Proteins for the MCAT
Which amino acid category does D belong to?
*Aspartic acid Acidic amino acid (hydrophilic, negatively charged at physiological pH)
Which amino acid category does Glu belong to?
*Glutamic acid Acidic amino acid (hydrophilic, negatively charged at physiological pH)
Name all 5 aliphatic amino acids
*VAIL G 1. Valine (Val, V) 2. Alanine (Ala, A) 3. Isoleucine (Ile, I) 4. Leucine (Leu, L) 5. Glycine (Gly, G)
What level of protein structure is responsible for the formation of multimers?
*multimer: more than 4 polypeptide chains linked to form a functional protein Quaternary structure
If you preformed gel electrophoresis at a pH of 6 to separate alanine, glutamic acid and arginine, which end would each amino acid migrate towards and why?
-Alanine would be neutral so it wouldn't migrate -glutamic acid would be negative so it would migrate towards the cathode (+) end -Arginine would be positive so it would migrate towards the anode (-) end
What are 2 ways to break a peptide bond?
1. Acid/heat hydrolysis (not specific) 2. Proteolysis (specific cleavage by proteases between specific residues)
Name the 7 categories of amino acids used in this class
1. Aliphatic 2. Sulfur-containing 3. Aromatic 4. Imino acid 5. Neutral polar 6. Acidic 7. Basic
Name 2 acidic amino acids
1. Aspartic acid (Asp, D) 2. Glutamic acid (Glu, E)
What 2 ways of denaturing a protein will not affect primary and secondary structures?
1. Changing the pH 2. Adding salts Both of these will affect the interactions between acidic and basic amino acids [ionic salt bridges] --> affects tertiary and quaternary structure
Name 2 sulfur containing amino acids
1. Cysteine (Cys, C)- can form disulfide bonds with other cysteine residues 2. Methionine (Met, M)-cannot form disulfide bonds
What 2 things are important for protein conformational stability?
1. Fidelity to the protein's intended primary, secondary, tertiary and quaternary structure 2. The formation of a solvent shell in aqueous solutions
Name 3 basic amino acids
1. Histidine (His, H) 2. Lysine (Lys, K) 3. Arginine (Arg, R)
Which two amino acids are known for their reactivity and often found within the active/ catalytic sites of enzymes?
1. Histidine (basic amino acid) 2. Cysteine (sulfur-containing amino acid)
What 2 ways of denaturing a protein will affect secondary, tertiary, and quaternary structure but not primary structure?
1. Increasing temperature (amino acids gain energy and bonds vibrate and stretch until all non-covalent bonds are destroyed) 2. Adding chemical detergents (disrupt hydrogen bonding)
Name 3 aromatic amino acids
1. Phenylalanine (Phe, F) 2. Tyrosine (Tyr, Y)- slightly hydrophilic because aromatic ring bears a hydroxyl group 3. Tryptophan (Trp, W)
Describe the charge of an amino acid under these 3 conditions: 1. pH below its pI 2. pH equal to its pI 3. pH above its pI
1. Positive (both the acidic and the basic groups are protonated [acidic groups: neutral, basic groups: positive]) 2. Neutral (thats the definition of pI/ isoelectric point) 3. Negative (both the acidic and basic groups are deprotonated [acidic groups: negative, basic groups: neutral])
For most amino acids, L configuration means [1. Blank] stereochemistry and D configuration means [2. Blank] stereochemistry
1. S 2. R
Name 4 neutral, polar amino acids
1. Serine (Ser, S) 2. Threoine (Thr, T) 3. Asparagine (Asn, N) 4. Glutamine (Glu, Q)
Quaternary structure 1. What is it? 2. What types of bonds are important to this structure?
1. Side-chain (R-group) interactions between different polypeptide chains 2. The same types of bonds that are important in tertiary structure (Salt bridges (ionic), polar to polar, non-polar to non-polar and disulfide bridges)
Secondary structure 1. What is it? 2. What types of bonds are important to this structure? 3. Examples (2)
1. The interactions between backbone carboxylic acid and amino groups 2. Hydrogen bonds 3. Alpha helix, beta pleated sheet
Tertiary structure 1. What is it? 2. What types of bonds are important to this structure?
1. The interactions of R groups in a single polypeptide chain 2. Salt bridges (ionic), polar to polar, non-polar to non-polar and disulfide bridges
Primary structure 1. What is it? 2. What types of bonds are important to this structure?
1. The sequence of amino acid residues (N to C) 2. Peptide bonds
How many amino acids are encoded in DNA triplets (i.e. are naturally occurring)?
20
An amino acid that is not acidic or basic will have a pI (isoelectric point) close to:
6
What is the pI of histidine? Why is this important?
7.6 7.6 is extremely close to physiological pH (~7.4). That means histidine can be found in both protonated (charged) and deprotonated (neutral) states in the body
How many essential amino acids are there?
9
Zwitterion
A molecule that contains charges, but is neutral overall
A
Alanine
Ala
Alanine
Which amino acid category does alanine belong to?
Aliphatic amino acid (hydrophobic, hydrocarbon side chain)
Which amino acid category does glycine belong to?
Aliphatic amino acid (hydrophobic, hydrocarbon side chain)
Which amino acid category does isoleucine belong to?
Aliphatic amino acid (hydrophobic, hydrocarbon side chain)
Which amino acid category does leucine belong to?
Aliphatic amino acid (hydrophobic, hydrocarbon side chain)
Which amino acid category does valine belong to?
Aliphatic amino acid (hydrophobic, hydrocarbon side chain)
Describe the structure of acidic amino acids
Amino acids with hydrophilic side chains containing carboxylic groups that are negatively charged (deprotonated) at physiological pH.
Describe the structure of neutral, polar amino acids
Amino acids with hydrophilic side chains that are polar but not charged at physiological pH. Neutral amino acid side chains (R groups) contain either hydroxyl (OH) or amide groups
Describe the structure of basic amino acids
Amino acids with hydrophilic side chains that are positively charged (protonated) at physiological pH
Describe the structure of aliphatic amino acids
Amino acids with hydrophobic hydrocarbon side chains (R groups)
Describe the structure of aromatic amino acids
Amino acids with large/bulky R groups containing aromatic rings. Aromatic amino acids are generally hydrophobic (exception: tyrosine) and are found at the cores of folded proteins
Arg
Arginine
R
Arginine
Which amino acid category does phenylalanine belong to?
Aromatic amino acid (large/ bulky, hydrophobic)
Which amino acid category does tyrosine belong to?
Aromatic amino acid (large/bulky aromatic R group with conjugated hydroxyl group; slightly hydrophilic)
Which amino acid category does tryptophan belong to?
Aromatic amino acid (large/bulky, hydrophobic R group)
Asn
Asparagine
N
Asparagine
Asp
Aspartic acid
D
Aspartic acid
Polypeptide chains are written: A. C (carboxyl) to N (amino) terminus B. N (amino) to C (carboxyl) terminus C. There is no specified order
B. N (amino) to C (carboxyl) terminus
Which amino acid category does lysine belong to?
Basic amino acid (hydrophilic, positively charged at physiological pH)
Which amino acid category does histidine belong to?
Basic amino acid (hydrophilic, positively charged at physiological pH) -NOTE: Histidine's pKa is ~7. Histidine can therefor act as an acid or a base (~50% of histidine residues will be protonated at physiological pH)
Which amino acid category does arginine belong to?
Basic amino acid (hydrophilic; positively charged at physiological pH)
What amino acids are charged at physiological pH?
Basic and acid amino acids: Dr. Hek D: Aspartic acid R: Arginine H: histidine E: glutamic acid K: lysine
Describe the basic structure of all amino acids
Central (alpha) carbon bound to 1 hydrogen atom, 1 amino group (positively charged at physiological pH), 1 carboxyl group (negatively charged at physiological pH) and 1 R group or side chain.
C
Cysteine
Cys
Cysteine
Which amino acid can form disulfide bonds?
Cysteine
Which amino acid changes to a dimer in oxidizing environments?
Cysteine (cystine: the oxidized dimer of 2 cysteine amino acids)
Polypeptide bond formation is a type of [Blank] synthesis
Dehydration
How do proteins loose their function?
Denaturation
Amino acids are: A. Amphoteric B. Amphipathic C. Zwitterions D. None of the Above E. Just A and C F. A, B and C
E. Just A and C (amphoteric and zwitterions) Amphoteric: can act as an acid or base Amphipathic: having hydrophobic and hydrophilic regions (not true for all amino acids) Zwitterions: molecules with multiple charges that are neutral overall
L and D amino acids are:
Enantiomers
True or False: All of the charged amino acids are essential
False (out of the charged amino acids, only lysine and histidine are essential)
What type of laboratory amino acid synthesis reaction has the following starting materials: Potassium phthalimide ester and Diethyl bromonalonate
Gabriel Malonic Ester synthesis
What type of laboratory amino acid synthesis reaction requires the amino acid R-group to be added in the middle of the reaction using a Grignard reagent?
Gabriel Malonic Ester synthesis
E
Glutamic acid
Glu
Glutamic acid
Gln
Glutamine
Q
Glutamine
What type of amino acid resembles glutamic acid but has a NH2 group in place of a hydroxyl group (i.e. it has an amide rather than a carboxylic acid side chain)?
Glutamine (Glu,Q)
G
Glycine
Gly
Glycine
All amino acids are chiral except for:
Glycine (R group: H)
Which amino acid has a single hydrogen atom as its R group?
Glycine (simplest amino acid; not very hydrophobic)
Basic amino acids will have isoelectric points that are:
Greater than 6
H
Histidine
His
Histidine
Peptide bond cleavage is an example of what type of reaction?
Hydrolysis (insertion of H2O to break a bond)
What amino acid groups can be found on the exterior surfaces of proteins?
Hydrophilic groups (neutral polar, acidic, and basic amino acids) Note: Cysteine (sulfur-containing amino acid) behaves like a neutral, polar amino acid
Which groups of amino acids are found in the interior of proteins?
Hydrophobic groups (Aliphatic, Aromatic, and Imino amino acids) Note: Methionine (sulfur-containing amino acid) behaves like an aliphatic amino acid
Which amino acid category does proline belong to?
Imino acid (R group connects proline's alpha carbon and amino group, forming a cyclic structure)
I
Isoleucine
Ile
Isoleucine
What makes each amino acid unique?
Its side chain (R group)
What configuration do all amino acids have in the body?
L (in a fisher projection, the amino group is on the left, the COOH group is on top, the R group is on the bottom and the alpha hydrogen is on the right)
L
Leucine
Leu
Leucine
K
Lysine
Lys
Lysine
M
Methionine
Met
Methionine
At a pH of 7, would aspartic acid be positive, negative or neutral?
Negative pKa of carboxylic acid ~2 --> will be deprotonated and negative pKa of amino group ~9 --> will be protonated and positive pKa of R group with carboxylic acid ~3 --> will be deprotonated and negative
Which amino acid category does aspargine belong to?
Neutral, polar amino acid (hydrophilic)
Which amino acid category does glutamine belong to?
Neutral, polar amino acid (hydrophilic)
Which amino acid category does serine belong to?
Neutral, polar amino acid (hydrophilic)
Which amino acid category does threonine belong to?
Neutral, polar amino acid (hydrophilic)
Name the essential amino acids
PVT TIM HaLL Phenylalanine Valine Threonine Tryptophan Isoleucine Methionine Histidine Leucine Lysine
F
Phenylalanine
Phe
Phenylalanine
Polypeptides are synthesized in what direction? What does this mean?
Polypeptides are synthesized in the N to C direction. That means new amino acid residues are added onto the carboxyl end of the growing polypeptide chain
At a pH of 6, would lysine be positive, negative or neutral?
Positive pKa of carboxylic acid is ~2 --> will be deprotonated and negative pKa of amino group ~9 --> will be protonated and positive pKa of amide side chain ~10 --> will be protonated and positive
P
Proline
Pro
Proline
Which amino acid is actually classified as an imino acid?
Proline
What is one way to destroy all levels of protein structure?
Proteolytic cleavage with proteases
S
Serine
Ser
Serine
Acidic amino acids will have isoelectric points that are:
Significantly less than 6 (around 2 and 3)
What type of laboratory amino acid synthesis reaction has the R-group present from the beginning?
Strecker synthesis
What type of laboratory amino acid synthesis reaction involves cyanide preforming a nucleophilic attack on an imine (C=N) carbon?
Strecker synthesis
Which amino acid category does cysteine belong to?
Sulfur-containing -Cysteine behaves like a neutral, polar amino acid (hydrophilic)
Which amino acid category does methionine belong to?
Sulfur-containing -Methionine behaves like a hydrophobic aliphatic amino acid (S is not terminal and is thus non-reactive)
T
Threonine
Thr
Threonine
Trp
Tryptophan
W
Tryptophan
Tyr
Tyrosine
Y
Tyrosine
V
Valine
Val
Valine
Cysteine vs cystine
cysteine = *reduced* form of the a.a. (remember: the *e* is for *electrons*... which you still have in *reduced form*) cystine = *oxidized* form of the a.a.; 2 cysteine residues connected by a disulfide bridge (remember: the absence of the *e* means loss of *electrons*, which is what you face in *oxidation*)
The [blank] tells you the pH at which a functional group is deprotonated. For an acid, this deprotonation creates a negative charge. For a base, this deprotonation creates a neutral/ uncharged group
pKa
Is the nitrogen that is participating in a peptide bond sp2 or sp3 hybridized?
sp2 The peptide bond is resonance stabilized. The pi electrons in the carbonyl double bond can form a double bond between the carbon and nitrogen participating in the peptide bond
What levels of protein structure are affected by disulfide bridge formation?
tertiary and quaternary