Chapter 1: Amino Acids, Peptides, and Proteins Flashcards
In a neutral solution, most amino acids exist as:
Zwitterions
At pH 7, the charge on a glutamic acid molecule is:
-1
Only two of the 20 amino acids have negative charges on their side change at physiological pH 7.4. Glutamic acid becomes glutamate at physiological pH of 7.4. The two of the 20 amino acids that have negative charges on their side chains at physiological pH is 7.4 or glutamic acid and a aspartic acid.
Glutamate is created from glutamine through a process called deamination, which is catalyzed by the mitochondrial enzyme glutaminase. Glutamic acid turns into glutamate at physiological pH of 7.4.
At pH 7, the charge on a glutamic acid molecule is:
-1
Only two of the 20 amino acids have negative charges on their side change at physiological pH 7.4. Glutamic acid becomes glutamate at physiological pH of 7.4. The two of the 20 amino acids that have negative charges on their side chains at physiological pH is 7.4 or glutamic acid and a aspartic acid.
Glutamate is created from glutamine through a process called deamination, which is catalyzed by the mitochondrial enzyme glutaminase. Glutamic acid turns into glutamate at physiological pH of 7.4.
What are amino acids? What is the alpha carbon of an amino acid? What is a side chain (R group) and why are they important?
Amino acids or molecules that contain two functional groups: an amino group (NH2) and a carboxyl group (COOH).
The alpha carbon of an amino acid is the central carbon of the amino acid. The alpha carbon has two other groups attached to it: a hydrogen atom and a side chain.
The side chain is specific to each amino acid.
Why are R groups of amino acids significant?
Side chains of amino acids determine their chemical properties.
What are proteinogenic AA?
Proteinogenic AA are those of 20 alpha AA (those which the R group is attached to the alpha carbon of AA) encoded by the human genetic code.
Which AA is not chiral or stereogenic?
Glycine is achiral as it has H as its R group.
All chiral AA used in eukaryotes are what kind of AA? Is there a technical exception to this?
Hint: stereochemistry.
All chiral AA used in eukaryotes are L-AA.
The technical exception to this is Glycine (Gly, G) as it has two hydrogen attached to its alpha carbon (along with the carboxyl and amino group) and is therefor achiral.
Draw L and R generic AA using a Fischer projection.
Of all the proteinogenic AA, all of them are chiral expect for glycine. All of them are also (S) configuration except for one. Which one? Why?
Cysteine is R configuration, all of the other are (S).
This is due to the R group (CH2SH) having a priority over carboxyl group (COOH).
Am I expected to know the structures, names, and three letter and one letter abbreviations for the 20 proteinogenic amino acids?
Yep.
How many nonpolar nonaromatic proteinogenc amino acids are there? What are they? Whats a simple way to remember them?
There are seven.
One of them is glycine (GLY, G… H side chain, smallest AA)
Four of them: alanine (ALA, A), valine (VAL, V) , leucine (LEU, L), and isoleucine (ILE, I) have alkyl side chains containing one to four carbons.
Methionine (MET, M) is only one of two proteinogenic AA that has a sulfur atom in its side chain (nevertheless considered non polar like the others in this group)
Proline (PRO, P) is unique because it forms a cyclic AA. Pay attention to this: all the other amino acids amino group is attached ONLY to the alpha carbon.
How many aromatic side chain proteinogenic amino acids are there? Whats a good way to remember them?
There are three.
Tryptophan (TRP, W because when you draw it it sort of looks like a W sort of kind of a little bit)
Phenylalanine (PHE, F because phonetic similarity to Ph in the name)
Tyrosine (TYR, Y because it’s a Y)
How many polar side chain proteinogenic amino acids are there? Whats a good way to remember them?
There are five. The side chains of these are polar but not aromatic.
Serine (SER, S) and Threonine (THR, T) both have -OH (alcohol) groups in their side chains, making them highly polar and able to participate in H bonding.
Asparagine (ASN, N asparagi-N-e) and Glutamine (GLN, Q because Q) have amide (CONH2) side chains.
Cysteine (CYS, C) has a thiol (SH) group in its side chain.
How many negatively charged ACIDIC proteinogenic amino acids are there? Whats a good way to remember them? Why do we hear them more often in their anion names instead of their acid names?
There are two.
ONLY TWO OF THE 20 HAVE NEGATIVE CHARGES AT PHYSIOLOGICAL PH OF 7.4:
Aspartic acid (ASP, D because aspar-D-ic acid or aspartate when it’s negatively charged)
Glutamic acid (GLU, E because it follows D for aspartic acid, called glutamate when it’s negatively charged.
The reason we hear aspartate and glutamate instead of aspartic acid or glutamic acid is because most acids in cells exist in the deprotonated form. This also applies to molecules other than amino acids (for example malate instead of malic acid).
How many positively charged BASIC side chain proteinogenic amino acids are there? Whats a good way to remember them?
There are three.
Arginine (ARG, R because a-RRR-ginine) has three nitrogen atoms in its side chain in which the positive charge is delocalized over all three N atoms.
Lysine (LYS, K because alphabetically close to L for leucine) has a terminal primary amino group.
Histidine (HIS, H) has an aromatic ring with two nitrogen atoms (called imidazole). The pKa is about 6, causing protonation of one of the N atoms (and not the other) at physiological pH of 7.4.
Where will you find strongly hydrophobic amino acids in a protein?
The surface of a protein tends to be rich in amino acids with charged side chains. Strongly hydrophobic amino acids tend to be found in the interior of proteins.
What amino acids (generally and specifically) are strongly hydrophobic (5 of them)? Where will you typically find them in proteins? Draw em.
The amino acids with long alkyl side chains are considered strongly hydrophobic.
alanine (Ala, A)
leucine (Leu, L)
valine (Val, V)
phenylalanine (Phe, F)
isoleucine (Ile, I)
Because they are strongly hydrophobic, we will find alanine, leucine, valine, isoleucine, and phenylalanine in the interior of proteins, away from polar stuff like water and stuff.
What amino acids (generally and specifically) are strongly hydrophilic (7 of them)? Where will you typically find them in proteins? Draw em.
The seven AA considered strongly hydrophilic are:
positively charged histidine (His, H), arginine (Arg, R), lysine (Lys, K)
negatively charged glutamate (Glu, E), aspartate (Asp, D)
Amides asparagine (Asn, N) and glutamine (Gln, Q)
The surface of protein tends to be rich in amino acids with charged side chains.
There are 5 hydrophilic AA and 7 hydrophobic AA. This means there are 8 that are not particularly hydrophobic nor hydrophilic. Name em draw em label them with both abbreviations. Is there anything particularly unique about about any of them?
Cysteine (Cys, C) and methionine are the only two with sulphur.
Proline (Pro, P) forms - cyclic AA where the amino group and the side chain are attached to the alpha carbon.
Serine (Ser, S) and threonine (Thr, T) have alcohol groups on their side chain.
Tryptophan (Trp, W) has two rings and looks like a W.
Glycine (Gly, G) is achiral as its side chain is H and therefore has 2 H attached to the alpha carbon.
What two AA contain sulphur?
Cysteine (Cys, C) and methionine (Met, M)
Draw and label all of the 20 proteinogenic AA sorted by nonpolar nonaromatic (7), aromatic (3), polar (5), negatively charged acidic (2), positively charged basic (3)
List the 20 AA by three and one word abbreviation.
MCAT concept check AA 1.1 page 15 question 1
What are the four groups attached to the central carbon (alpha carbon) of a proteinogenic amino acid?
MCAT concept check AA 1.1 page 15 question 2
MCAT concept check AA 1.1 page 15 question 3
MCAT concept check AA 1.1 page 15 question 5
What is an amphoteric species?
Amphoteric species, like AA, can either accept a proton or donate a proton depending on the pH of the environment.
They can act as a base or an acid.
What will an ionizable group tend to do when exposed to low or high pH?
Ionizable groups tend to gain protons under acidic conditions, and lose them under basic conditions.
In general:
low pH = protonated
high pH = deprotonated
What is the pKa of a group?
The pKa of a group is the pH at which half of the molecules of that species are deprotonated.
Relate pH and pKa and what happens when pH does not equal pKa.
pKa is when half of the molecules are protonated and the other half is deprotonated.
When pH is less than pKa, majority of species will be protonated.
When pH is greater than pKa, majority of species will be deprotonated.
How many pKa values do amino acids have? Why?
They all have at least two as they all have at least two groups that can be deprotonated.
The first pKa is for the COOH group and it around pKa=2
The second pKa is most often for the amino group with pKa between 9 and 10.
What is the pKa for the COOH group of an AA? For the amino group?
COOH group pKa is 2
Amino group pKa is 9-10
At very low pH, what charge will an AA have? Use Gly G as an example.
At very low pH (acidic) there are plenty of protons in solution and will leave the amino group protonated and the COOH group will remain protonated.
Therefor the charge of an AA in very low pH (around 1) will be positive due to the protection of the amino group.
What is a zwitterion? At what pH will most amino acids exist as zwitterions?
A zwitterion is a dipolar ion with an overall net charge of zero.
At physiological pH of 7.4, we will find the COOH group deprotonated and the amino group protonated as pH is greater than pKa of COOH and less than pKa of amino group.
At very high pH, what charge will an AA have? Use Gly G as an example.
At high pH (basic, pH of 10.5 and up) the COOH group is already deprotonated and the pH is greater than pKa of amino group and therefor deprotonated as well and the AA will gain a negative charge.
Charge of AA in high acidic values (pH=1)
Charge of AA in alkaline values (pH=11)
At very high acidic pH, AA tend to be positive.
At very alkaline pH, AA tend to be negatively charged.
At what pH will a solution act as a buffer? Draw a titration curve of Gly.
When pH of solution is approximately equal to the pKa of solute, the solution will act as a buffer that resist pH change.
The pKa for glycine is 2.3 and 9.6. When will it be positively charged? Zwitterion (isoelectric point)? Negatively charged?
It will be negatively charged when the pH is around 2.3. Isoelectric point will be around 6. Negatively charged when the pH is greater than 9.6.
Remember that a buffer will occur in solution when pH approximately equals the pKa. Amino acids are prime candidates for titrations due so their property of being polyprotic amphoteric species.
What is the isoelectric point? Equation?
The isoelectric point is the pH at which the molecule is electrically neutral.
pH=pI halfway between the two pKa of a neutral AA.
How do we calculate the pI of an AA with acidic side chains?
Recalling that the titration of an AA with charged side chain, such as lysine or glutamic acid, has an extra step but works along the same principles.
How do we calculate the pI of an AA with basic side chains?
In general, what will be the pI value of acidic side chain AA? Basic?
Amino acids with acidic side chains have relatively low isoelectric points (well below 6).
AA basic side chains will have relatively high isoelectric values (well above 6).
MCAT concept check acid base chemistry of AA page 20 question 1
Positive
Neutral (zwitterion)
Negative
MCAT concept check acid base chemistry of AA page 20 question 2
What are peptides? Dipeptides, tripeptides, oligopeptides, polypeptides?
Why is peptide bond formation known as condensation or dehydration?
The formation of the bond results in the removal of a water molecule.
Which way is a peptide drawn (regarding terminus)?
From n terminus (amino end) to c terminus (carboxy ends). This is the same order that they are synthesized by ribosomes (translation).
Why is the backbone of a protein rigid? How can they have resonance structures?
For the same reason: Because of the delocalizable pi electrons in the carbonyl and lone pair on the amino nitrogen of the amide group.
It’s worthy to note that all of the other bonds in the backbone are sigma bonds and therefor are not restricted or rigid.
Name two pancreatic hydrolytic enzymes.
Trypsin and chymotrypsin.
How do hydrolytic enzymes work?
They catalyze hydrolysis by breaking apart the amide bond by adding a hydrogen atom to the amide nitrogen and an OH group to the carbonyl carbon.
MCAT concept check peptide bind formation and hydrolysis question 1
MCAT concept check peptide bind formation and hydrolysis question 2
What molecule is released during formation of a peptide bond?
Water
MCAT concept check peptide bind formation and hydrolysis question 3
What are the four levels of protein structure?
Primary, secondary, tertiary, and quaternary.
What is the primary structure of a protein?
It is the linear arrangement of AA codes in the organisms DNA. The sequence of AA, listed from the N to the C terminus.
What is the secondary structure of a protein?
A protein secondary structure is the local structure of neighboring amino acids. The two main secondary structures are alpha helix and beta pleated sheet, both resulting from hydrogen bonding.
What is an alpha helix? What causes it? What is a good example of a protein with a helical shape?
Alpha helices are one of two kinds of secondary structures of amino acids. It is a rod like structure in which the peptide chain coils clockwise around the central axis. The helix is stabilized by intermolecular hydrogen bonds between carbon oxygen atoms, and an amide hydrogen atom four residues down the chain.
Keratin has an alpha helical shape. Keratin is a fibrous structural protein found in skin, hair, and fingernails.
What is a beta pleated sheet?
Beta pleated is one of two secondary structures of an AA. In a beta pleated sheet, which can be parallel or anti-parallel, the peptide chains lie alongside one another forming rows or strands held together by hydrogen bonds between carbon oxygen atoms on one chain and amide hydrogen atoms in the adjacent chain.
Where is proline often found? Recall why proline is unique.
Proline has a rigid cyclic structure.
Proline will introduce a kink in the peptide chain when it is found in the middle of an alpha helix. Proline residues are rarely found in alpha helices, except in helices that cross the cell membrane.
Proline is rarely found in the middle of pleated sheets. Proline is often found in the turns between the chains of a pleated sheet, and is often found as the residue at the start of an alpha helix.
MCAT concept check primary and secondary protein structure 1.4 question 1
MCAT concept check primary and secondary protein structure 1.4 question 2
What role does proline serve in secondary structure?
Proline’s rigid structure causes it to introduce kinks in alpha helices or create turns and beta pleated sheets.
MCAT concept check primary and secondary protein structure 1.4 question 3
Describe the key structural feature of alpha helix and beta pleated sheet.
Proteins can be broadly divided into two gross shapes. What are they?
Fibrous proteins such as collagen that have structures that resemble sheets or long strands.
Globular protein such as myoglobin that tend to be spherical.
These shapes are caused by tertiary and quaternary protein structures, both of which are the result of protein folding.
What is tertiary protein shape? What causes this?
A proteins tertiary structure is its three-dimensional shape.
The tertiary structure of a protein is primarily the result of moving hydrophobic amino acid side chains into the interior of the protein, which reduces those amino acid proximity to water.
What is a disulfide bond? What amino acid is known for forming disulfide bonds? Can methionine form disulfide bonds?
Disulfide bonds form when two cysteine molecules become oxidized to form cystine. Disulfide bonds create loops in the protein chain and determine how wavy or curly human hair is. The more disulfide bonds, the curlier it is.
Note that forming a disulfide bond requires the loss of two protons and two electrons (oxidation)
What is denaturation?
If a protein loses its tertiary structure, a process commonly called denaturation, it loses its function.
What is a quaternary structure of protein? Do all proteins have quaternary structure? What’s a classic example of biologically relevant quaternary structure of a protein?
Quaternary structures only exist for proteins that contain more than one polypeptide chain. Quaternary structure is an aggregate of smaller globular, peptides, or subunits, and represent the functional form of the protein.
Hemoglobin consists of four distinct subunits, each of which will bind one oxygen molecule. Immunoglobulin G (IgG) antibodies also contain a total of four subunits each.
What are conjugated proteins? Give three general examples of conjugated proteins.
Lipoproteins, glycoproteins, nucleoproteins
Conjugated proteins derive part of their function from covalently attach molecules called prosthetic groups.
Proteins with lipid prosthetic groups are lipoproteins
Proteins with carbohydrates prosthetic groups are glycoproteins
Proteins with nucleic acid prosthetic groups are nucleoproteins
MCAT concept check tertiary and quaternary structure of proteins 1.5 question 1
What is denaturation? What are three main causes of denaturation?
Denaturation is the process in which a protein loses its three dimensional structure. Unfolded proteins cannot catalyze reactions.
The three main causes of denaturation are heat, pH, solutes.
MCAT concept check denaturation 1.6 question 1
Why are proteins denatured by heat and solutes?
Heat denatures proteins by increasing their average kinetic energy, thus disrupting hydrophobic interactions.
Solids denature proteins by disrupting elements of secondary, tertiary, and quaternary structure.
MCAT mastery AA, peptides, proteins, page 4 question 1
MCAT mastery AA, peptides, proteins, page 4 question 2
MCAT mastery AA, peptides, proteins, page 4 question 3
MCAT mastery AA, peptides, proteins, page 4 question 4
MCAT mastery AA, peptides, proteins, page 4 question 5
MCAT mastery AA, peptides, proteins, page 4 question 6
MCAT mastery AA, peptides, proteins, page 4 question 7
MCAT mastery AA, peptides, proteins, page 4 question 8
MCAT mastery AA, peptides, proteins, page 4 question 9
MCAT mastery AA, peptides, proteins, page 4 question 10
Which two amino acids of the 20 amino acids have a chiral carbon on their side chain?
Only two of the 20 amino acids have a chiral carbon in their side chain: threonine (Thr T) and isoleucine (Ile I)
MCAT mastery AA, peptides, proteins, page 4 question 11
MCAT mastery AA, peptides, proteins, page 4 question 12
MCAT mastery AA, peptides, proteins, page 4 question 13
MCAT mastery AA, peptides, proteins, page 4 question 14
MCAT mastery AA, peptides, proteins, page 4 question 15
What three AA are found in high concentration in collagen?
