp3 hybridized tetrahedral geometry 109.5˚ bond angles alpha carbon is chiral R group differentiates the amino acids

occur when polar molecules are attracted to one another

ε, measure of the polarizability of the solvent ε is high for polar solvents (78.5 for water) ε is low for nonpolar solvents (4.6 for benzene & interior of many proteins) Ionic interactions between dissolved ions are much stronger in less polar environments and weaker in highly polar environments

actual free energy

∆G = ∆G′˚ + RT ln Q Q= determines the actual driving force of the reaction and which direction it will proceed to reach equilibrium at conditions prevailing in the cell. Q= mass-action ratio = [P]/[R]

ribonuclease stability

∆G = ∆H -T∆S Entropy of folding 1) Conformational entropy: -∆S 2) Solvent entropy: +∆S 3) Total entropy: +∆S

protein stability

∆G = ∆H -T∆S Things that can make ∆H negative: 1) Disulfide bonds: ∆H = HBB - HBF 2) Ionic interactions →Buried ionic interactions →Energy of Ionic Interactions = E = Q1Q2/εr ε is high for polar solvents (78.4 for water) ε is low for nonpolar solvents (∼4 for interior of a globular protein)