Amino Acids, Peptides, and Proteins

**Amino Acids, Peptides, and Proteins**

Amino Acids Found in Proteins
 Amino acids contain two functional groups, an amino group (-NH2) and a carboxyl group
(-COOH) which are formed on a carboxylic acid.
o Alpha amino acids are those where both functional groups are attached to the
same carbon.
o Side chain/R group and hydrogen atom are also attached to alpha carbon.
 Side chain determines the properties of amino acids and its functions.
Terminology
 There are a variety of different types of amino acids, however the MCAT only focuses on
the 20 alpha-amino acids that are encoded by the human genetic code.
o Called the proteinogenic amino acids
Stereochemistry of Amino Acids
 Alpha carbon is usually a chiral center since it has four different groups attached to it.
o Thus most amino acids are optically active
 Glycine is the only exception since it has a hydrogen as its R group.
 All chiral amino acids are L-amino acids, which means that the amino group is drawn
on the left side for the Fischer projection.
o Translates to an (S) absolute configuration for almost all chiral amino acids.
 Cysteine is the only amino acid that has an L-amino acid configuration
but has an (R) absolute configuration. This is because the carboxyl group
is not the highest priority functional group.

Structures of the Amino Acids
Amino acids can be classified by the structure of their side chains.
Nonpolar, Nonaromatic Side Chains – 7 amino acids
 Glycine: has a single hydrogen bond as its side chain and is the smallest amino acid.
 Alanine, valine, leucine, and isoleucine: have alkyl side chains containing one to four
carbons
 Methionine: one of only two amino acids with a sulfur attached to it.
o Sulfur does not induce polarity since it has a methyl group attached to it.
 Proline: forms a cyclic amino acid. Amino nitrogen becomes a part of the side chain
through the formation of a five-membered ring.
o Ring places constraints on the flexibility of proline

,Aromatic Side Chains – 3 amino acids
 Tryptophan: largest and has a double ring system that contains a nitrogen atom
 Phenylalanine: smallest and has a benzyl side chain. Non polar.
 Tyrosine: -OH group is added to phenylalanine. Polar




Polar Side Chains – 5 amino acids
 Serine and threonine: have –OH groups which makes them highly polar.
 Asparagine and glutamine: amide side chains
o Amide Nitrogen’s do not gain or lose protons with changes in pH, so they do not
become charged
 This is the opposite of what amino group nitrogen’s do.
 Cysteine: thiol (-SH) group in its side chain. Since sulfur is larger and less electronegative
than oxygen, the S-H bond is weaker than the O-H bond and is thus more prone to
oxidation.




Negatively Charged (Acidic) Side Chains – 2 Amino acids
 Aspartic Acid (aspartate): deprotonated form of aspartic acid
 Glutamic acid (glutamate): deprotonated form of glutamic acid




Positively Charged (Basic) Side Chains – 3 amino acids
 All three have a positively charged nitrogen atom
 Lysine: terminal primary amino group
 Arginine: three nitrogen atoms in its side chain with the positive charge delocalized over
all three.
 Histidine: aromatic ring with two nitrogen atoms (ring is called imidazole)

,Hydrophobic and Hydrophilic Amino Acids
 Amino acids with long alkyl side chains – alanine, isoleucine, leucine, valine, and
phenylalanine – are strongly hydrophobic, and are thus more likely to be found in
the interior of proteins
 All amino acids with charged side chains – histidine, arginine, lysine, glutamate, and
aspartate – are hydrophilic
o So are the amides asparagine and glutamine
 Remaining amino acids are somewhere in the middle between being philic and phobic.
Amino Acid Abbreviations
 Expected to identify an amino acid by the name, three-letter abbreviation and one-
letter abbreviations




Acid-Base Chemistry of Amino Acids
 Amino acids are an amphoteric species since they have an acidic carboxyl group and a
basic amino group.
 Ionizable groups tend to gain protons under acidic conditions and lose them under
basic conditions.
o i.e. at low pH an ionizable group will be protonated

,  The pKa of a group is the pH at which half of the molecules of the species are
deprotonated or [HA]=[A-]
o If pH is lower than pKa then the majority of the species will be protonated.
Protonation and Deprotonation
 All amino acids have at least two pKa values.
o pKa1 is the pKa of the carboxyl group and is usually around 2
o pKa2 is the pKa of the amino group and is usually around 9-10
 If the amino acid has an ionizable side chain, then there will be three pKa values.
Positively Charged under Acidic Conditions
 At pH below 1, the pKa is far below that of the amino group, so the amino group is fully
protonated (-NH3+)
o Additionally, the carboxylic acid group is fully protonated (-COOH)
 At very acidic pH values, amino acids tend to be positively charged.
Zwitterions at Intermediate pH
 At pH of 7.4, carboxylic acid pKa has been moved past. As such, you will not find amino
acids with their carboxylate group protonated and the amino group unprotonated
o Amine group stays protonated since the pKa still is not high enough.
 Resulting molecule has both a positive charge and a negative charge, but is overall
neutral.
o These are called dipolar ions or zwitterions. These exist in water as internal salts.




Negatively Charged under Basic Conditions
 pKa of the amino group is below the pKa at higher pH’s>10, which means that the amino
group deprotonates to NH2
 So the molecules become negatively charged at high pH
Titration of Amino Acids
 The titration curve should look like a combination of two monoprotic acid curves or
three curves if the side chain is charged.
 Starting at low pH, the amino acid is fully protonated. As the pH approaches pKa1, the
solution begins acting like a buffer and this is characterized by a straight line on the
graph.
o When pH= pKa1, then [HA]=[A-]
 Isoelectric Point (pI): the pH at which the molecule is electrically neutral which means
that the amino acid exists exclusively in its zwitterion form.
o Can be calculated for neutral amino acids by the following:
pI𝑛𝑒𝑢𝑡𝑟𝑎𝑙 𝑎𝑚𝑖𝑛𝑜 𝑎𝑐𝑖𝑑 = p𝑘𝑎,1 + p𝑘𝑎,2⁄
2
 Pass through a secondary buffer phase as more base is added since the amino group
begins to deprotonate.