Amino Acids Flashcards
Why does the discovery of RNA as a genome violate the central dogma?
DNA is historically thought to be the central core. To support the linear progress of the process. RNA as the core violates this
How does the discovery of Retroviruses (such as HIV) violate the central dogma?
1970 - discovery found that RNA as genome. They utilize reverse transcriptase to create DNA. It challenges the idea of linear polymer in which DNA is a template -> RNA -> Protein
In the traditional central dogma theory, which polymer is the functional unit of life to the cell?
Proteins
Even though the traditional central dogma theory has been accepted largely for a long time, how does the idea of linear polymer contradict this ideal? What does it hint?
Part of the linear polymer ideal state that templates exist at every molecular stage (DNA, RNA, and pro-). This hints that conversion form one polymer to the next is not linear, but can also go backwards too.
What were Rosalind Franklin’s contributions to the discovery of the double helix of DNA?
Rosalind Franklin actually measured and captured the helix of DNA in her XRay diffraction of DNA. Crick and Watson utilized her info to draw their own conclusions.
How does Marshall Nisenberg define the central dogma discovered by Crick and Watson?
DNA can self replicate
DNA can also be transcribed to RNA and RNA is then translated into protein
How is DNA replication different from DNA transcription?
DNA replication is the process in which DNA gets stored as DNA for another/new cell. DNA transcription is the process in which DNA is converted into RNA.
How can you utilize language in a way to differentiate the difference between transcription and translation?
Transcript: The same alphabet. One text written to another. DNA -> RNA. Nucleotide -> Nucleotide
Translation: One language to another. RNA -> Pro- (nucleotide -> amino acids)
DNA, RNA, and protein are considered linear polymers. What doe s that mean? What is its significance in terms of central dogma?
Single units of each are attempted at most to at most to others. This gives a sequence and allows a template to exist. The template assures information is accurate encoded and passed on.
Explain to different cells as a RBC and a fat cell have a different phenotypes, function, dominant metabolic pathways, etc. If they share the same DNA copies. Name examples of these processes.
Modification of the genome results in different in different phenotypes.
Such epigenetic mechanisms are DNA methylation and histone modification
How are epigenetics a violation of the traditional view?
The study if heritable changes in gene activities demonstrate how DNA, the central blue print, can be altered. This idea is not present with traditional views. The traditional view focuses on changes in phenotype only by change in genotype.
What are the functional differences between cDNA and ncRNA? What processes do they tend to be associated with?
cDNA is generated in the process of RNA reverse transcribing to DNA, in which enzyme reverse transcriptase adds on complimentary DNA to the RNA template
ncRNA are non coding RNA that do not require translation into proteins to become functional. (Per the traditional view of central dogma) Instead RNA can become functional. Ex: tRNA and rRNA
Along with epigeneitcs and reverse transcription violating. What other two processes/ideals violate the theory
RNA as genomes and non-coding RNAs
Besides these 3 functions: catalysts, structural, and transport, what other function do proteins have?
Immunity, communication, mobility
Link the idea of linear polymers to amino acids and proteins.
The primary structure of proteins are composed of a linear polymer. Units of an amino acid sequentially linked through peptide bonds sequentially.
True or False: The secondary structure of a protein contributes to the folding a molecule.
False. Sequence of an a.a determines the 3 dimensional structure as it folds spontaneously
There are only 20 different types of amino acids in the human body. What makes each amino acid different from the next?
The R Group
In general, what does the R group of an amino acid determine about that molecule?
R groups determine the capability, reactivity, solubility and overall charge of the amino acid
In terms of amino acids, how does it affect the function of a protein?
Arrangement and sequence of amino acids affects the function of a protein
What is the purpose of an R group in an active site of a catalyst?
R groups are especially important in enzymes as they can carry out different reactions to speed up the reaction
Different amino acids have different rigidness in characteristics compared to others. Name an example regarding cell structure in which rigid amino acids would be used over a flexible amino acid
The cytoskeleton - gives structure to the cell and can’t bend (would be done with a flexible a.a)
True or False: Proteins are functional and can act alone in delivering reaction without the assistance of others.
False. Proteins tend to not act alone. They usually from functional complexes with macromolecules and other proteins.
Give the molecular explanation as to why amino acids are referred to as alpha amino acids.
They’re named by the chiral carbon attached to the carbonyl group.
How many alpha amino acids exist in the body?
A. 10
B. 20
C. 9
D. 12
B. 20 There are 10 essential amino acids (means the body can not make these itself). But alpha amino acids ≠ essential. The definition simply means that an alpha amino acid is attached to 4 groups: H, NHx, COOx and R group. Therefore all 20 a.a found in body are alpha a.a
The human body tends to be at a neutral pH uniformly. how does this affect the carbonyl and amino acid group of an amino acid in terms of protonation and deprotonation?
COOH -> COO-
NH2 -> NH3
The amino acid will tend to exist as a Zwitterion species
All amino acids have a S configuration except:
A. Gln
B. Thr
C. Try
D. Cys
D. Cysteine, Cys, C. A.a has a sulfur which shifts the priority to it rather than to nitrogen. This causes it to have an R configuration while all others have a S configuration in absolute configuration. Even though cysteine has R configuration, it still shares and L configuration like all other amino acids
In figuring absolute configuration of a molecule, what is used to assess priority:
A. Proton and neutron
B. Protons
C. Electrons
D. Atomic Mass
B. The atomic number is used to give priority which is the number of protons of the element.
Does dipole have any relation to a Zwitterion species of an amino acid?
Yes. When an amino acid exists as a zwitterion species, this molecule has two dipole moments both + and - and is considered to exist in its dipolar forms
The protonation of an amino group and a carboxyl group on an amino acid is determines by…
A. The folding of a protein
B. The activity of an enzyme
C. Available H’s within a solution
D. Available OH’s within a solution
C. pH of a solution determines protonation/deprotonation therefore available protons
pH of 4 is considered acidic or basic within the body? What protonation of carboxyl are at this pH?
This is considered a neutral pH. Amino acids start entering their zwitterion species with COOH -> COO- and NH2 -> NH3+
At a pH of 1, what is the expected amino acid charge species existing at this environment?
Positive species with COOH and NH3+
True or False: pH4 is the condition in which positively charged amino acid species begin to lose H+ on COOH to form zwitterions.
False. At pH2, COOH begins to dissociate. At pH of 4-7, most amino acids exist as zwitterion species.
True or False: At pH of 7, amino acids experiencing dissociations of H+ from amino group to form negatively charged species.
False: This is seen at pH of an a.a pH of 7, amino acids still in their zwitterion species.
All of the following help determine the physical and chemical properties of a side chain except:
A. Size
B. Structure
C. Ability to oxygen bond
D. Ability to hydrogen Bond
C. The ability to oxygen bond
Which of the following helps determine the physical and chemical properties of an amino acid:
I. Shape
II. Polarity
III. Hydrophobic Properties
IV. Charge
A. I Only
B. I and II
C. I, II, and IV
D. I, II, III, IV
D. All determine chemical and physical properties of a side chain in an amino acid
Below is a list of quantities that play a significant role in determining the chemical and physical properties of a side chain in an amino acid. Choose the ones that are not essential
- Melting points 2. Size 3. Polarity 4. Ability to hydrogen bond 5. Ability to conduct electricity 6. Structure 7. Shape 8. Charge 9. Hydrophobicity 10. Boiling Points
- Melting Points
- Ability to Conduct Electricity
- Boiling points
True or False: Amino Acids linked together by peptide bonds form proteins and single proteins this fold to form polypeptide chains
False. Polypeptide are made by linked amino acids which fold to form proteins.
Peptide bonds are formed by what reaction? The electrons from which atom initiates the reaction?
Nucleophilic - Addition - Elimination
Usually through an attack of an electronegative atom on the carbonyl carbon, breaking the carbonyl double bond and forming a tetrahedral intermediate.
Peptide Bonds are considered rigid and inflexible due to what?
Due to resonance. Nitrogen’s electrons are able to contribute to the resonance and delocalize the double bond in the carbonyl
True or False: Because the peptide bonds w/n an polypeptide chain are rigid and planar, the polypeptide chain as a whole is linear as a result.
False. Alpha Carbons are able to freely rotate and bend and allow folding to form a protein
A peptide bond is essentially an amide bond formed between 2 amino acids. This creates a uniform backbone with most proteins. What is this pattern within the backbone?
N - α C -CO - N - α C - CO - N - αC - COOH
The pattern in peptide formation creates a N terminus and a C terminus within all polypeptide chain
What is the specific name for each amino acid within a polypeptide chain called?
A residue
The breakdown of a peptide bond to form to amino acids.chains is called hydrolysis. What is the specific and nonspecific hydrolysis of a peptide bond?
Proteolysis and acid hydrolysis
In acid hydrolysis, what two factors are utilized within the reaction to break a peptide bond?
- Strong Acids
2. Heat
How is acid hydrolysis different in outcome from proteolysis?
Acid hydrolysis clears all peptide bonds creating only individual specific cleavages between specific amino acids to form certain chains
Name all the required reactants for proteolysis to occus
Polypeptide chain and protease(s)/proteolytic enyzme(s)
You are analyzing a protein and want to cut the polypeptide chain into smaller chunks. You add trypsin knowing the enyzme only cleaves basic amino acids like arginine and lysine. What is the end result with the following chain.
N term - Thr - Arg - His - Pro - Lys - Val - C Term
Thr - Arg
His-Pro-Lys
Val
Histidine’s side chain has a pKa 6.5, which is very close the physiological pH of 7.4 How does this affect Histidine’s charge at pH of 7.4?
This causes Histidine to be in both a deprotonated and protonated species
Differentiate pH and pKa.
pH is the measurement of available H+ molecules in an environment.
pKa is the measurement of how easily a molecule gives up its hydrogen atom
Protonation and deprotonaton of a molecule, such as an amino acid, depends on its pKa to is environmental pH. Decipher what the molecule’s state will be in the conditions below:
i. pH > pKa
ii. pH < pKa
i. Deprotonation
ii. Protonated
Histidine’s R group’s unique pKa of 6.5 allows it to play an important role w/n enzymes. What can it do?
Histidine stabilizes and destabilizes a substrate during reaction
Alpha helix breakers are amino acids that disrupt the secondary folding of a polypeptide chain with a kink. Names all the amino acids responsible for this.
Proline and glycine
Proline is referred to as a secondary alpha amino group. What does this entail?
It states that the R group of the amino acid attaches back to the amino group of the molecule
Upon examination of proline, it is obvious that the bulky side chain will disrupt an alpha helix coil. Why is glycine also considered a contender in this disruption?
As glycine has a small side chain (H) it has lots of flexibility at alpha carbon. This free rotation could cause kinks as well as it rotates within the helix
Differentiate cysteine from cystine. Are they the same thing?
Both are the same molecule. One is with electrons in its reduced form (cysteine). The other without, in its oxidized form (cystine)
Mnuemonic - “e for electrons”
The formation of disulfide bridges between 2 cysteine amino acids is due to:
A. Peptide Bond
B. Acid Hydrolysis
C. Electron Transfer
D. Nucleophilic Substitution
C. Electron Transfer. The two thiol groups (-SH) Join through a redox reaction in which both share electrons covalently
True or False: Disulfide bridges between 2 cysteine amino acids can only be formed in oxidizing environment/following an oxidation.
True
Disulfide bridges are more likely to form within the intracellular matrix or in the extracellular matrix. Why?
Extracellular because the environment is more oxidizing compared to intracellular
Antioxidants are stored within the cell. How can the meaning of the word help remind you of the environment as reducing
Anti-oxidant - these are kept within cell or ICM
Anti - not oxidizing.
ICM - reduced env. therefore not oxidizing
Amino acids are chiral due to the α carbon. This means it has optical activity. What does optical activity mean?
In testing a substance, as you shine light onto it, if the substance rotates the light, it polarizes a plane. This is only seen in chiral molecules. [chiral molecules - molecules with an attachment with 4 different groups]
Optic activity of a molecule or the rotation of light is dependent on what?
It depends on the stereochemistry/configuration of the molecule = L or D. L Molecules rotate light in (-) or left direction and D rotates light in (+) or right direction
What is the use of the fischer projections?
Fischer projections are another method in illustrating molecules and is most useful stereochemistry/absolute configuration.
Intersection - chiral carbon
Horizontal attachments to the chiral carbon are coming out to the page
Vertical Attachments go into the page
Apply the idea of enantiomers to amino acids found in the body. What does this mean?
Enantiomers are molecules that are mirror images BUT are not superimposable. Therefore L&D or R&S amino acids are enantiomers
Compare and contrast L/D & R/S configuration. Utilize amino acids as your example
L/D = Relative configuration R/S = Absolute configuration
L/D are concerned about the configuration of one group within the molecule. Such as L-amino acids have the amino group on the left hand side. R/S take into account of all groups attached to a carbon and gives them priority before assessing if the molecule is R/S
What type of amino acid configuration is found most commonly in the human body?
A. R Configuration
B. L Configuration
C. D Configuration
D. S Configuration
B. L - configuration
What is the isoelectric point for glutamic acid with α carbonyl (α-COOH, pK1 = 2.19), α-amino (α-NH3+, pK2 = 9.67), and R group (R-COOH, pKR = 4.25)
A. 2.19
B. 3.22
C. 6.02
D. 7.45
B. 3.22
(4.25 + 2.19)/2 = 3.22
Zwitterion exists between 4.25 and 2.19
The isoelectric point is:
A. The overall neutral charge of an amino acid at a pH
B. A state in which an amino acid contains both a negative and positive charge
C. When an amine group of an amino acid is protonated and the carboxyl group is deprotonated
D. The pH of an amino acid when its overall charge is neutral
D. Isoelectric point is a pH
Both are B & C definitions of a zwitterion. C is specifically a zwitterion of an amino acid
Define Isoelectric
Equal charge
Why is it important to understand the isoelectric point of an amino acid?
Understanding the pH/pI (Isoelectric pt) allows us to know how the amino acid over protein will function at certain point
How is a zwitterion different from a neutral molecule?
Zwitterion is specifically in regards a molecule contain both a (-) and (+) charge, both canceling out. Neutral can mean no charge exists within the molecule ≠ Zwitterion
Find the PI (isoelectric point) of a molecule is the α amino grp has a pKA of 9 and the α carboxyl group has a pKa of 2.
PI = (pKa1 - pKa2) /2 PI = (2+9)/2 = 11/2 = 5.5
True or False: When an amino acid has a R group with a pKa, this number can be ignored in assessing the PI as the PI takes into account pKas of the highest and lowest
False. PI takes into account of the closest pKas to the zwitterion. Therefore this can be the average between the amino pKA and the R group pKA or the average between the carboxyl pKA and the R group.
The pKa of COOH in glycine is 2.34. What does this mean?
At a pH of 2.34, the COOH of the amino acid will be deprotonated 50% and the protonated by 50%
The rule of thumb for amino groups and carboxyl groups pKas are 2 and 9 respectively. Identify which amino acid(s) are the highest and lowest to each pKa
Lowest NH2 pKa: Phe (F) - 1.83 and His (H) - 1.82
Lowest COOH pKa: Cys (C) - 8.18
Highest NH2 pKa: Leu (L) - 2.36 and Iso (I) - 2.36
Highest COOH pKa: Pro (P) - 10.60
Mnemonic: Both NH2 and COOH share subtracting a value and adding value*2.
NH2 value: 0.17 | For Him, I Love
COOH value: 0.8
How are the amino acids classified? Schematically illustrate this. What characteristics/physical properties are there classification based on?
Amino Acids - Non polar and Polar
Non polar - Alkyl and Aromatic
Polar - Neutral, acidic, and basic
Physical properties of division: Hydrogen bonding, acidic vs basic charge
Is the dissociation of the R group in amino acid related to the activity of the amino acid?
No necessarily. Neutral/uncharged polar amino acids (Serine, Threonine, Asparagine, Glutamine, and Cysteine) have no pKa for their R groups but are able to undergo chemical reactions
What type of amino acids change their name after the deprotonation of their R groups. Notate their full name, 3 letter abbreviation, letter symbol and illustrate the amino acid.
Acidic, Polar amino acids change their name.
Aspartic Acid: ASP (D) -> Aspartate
Glutamic Acid: GLU (E) -> Glutamate
Mnemonic: Acids are acidic
Which 2 amino acids have more than 1 chiral center? What configuration do they exist in?
Isoleucine (Iso, I) - L-Isoleucine is found in the body
Threonine (Thr, T) - L-Threonine is found in the body
Mnemonic: α and β carbons are chiral. One due to a methyl group and OH group
Explain the ambiguity of tyrosine’s classification. What categories does it/can it fall under? What other structurally similar amino acid is like tyrosine?
Having a hydroxyl group on its benzene allows the amino acid to be slightly more acidic than its counter part phenylalanine. Therefore tyrosine can fall under non polar aromatic or polar neutral
Tryptophan, also shares this, however it falls under non polar aromatic more often
How does Valine and Leucine differentiate. How are they the same?
Both are hydrophobic acids and fall under the nonpolar, alkyl group. They differ by 1 hydrocarbon
Explain why methionine is considered non polar while cysteine is a polar molecule when both share the same element: Sulfur
Electronegativity: S - 2.58 & C - 2.55
Methionine - Even as met is slightly more EN, the pulls are evenly distributed bt sulfur & carbon -> met - non polar
Cysteine - The bond bt sulfur & hydrogen creates a big dipole moment, allowing cysteine to be more polar
How can an amino acid be considered polar and neutral? Use Serine as your example.
Serine is uncharge because the H on the OH doesn’t dissociate from the amino acid. (seen in all neutral polar amino acids) However, there does exist a dipole moment! This allows the amino acids to exist comfortably in water
What element do all basic amino acids share?
Nitrogen - Nitrogen is a good proton acceptor and thus act as a “base”
Acidic Amino acids are negatively charges amino as a basic amino acids are…
Positively charges amino acids in neutral pH, their R group dissociates => a =/- charged R group
Rule of thumb =>
Acidic: - charged (O gives off H => negative charge)
and Basic: + charged (N accepts H => positive charge)
What are special side chain or special side amino acids?
Cystine! BC of their ability to form disulfide bridges
Draw out a carboxamide group. What amino acids have them?
Only asparagine, Asn, N has this group. Consist of an amide of a carboxylic acid, having the structure R: CH2-CO=NH2
What role does electronegativity have on hydrophobicity? How does mass effect electronegativity? Use hydrocarbon as your example.
Hydrophobicity is determined by concentration of electron in certain areas of the molecule (dipole moments). When a molecule has their interactions they have the ability to interact with water. Therefore no dipole = hydrophobic. Dipole moments are created by EN (the pull of e- to a nucleus). The EN creates polarity/hydrophobicity.
As the mass of a nucleus increases, the electron on the outer shell have increase distance from the nucleus therefore decrease in EN with increase mass as there is in an increase in hydrocarbons on an amino acid. Therefore decrease in EN and in crease in hydrophobicity
Define what an indole is. What amino acid has this functional group?
A benzene infused with a pyrole (5 membered ring with 4 C’s and either a O, N, or S) such as a tryptophan
How many amino acids are nonpolar? Name them all with their 3 letter abbreviations and symbols. What physical properties do these share?
7 total amino acids - these are unreactive and hydrophobic and neutral.
1. Glycine, Gly, G 2. Alanin, Ala, A 3. Valine, Val, V 4. Leucine, Leu, L 5. Isoleucine, Iso, I 6. Proline, Pro, P 7. Methionine, Met, M
Mnemonic: Juan always says that when Gato is not wet, she is a LIMP-VAG
Mnemonic for remembering the aromatic amino acids
If you want a WYFm you have to put a RING on it
Tyrptophan, Try, W
Tyrosine, Tyr, Y
Phenylalanine, Phe, F
Mnemonic for remembering the nonpolar, alkyl groups (aka neutral unreactive grp)
Juan always says that when Gato is not wet, she is a LIMP-VAG
Leucine, Isoleucine, Methionine, Proline, Valine, Alaine, Glycine
Compare to arginine, what about lysine’s R group causes it to become protonated at a much lower pH.
Lysine has no resonance like arginine. ASN can balance the electrons within it 3 nitrogens and therefore it much more stable at/in a protonated form
Lys - pKa - 10.8
Arginine - pKa - 12.5
What are ionizable groups? How are they demonstrated in amino acids?
The groups simply play a role in either accepting or donating a hydrogen atom. 7 amino acids: Acids, base,+ cysteine & tyrosine are ionizable therefore ability in donating/accepting H+ => charge on the a.a/once charged they are able to create ionic bonds
True or False: Only acidic or basic acidic amino acids have the ability to dissociate, therefore they are the only capable a.a in forming ionic bonds with other molecules
False. Cysteine or tyrosine are neutral, however they have the ability to deprotonate and once the charge is formed, can also play a role in ionic bonds
Cysteine’s pKa is at 8.3. Denote the changes cysteine undergoes at this pH. Which is the ionizable form?
At pH 8.3, the H on the Sulfur depronates, resulting in the amino acid to have an overall negative charge. This negative form is also the ionizable form of the the amino acid
Even as tyrosine’s R group does have a pKa value and therefore division, what is unique about tyrosine that is not seen in other ionizable amino acids
pKa - 10.9
Tyrosine’s R group is still very nonpolar therefore hydrophobic. Therefore the ion form occurs within the protein while many other amino acids form ionic bonds outside of the protein.
The formation of a peptide bond between to amino acids is all following except: A. Hydrolysis B. Covalent Bond C. Dehydration D. Condensation
A. Hydrolysis. This breaks the peptide bond and forms amino acids. Peptide bonds can be called amide reaction, dehydration, dehydrolysis, or condensation
When two amino acids are condense into one, why is the use of ATP necessary? Is ATP always required?
Yes, ATP is always required because two individual amino acids are much more stable and therefore more thermodynamically stable that its products. Therefore the use of ATP is required to overcome this.
True or false: Because the dehydration of 2 amino acids has a high activation energy, requirement of ATP is the only thing required for this process to occur.
False. An enzyme is used to catalyze and transfer this energy released from the ATP to the amino acid reaction. In this way, the catalyst lowers the activation for reactions and allows the reaction to occur at a faster rate.
If these products are unfavorable and substrates are more stable, then why do these bonds not spontaneously break inside the body?
Due to high activation energy (highlighted in ΔE, therefore not kinetically favorable) Body doesn’t have enough energy to break the peptide bonds spontaneously as well as body conditions of pH and temp doesn’t allow for this occur.
Therefore the forward reaction of the peptide formation is kinetically favorable and backwards is kinetically unfavorable
Upon reviewing some microscopic slides from your patient, you note there are some proteins that are in between the neuronal synapse. These proteins appear to be similar to normal functioning amyloid beta precursor proteins (membrane proteins) with some differences in beta sheets. Which interaction is not properly occuring?
Beta sheets are part of the secondary structure of protein folding and they are stabilized by hydrogen bonds (seen in α helix too) therefore H bonds are not occurring or occurring erroneously to produce these amyloids
A molecule held by amide bonds in a polypeptide bonds are called:
A. α particles
B. β particles
C. Residues
D. Amino Acids
C. Residues - These are the specific names for individual amino acids, but can be interchanged with amino acid
Compare and contrast the locations of a hydrogen bond in a α helix vs a beta sheet.
α helix: the carbonyl (C=O) of one of the amino acid is hydrogen bonded to the amino acid is hydrogen (NH) of an amino acids that is 4 residue away.
β Pleated Sheet: 2 or more segments of a polypeptide chain line up next to each other, forming a sheet like structure held together by hydrogen bonds
Name all the interactions seen within the tertiary structure of a protein. These interactions can be seen where?
H bonds, Van Der Waals, hydrophobic packing & Disulfide bridges
Which environmental factors affect the formation of disulfide bridges? What components of this environment allows this interaction to occur?
External space outside there are no antioxidants (seen within the internal portion of the cell). Therefore the outside is an oxidizing environment, a condition that is required for disulfide bridges to occur?
Antioxidants found within the interior of the cell has what effects to the protein?
Antioxidants prevent oxidation of molecules, therefore redox reactions are reversed without oxidation, cysteine residues are unable to create disulfide bridges.
Is a waterless environment an oxidizing environment?
Oxidizing environment refer to an environment having the ability to accept hydrogens or donate electrons, typically such as an oxygen rich environment. Without water, the environments tend to be antioxidizing
A multimeric protein tends to be name after how many subunit are present?
4 subunits within the protein:
Dimer - 2 subunits
Trimer - 3 subunits
Tetramer - 4 subunits
Are these peptide bonds single bonds or are they something else?
Peptide bonds are resonance stabilized, therefore the left is not the only lewis structure. Single vs double bond. This means that the actual structure of the molecule is neither one or the other, it is somewhere in between. Therefore the peptide bond has double character. Length of bond is somewhere in between, peptide can’t rotate like double bonds, and therefore the backbone in which the peptide bond is in lie in the same plane
Explain why the trans isomer predominates and not cis isomer in a polypeptide chain
Therefore the two alpha carbons next to each other are always pointing in opposite direction. This configuration is more thermodynamically favorable vs cis. Pointing away leads to no steric hinderance (bumping of atoms) or electrostatic repulsion (bumping of electrons) [these drive the energy of cis isomer up]
Compare and contrast the difference between phi and psi angles
Phi (φ) is the angle of rotation about the single bond bt the nitrogen and alpha carbon and the psi (ψ) angle is the angle of rotation about the single bind between the alpha carbon and the carbonyl atom.
Both are torsional angle and they allow the linear sequence to become a 3D structure
True/False Even as the amide bonds can’t rotate, the 3 D structure of the protein can still exist as all psi and phi angles are possible to achieve this.
False Not all Psi (φ) and Phi (ψ) angles are possible due to steric hindrance. Therefore there is a limited number or rotations, therefore the polymer has to go through a less number of rotations to reach its final structure
Within an alpha helix, describe the location of the backbone and r groups in relation to one another.
Backbone is internal and R groups point externally
Usage of the word, screw sense, to describe folding of amino polypeptides is the same as A. Left Hand Rotation B. Right hand Rotation C. Counter clockwise D. DNA Helix
Right Hand Rotation, or clockwise rotation, describes the rotation of the helix about an axis
Why do alpha helices tend to be present in higher numbers of right hand rotations compared to left hand rotations?
Left hand helices are counter clockwise rotations about and axis and are less stable than due to the increase in hindrance between the R groups. Therefore it requires more energy to sustain this conformation and is less stable than the Right Hand helix
True or False. Within an Alpha helix, a hydrogen residue can be seen hydrogen bonding with another residue 4 amino acids away from it.
True. (draw out diagram) this structure lines the residues closest to one another to establish the H bonds
Compare and Contrast antiparallel and parallel beta sheets seen within the secondary structure of protein `
Antiparallel sheets are stacked on top of one another and but point in opposite directions. NH and CO of an amino acid on one strand interacts the opposing strand. The turn of the polypeptide chain can be a beta turn but can be any other turns as well. Once it takes place, it’s extension in the other direction lines up the amides of one aa and the carboxy of another.
Parallel sheets stacked on top of one another and point in the same direction. In this case, one amino acid interacts with two different amino acids from the opposite strand in order to fully H bond (see in diagram)
Adjacent strands run in the same direction
What are the factors and interactions that create the tertiary structure?
Factor - Hydrophobic effect - bec majority of pro fold in an aqueous solution (this is the dominant interaction) Water will cause nonpolar molecules to aggregate to form in an attempt to move away. This formation is thermodynamically stable
Others: Ionic, van der waals
True or False, Beta Turns occur every 4 residues
False, these hydrogen bonds occur every 3 residues.
True or False. All secondary structures are stabilized by hydrogen bonds
True, this include, Alpha Helices, Beta sheets, and beta Turns
What interactions can be seen within the hydrophobic core of a protein?
London dispersion forces AKA Van Der Waals - these exist the instantaneous dipole moments on the nonpolar.
True or False - The core of a protein is held by very weak interactions such as Van Der Waals, therefore the core itself is loosely held together.
False, though indv intramolecular interactions are very weak, many Van Der Waals/London Dispersions and hydrophobic effect can lead to a very strong adhesive core
True or False: Cystine and Cysteine are variations in spelling of the same molecule.
False: Cystines - when two cysteine loses their H and forms a cross link vs cysteine - a residue
Within a 3 D protein, you are able to visualize the interaction between a lysine and aspartate. What type of interaction is this? At what level of the protein is it stabilizing?
This is an ionic bond => In pH Lysine = full positive and aspartate = full negative => ionic bond. This stabilizes the tertiary structure.
In assessing a hemoglobin, you see interactions of an O from a carboxyl group from a subunit with the water molecule on the surface of the molecule. What type of interaction is this? What level of the protein is it stabilizing?
Hydrogen bond and stabilizes the tertiary structure
Myoglobin, like Hemoglobin, carries oxygen inside our muscles. Because Hemoglobin has a quaternary structure, myoglobin must also have a quaternary structure as proteins of the same function have similar structure
Not all proteins have a quaternary structure. Myoglobin only contains a tertiary structure
In assessing a Sodium channel, you see a disulfide bridge between two subunits within the membrane. What type of molecules achieve this? What structure of the protein does it stabilize?
2 Cysteines from different subunits achieve this after both are oxidized. This interaction stabilizes the quaternary structure of the transmembrane protein
What is the dominant type of interaction seen in quaternary structures of proteins?
Noncovalent interactions. Occasionally, you’ll see covalent bonds such as disulfide bridges
Alpha Keratin’s two subunits:
A. Consist of 2 beta sheets noncovalently bonded
B. Create a right handed coiled named an alpha coiled coil
C. Created a left handed coil named an alpha coiled coil
D. Consist of 2 alpha helices connected by beta turns
C. a dimer held by covalent (ionic bonds, hydrogen bonds) and non covalent interactions (London dispersions and disulfide bridges)
What is the effect of increasing or decreasing disulfide bridges within a protein?
Increasing disulfide bridges creates a more rigid structure allowing the protein to become stronger and decreasing them would decrease stability
Proteins can be categorized in many ways, one main way is to differentiate them as globular and fibrous proteins. Compare and contrast globular and fibrous proteins
Fibrous proteins are long structured and functions in providing structure to the cell. Ex: Intermediate filaments
Globular proteins are more spherical proteins that have a wide range of functions. Ex: Insulin - hormone
In assessing hemoglobin, how does the subunits of the protein affect the number of oxygen it is able to hold?
Each subunit of the Hemoglobin contains a prosthetic group called a heme that allows it to hold exactly one O2 therefore with 4 subunits, a hemoglobin is able to hold 4 oxygen molecules
What type of interaction between a heme group and an oxygen group allows the heme to attach the O2 to it?
Oxidation reduction reaction
Define denaturation of a protein.
Denature - Pro that have become unfolded and therefore inactive
How does the different 4 levels of protein structure help understand the conformational stability of a protein?
A protein is ONLY functional when they are in their proper conformation
True or False A protein is only active when they are in their proper conformation
True, any changes would denature it or cause misfolding which still leads to inactivity
Along with the 4 different levels of protein structure, what else helps with the understanding of conformational stability?
Solvation Shell - a layer of solvent surrounding the protein ex water. The water molecules are stabilizing the positively charged molecules seen on the surface of the protein. Therefore the environment determines the stability of a protein as well
What factors contribute to the denaturation of a protein?
Temperature (destroys 2 - 4 structures of a proteins)
pH destroys 3 and 4 structures
Chemicals destroys H bonds 2 - 4 bonds
Enzymes destroys 1 but because primary contributes to overall structure, it affects all levels
In cooking an egg for breakfast, you are increasing temperature to protein. What structures of the protein are you denaturing in this method?
2 - 4
As you add vinegar, an acid, to an egg, you can see the separation of it as a whole. What structures of the protein are you denaturing in this process?
Because ionic bonds (seen through acid and base interactions) are seen in stabilizing tertiary and quaternary structures, these are the structures that are breaking with the addition of acid
A protease released from the pancreas, digest proteins. What structure of the protein is this enzyme denaturing?
The goal of the enzyme is to disrupt the primary, however, because the primary determines the overall structure of the protein, all other structures are disrupted as a result of primary structure disruption
In Christian Anfinsen’s experiments to understand the primary sequence of proteins, he used urea and beta mercaptoethanol. What protein interactions are disrupted and at which levels?
Urea - breaks noncovalent bonds of the secondary and tertiary structures of a protein
Beta mercaptoethanol - breaks the noncovalent bonds, specifically disulfide bonds, of tertiary structure
The Native conformation of a protein is:
A. The denatured conformation of a protein
B. The proper conformation of a protein
C. The inactive state of a protein
D. The secondary structure of a protein
The proper conformation of a protein. The native structure of an enzyme describes the biologically active structure of the enzyme
What is Anfinsen’s goal in experimenting with ribonuclease?
Anfinsen wanted to destroy the secondary and tertiary structure of proteins and then see which conditions are needed to reform the structure.
In Anfinsen’s experiments, he adds urea and beta mercaptoethanol with ribonuclease, causing denaturation of the protein. After he filters the agents out, what results did he get? What do these results say overall?
After removing the agents, he found the protein had completely reformed. With nothing other than the primary structure present, he concluded that the primary structure is the only thing necessary to form the secondary and tertiary structure
In Anfinsen’s experiment, after denaturing ribonuclease, he decides to remove one agent at a time, starting with Beta-mercaptoethanol first. Then after a period of time, he removes the urea. After some time, the denatured polypeptide has reformed, but this time the disulfide bonds are in improper places. Explain why the results are improper?
Primary structure determines the interactions seen in the secondary structure and the secondary structure determines the tertiary structure. Beta mercaptoethanol denatures the tertiary disulfide bridges only Urea breaks noncovalent bonds in both the secondary and tertiary structure. Because only Beta-mercaptoethanol is removed, the secondary structure is unformed. Therefore there is no guidelines for the tertiary structure to form, however it will still occur, resulting in a random 3 D misfolded protein.
In Anfinsen’s experiment after he has created the misfolded ribonuclease, he added a small amount of beta-mercaptoethanol and then removes the agent again. What are the expected results now?
The beta-mercaptoethanol will denature the mismatched disulfide bridges resulting in only the linear polypeptide. Once this has happened, primary sequence will entail how the secondary structure to fold and this will inturn tell how the tertiary structure will fold. The ultimate result will be a normal protein ribonuclease will be formed at the end of the experiment
What property of a protein determines the function of the protein?
The 3D structure (usually tertiary, but quaternary structure as well)
In individuals with Crites Vl Jakob’s Disease, collections of amyloids or prions leads to what?
As prions grow and starts forming more aggregates, it causes cellular death. Overtime, the brain is filled with holes or it looks spongy due to losses of nuclei
In normal human bodies, misfolded proteins undergo…
They are either recycled or refolded into their proper conformation
Why is the body unable to recycle or refold prions?
Prions, aggregates of misfolded proteins, are not able to be refolded, because these aggregations are no soluble in water/body, a necessary condition to be recycled and destroyed.
PRP is a normal protein in the body and under certain conditions when it is misfolded, it is formed into PRPSC. How the structure of the protein change as it goes from its native to denatured state.
The predominant alpha helices are swapped with beta plated sheets
What property of beta pleated sheets allow them to be the center of amyloid aggregations?
Their linear stacked structure gives it the tendency to bind to other similar pleated sheets through hydrogen bonds
True/False - The unknown mechanism of amyloids is its ability to mysteriously transform normally folded proteins into Beta pleated sheets.
True. Once the normal protein converts, it is added onto the aggregation, increasing the size of the amyloid/prion
In 1996, 10 people contracted the Bovine Spongiform Encephalopathy after the consumption of diseased cow. What about prions made this possible?
Prions, the source of mad cow’s disease, has the ability to not just infect within species like bacteria and viruses, but it can also jump from species to species as well.
What are the two methods for synthesizing alpha amino acids?
Gabriel and Strecker Synthesis
In a lab, you are given the task to create an amino acid starting with only the following molecule (draw out molecule) What is the next step you need to take? What is the final step of this reaction before the alpha amino acid can be formed?
The first step is to add an electronegative alkyl group R-X such as Cl - CH3 this step allows the n-pthalmidomalonic molecule to be alkylated. The last step the reaction is to heat the substrate (the hydrolyzed substrate) to cause the carboxylic acid to leave (decarboxylating the hydrolyzed molecule)
In the process of making an alpha amino acid, you take a lunch break and come back and find this molecule. (draw molecule out) What did you add into the solution before you decided to take a lunch break? What is your next step?
The last step you performed was addition of a base along with an alkyl group. The next step you should perform is hydrolysis of the alkylated molecule to give you a molecule with two carboxylic acid
Instructed to make an amino acid, you find yourself staring at only a ketone as your starting molecule. What other agents do you need to add?
NH3 and KCN. NH3 is added to the ketone in acid as the first step to produce an imine (draw out) and KCN is used in the second step with acid to attack the carbon of the imine to produce an alpha amino nitrile.
You’ve made the alpha amino acid as you were instructed to! However, you need to document the steps and you don’t quite remember the last step since this alpha amino acid was made a week ago. You ask one of the lab assistants about what method is used and they tell you the only method they use in this lab is the Strecker method. What was the last method? What was the molecule before you finally created the amino acid?
Alpha Amino Nitrile - add acid to it => Amino acid by replacing the cyanide with a COOH and protonating the NH2
In the Gabriel Synthesis, the only starting molecule is the n-pthalimidomalonic ester. However in the Strecker synthesis, instead of Ketone, what other molecule can be used instead?
A. Ester
B. Carboxylic Acid
C. Aldehyde
D. Ether
C. Aldehyde
An amino acid has 3 pkas. What is the appropriate PI for this molecule?
Depending if the R group is an acidic or a basic group, you need to take the average of the pKa of the R group and (Depending if the R group is an acidic or a basic group) the pka of the carbonyl or the amino group respectively.
http://www.chem.ucalgary.ca/
What mnemonic can you use to remember basic amino acids?
Mean girls are basic: Regina, Karen, gretchen and cady Heron
R, K, H => Arginine, Lysine, and Histidine
