Non-Polar Hydrophobic Amino Acids

Hydrophobic, as the name implies is hydro water, phobic fearing. Hydrophobic amino
acids have little or no polarity in their side chains. The lack of polarity means they have no
way to interact with highly polar water molecules, making them water fearing.
There are only five atoms that will appear in your amino acid variable groups: H, C, N, O,
and S.
Only consider polarity when you have N, O, S as the majority factor. Ill point these out as
they occur. However, if all you see are Cs and Hs you should automatically recognize a
water-fearing amino acid.

Glycine
Gly
G
Glycine is a unique amino acid in that it doesnt really have an R group. When you think
variable R group, you should think of carbon attached to other atoms. But glycine only has
a hydrogen at its side chain position. Since glycine has 2 hydrogen atoms, one each on the
parent and side chain, its the only symmetrical and thus achiral amino acid. Since hydrogen
is non-polar, glycine is a hydrophobic amino acid. The Hydrogen side-chain makes glycine
the smallest amino acid.

Alanine
Ala
A
Alanine is a simple amino acid which has just a methyl or CH3 group as its side chain. Since
you see nothing but carbon and hydrogen, Alanine is a non-polar hydrophobic amino acid.
Its important to recognize that this is a very small amino acid and capable of being wedged
into tight loops or chains.

Valine
Val
V
Valine is another simple amino acid with just an isopropyl variable group. Just like alanine,
we see nothing but carbon and hydrogen, making valine a non-polar hydrophobic amino
acid.

Leucine
Leu
L
You can recognize leucine as having the same variable group as valine but with an extra CH2
group. Or you can simply recognize its isobutyl side chain.
See this video if youre not familiar with branched side chains like isopropyl or sec-butyl.
Since leucine has just Cs and Hs, its a water fearing non-polar amino acid.

Isoleucine
Ile
I
Isoleucine, as the name implies, is an isomer of leucine. The difference is the placement of
the CH3 for a sec-butyl rather than a isobutyl side chain. Just like its isomer, isoleucine is
nonpolar and hydrophobic.

Methionine
Met
M
Methionine is the first potentially tricky amino acid. Its side chain contains mostly Cs and Hs
but with an embedded sulfur atom. While you may think its hydrophilic, pay careful
attention to the location of the sulfur atom. Embedded in the chain and attached to just
carbon atoms, sulfur is partially hidden from the outside environment.
While you dont have to know electronegativity values for the MCAT it helps to understand
that S = 2.58 and C = 2.55. Since the difference in electronegativity is less than 0.5, there is
NO polarity on this sidechain.
You must also recognize methionine as the start codon AUG in RNA translation to proteins.

Phenylalanine
Phe
F
To help you remember that Phenylalanine is F remember that ph is pronounced as an F.
Dont mix this up with P for proline.
Pay attention to the structure of phenylalanine. It has a single carbon group with an attached
benzene ring. Phenyl is the name for a benzene substituent, and this molecule has a
benzene (phenyl) attached to the structure of alanine. Since phenylalanine has nothing but
Cs and Hs in its aromatic side chain, it is nonpolar and hydrophobic.

Tryptophan

Trp
W

This is a tricky one. Notice the N-H in this side chain. N-H should be polar and capable of
hydrogen bonding. However, there are two reasons this amino acid is still non-polar and
hydrophobic.
1.

The N-H group is a tiny portion of the very large side chain.

2.

Look carefully at nitrogen, and more importantly, at its lone pairs. Nitrogens electrons
are integral to the conjugated aromaticity for the tryptophan side chain. In other words,
think of its electrons as too distracted by resonance to pay much attention to the
external water environment.

The MCAT requires you to recognize that this is a large and bulky amino acid. But since its a
multiple choice exam you can simply memorize that tryptophan is the ONLY amino acid with
TWO fused rings.
In fact, its so big it can TRIP (trp) over itself and cry out Waaaaaa (W)
(Note on mnemonics: The funnier, weirder, or dirtier the mnemonic, the more likely you will
remember it. Keep this in mind for med-school.)

Pro
P

Proline

Proline is a unique amino acid since its THE ONLY ONE that incorporates the backbone into
its side chain. The proline side chain is a 3-carbon chain that loops around and attaches back
to the parent amino group. This means that unlike the other amino acids, proline does NOT
have a hydrogen atom on its nitrogen when part of a polypeptide chain.
However, you cannot forget that nitrogen is NOT REALLY part of the variable group, which
means it cannot contribute any polarity. Since we just have 3 CH2 groups to analyze we get
a nonpolar hydrophobic side chain. This parent-loop creates a bulge and does not allow a
proline-containing chain to be linear, which means youll often find it in loops and at the end
of an alpha helix.

Polar Hydrophobic Amino Acids

*This is a sticky section, and depending on where you research you may find the following
categorized as polar or nonpolar, hydrophilic or hydrophobic. Pay attention to the presence
of polar groups that are small compared to the overall sidechain, or very weakly polar and
therefore hydrophobic.

Cys
C

Cysteine

Cysteine has a slightly polar S-H, but its polarity is so mild that cysteine is unable to properly
interact with water making it hydrophobic.
Cysteine is a very important amino acid when it comes to tertiary and quaternary structure.
Most side-chain interactions include polar/charged interactions or non-polar Van Der Waals
and London dispersion. However, cysteines side chain is capable of forming a disulfide
bridge, which is a covalent bonds between 2 sulfur atoms through side chain oxidation and
removal of 2 hydrogen atoms. This covalent bond is much stronger and more permanent
when compared to the standard tertiary and quaternary interactions.
This is also the cause for experimental error in determining protein size/length for proteins
with multiple subunits.

Tyr
Y

Tyrosine

Some students see this as OH leaking from a tire (tyr).

Take a close look at tyrosine. What do you see? It looks like the aromatic phenylalanine with
an OH group at the para position (ortho/meta/para 2nd video).
On the one hand, we have a very polar and hydrogen-bond capable OH group, but on the
other hand, the OH is tiny when compared to the size of the benzyl group (CH2-phenyl). This
conundrum is a common source of confusion, but if you understand this, youll recognize that
tyrosine, while polar, is still a hydrophobic amino acid.

Polar Hydrophilic Amino Acids

Hydrophilic as the name implies comes from hydro-water and philic loving.
Polarity comes from a 0.5-1.9 difference in electronegativity between bound atoms. While
you dont have to know these values for the MCAT, you should recognize that polar bonds
will exist when N and O are bound to non-carbon atoms.
The electronegativity difference is enough to create a slight separation of charge or polarity.
And since like attracts like, these partially charged groups will be attracted to oppositely
charged or partially charged groups such as water. These groups will twist the polypeptide
chain in order to interact with each other and with water.
Hydrophobic groups will twist away from these side chains.

Ser
S

Serine

Think of serine as alanine with an OH group attached. Unlike tyrosine, the OH is the majority
in this molecule and its polarity is enough to influence the entire group. This makes series
polar and very hydrophilic.

Thr
T

Threonine

There are multiple ways to look at this group. You can think of it as serine with an extra
methyl group, or as valine but with an OH replacing one of the methyl groups. I remember
THREEonine as having 3 different groups: CH, CH3, and OH.
Like serine, this variable group is polar and hydrophilic.

Asparagine
Asn
N
Try this: Slur your speech as you say asparagine really fast. It sounds like youre saying
ASN, which is how I remember the 3-letter abbreviation for this amino acid. The NH2 at the
end of this molecule makes you think base, but look at its neighbor. NH2 near a carbonyl
forms an amide, which doesnt like to act as an acid or base under standard physiological
conditions. However, with partial charges and H-bonding capability at both the carbonyl
oxygen AND the NH2 groups, we get a polar hydrophilic amino acid.

Gln
Q

Glutamine

I think of both glut amino acids as gluttons having consumed an extra CH2 group.
Glutamine has the same structure as asparagine but with an extra gluttonous CH2 in its
chain. Just like asparagine, it is polar and hydrophilic.

Acidic and Basic Amino Acid Side Chains

Acidity and basicity in amino acids is yet another source of confusion among students. If it
starts out as an acid, does it become a base? How do I find the charge? And so on.
Heres the trick: a carboxylic ACID in the side chain will give you an acidic amino acid. When
a carboxyl group is deprotonated, you get a conjugate base SALT. So if you see the salt
version of a carboxylic acid side chain, while it is TECHNICALLY a conjugate base, well
simply refer to it as the salt version of the acidic amino acid. Same for the base. Look out for
non-distracted nitrogen atoms in the side chain.

Acidic Amino Acids

The acidic amino acids should look very familiar compared to asparagine and glutamine. And
thats because everything about them is the same except for the terminal functional group.
Amides (discussed above) are polar, but if the NH2 is swapped for an OH group, you get an
acidic carboxyl group.

Aspartic Acid / Aspartate

Asp
D

Aspartic acid refers to the protonated acidic form of the amino acid. When deprotonated,
youll often see the conjugate base salt referred to as aspartate. This is the standard
nomenclature for carboxylic acids.

Think of ethanoic acid. Its common name is acetic acid. When deprotonated you get acetate.
Acids are very stable in water since they are partially charged in their protonated form and
fully charged in their deprotonated form. This makes them highly hydrophilic.

Glutamic Acid / Glutamate

Glu
E

Once again we have a glutton amino acid with an extra CH2 group. Glutamic Acid refers to
the protonated acidic form, and glutamate refers to the deprotonated conjugate base/salt
form.
Like aspartic acid, glutamic acid is very stable in water and thus hydrophilic.

Basic Amino Acids

Basic amino acids contain a nitrogen atom with a lone electron pair capable of attacking a
hydrogen atom. When a basic amino acid is subjected to a low (acidic) pH, it will grab one of
the free protons in solution to form a conjugate acid salt. These are easily recognize by the
positive nitrogen in the side chain. Unlike the acidic amino acids, there are no commonly
used names to memorize for these conjugate salts.

Lysine
Lys
K

Lysine is a simple basic amino acid. Despite a long and potentially hydrophobic chain, it has
a basic NH2 at the end. In its basic deprotonated form, lysine is neutral and hydrophilic;

however, if found in physiological pH, lysine will pick up an H+ from solution to form an
NH3+ salt. Salts are charged and therefore definitely hydrophilic

Arginine
Arg
R

Arginine is confusing and makes me say ARGh or R for short. Why? The basic portion of this
variable group consists of an NH, C=N-H and NH2.
The 2 single-bound nitrogen atoms can use their lone pairs to resonate with the carbon and
double bound nitrogen atom. This makes their electrons UNAVAILABLE for acting as a base.
However, the double-bound nitrogen uses its pi bond to resonate, leaving its free lone pair
(shown in black) to act as the basic nitrogen on this group.
Argh!

Histidine
His
H

Histidine is another tricky base for the same reason as arginine. WHICH nitrogen is the basic

one? Look at the drawing here, particularly at the lone pairs on the 2 nitrogen atoms. The
histidine ring is a heterocyclic aromatic compound. The upper nitrogen atom does not have a
pi bond. This means it must use its lone pairs to participate in resonance.
The lower nitrogen atom already has a resonating pi bond. This leaves its lone electrons
(shown in black) free to grab a proton, making this the basic atom.
In conclusion
Amino acids are a critical component to biological structures and to your understand of
biology and biochemistry on the MCAT. And so, as you attempt to memorize everything
about these 20 amino acids, its important that you also understand why you have polar and
nonpolar amino acids, what makes the variable group hydrophobic or hydrophilic, and of
course, the logic behind protonated/deprotonated acidic and basic amino acids.