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Biochemical
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Biochemical Education 26 (1998) 116-l 18
Amino acid names and parlor games: from trivial names to a
one-letter code, amino acid names have strained students’
memories. Is a more rational nomenclature possible?
M. Saffran
2331 Hempstead Road, Toledo, OH 43606, USA
Abstract
This paper explores the origins of the names and single-letter abbreviations of the 20 amino acids found in proteins. Knowing
the background of the nomenclature may help the student to remember the amino acid names and abbreviations. 0 1998 IUBMB.
Published by Elsevier Science Ltd. All rights reserved
1. Introduction
The English alphabet of 26 letters contains several
letters with almost identical sound values, e.g. c and s, c
and k and q. If these duplications are removed, the
alphabet consists of 23 different letters and sounds. The
Hebrew alphabet contains 23 letters; if the sound duplications
are removed, the alphabet contains 21 letters.
The Greek alphabet has 24 letters and 23 sounds. Most
other alphabets cluster around the 20 to 30 letter size. Is
the clustering a coincidence, or is it driven by a basic
biologic force? The proteins that make up much of our
body are constructed from simpler substances, the amino
acids. There are 20 different amino acids in proteins. (I
wonder if there is any relationship between the letters in
so many alphabets and the number of amino acids.)
All amino acids contain two identical chemical groups,
the amino group (-NH,) and an acid group (-COOH). In
addition, each amino acid has a characteristic side chain
or R group which provides the individuality of each
amino acid and determines its chemical properties. The
arrangement of different amino acids in a protein
molecule gives the protein its characteristics: its ability to
provide shape to a cell or body structure, its ability to
carry out its task of providing energy or of fighting off
infections, and so on. The 20 amino acids seem to have
the attributes of letters of an alphabet, which form the
protein words, which carry the message.
2. The names of the amino acids
During the nineteenth century, chemists, mostly in
Germany, purified and analyzed the then new family of
amino acids. Proteins were too complex to be studied by
the techniques of the nineteenth century, but heating the
proteins in acid or alkali separated the amino acids from
each other. The amino acids could now be isolated and
studied by available methods. By the beginning of the
twentieth century, 18 amino acids were identified as
components of proteins. As each amino acid was
described, the discoverer gave it a name depending upon
its source, its properties, or its chemical structure. Except
for the suffix -ine, for (am)-ine, in the name of most
amino acids, there was no systematic naming of the
amino acids. As a result students are faced with the task
of memorizing the names of the amino acids as an
exercise in rote learning. Also, the chemists of the
nineteenth century did not know that boiling in acid
destroyed two amino acids: these were not identified
until the first and third decades of the twentieth
century.
A good dictionary provides information about the
naming of the amino acids. My source is The American
Heritage Dictionary of the English Language, edited by
William Morris, published in 1970 by the American
Heritage Publishing Co. and Houghton Mifflin Co.,
Boston, MA. Glycine, the smallest amino acid, was so
0307-4412/98/$19.00 + 0.00 0 1998 IUBMB. Published by Elsevier Science Ltd. All rights reserved
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M. SafianlBiochemical Education 26 (1998) 116-118 111
named because it was sweet tasting. The prefixes, gly- or
glu-, are derived from the Greek y~orcspoa, meaning
sweet. The amino acid, arginine, was isolated as crystals
resembling white, shiny silver (apyrvo~ro in Greek).
Aspartic acid and asparagine were isolated from asparagus,
while glutamic acid and glutamine were named
after their source, the wheat protein, gluten. Histidine
was isolated from tissues (cf. histology, the study of
tissues), and lysine from tissues undergoing lysis, or
liquefaction. Alanine was so-called because of the
mistaken impression that it contained an aldehyde group
(Al-a-nine). Tyrosine was first isolated from cheese
(tupoa = Greek for cheese). Serine was isolated from
ser(ic)ine, a protein that adheres to silk @ericus is the
Latin adjective, silky). Cysteine was isolated from urine,
which comes from the urinary bladder, or cyst.
A few of the amino acids were named for their resemblance
to other chemicals or to their chemical components.
Methionine is a compound name composed of
Me(methyl)+Thio(sulfur)+N+ine. Phenylalanine is
indeed a phenyl group (benzene ring)+alanine. Proline
is named after the P(yr)ROL(ring) +ine. Threonine,
discovered in the 1930s was named after its resemblance
to the sugar, threose. Valine was named after VAL(eric
acid) + ine.
Tryptophan(e) was discovered in the early years of the
twentieth century and was named after the enzymes that
were used instead of hot hydrochloric acid to break down
the parent proteins: TRYP(sin) and pep(T)ic enzymes+OPHANE,
a made-up suffix, as in cellophane. Its
discovery was celebrated in verse in Bti&ter Biochemistry,
an informal publication of the Biochemistry
Department at Cambridge University, where tryptophane
was discovered:
In our laboratory, there are two classes.
Some are genii, others asses.
The former discovered tryptophane,
the latter flushed it down the drain.
3. Rational nomenclature
If the amino acids had been discovered in the
twentieth, rather than the twenty-first century, a more
rational nomenclature might have evolved. For example,
alanine, with its chain of three carbon atoms, might have
been named as a derivative of propane, the hydrocarbon
with a three-carbon chain: alanine = 2-amino propanoic
acid. In fact, the synonym for alanine in the Merck Index
of chemical compounds isjust that! Similarly, leucine can
be named as a derivative of the five-carbon chain,
pentane, as 2-amino, 4-methyl-pentanoic acid.
Another system of nomenclature can consider all
amino acids, except glycine, as derivatives of alanine. I
have already mentioned phenylalanine as an example.
Serine would then be 3_hydroxyalanine, and leucine,
3_dimethylmethylalanine, etc. But usage has enshrined
the original amino acid names in the literature and the
text books and change would be too disruptive.
4. Abbreviations
As methods evolved to study the amino acid composition
and sequence in proteins, writing out the full names
of the amino acids became tedious. A joint nomenclature
commission of the International Union of Pure and
Applied Chemistry (IUPAC) and the International
Unionof Biochemistry (IUB), chaired by H.B.F. Dixon
from the Department of Biochemistry in Cambridge,
examined the names of the amino acids and their derivatives,
along with the abbreviation of the amino acid
names to the first three letters of their names. The shortened
names became very popular. Soon, however,
complications arose. To avoid overloading the proofreading
skills of the scientific world, Asn replaced the
earlier Asp-NH, for asparagine and Glu.NH, became
Gln for glutamine. The easily confused pair, Tyr for
tyrosine and Try, for tryptophan, became Tyr
(unchanged) and Trp. Ileu for isoleucine was simplified
to Ile. Soon, the three-letter abbreviations became
tiresome to write, and a one-letter abbreviation system
was proposed by a group of Czech biochemists. A
20-letter amino acid alphabet was designed and adopted
by the IUPAC-IUB Joint Commission on Biochemical
Nomenclature. The deliberations and decisions of the
Joint Commission were published in about 10 of the
major biochemical journals in five languages (see Ref. [l]
for details).
5. The one-letter system
The simple approach, using the first letter of the name
of the amino acid, only sufficed for those compounds
with unique first letters: C could only stand for cysteine,
H for histidine, M for methionine, and V for valine. But
alanine, arginine, aspartic acid, and asparagine could not
all be represented by the first letter A! Glutamic acid,
glutamine, and glycine shared G. Leucine and lysine
begin with L. Threonine, tyrosine and tryptophan all
begin with T. The simplest of the amino acids with shared
initial letters was assigned that letter. Alanine became A,
glycine became G, leucine became L, and threonine
became T. For the others, the members of the Nomenclature
Committee of the Biochemical Society
apparently applied their skills at the parlor game of
charades, in which the participants guess the name of the
118 M. SafianiBiochemical Education 26 (1998) 116- I18
person or the object with the aid of visual clues. For
example, touching the nose and cupping the ear is the
clue for ‘sounds like nose’ or knows. And so arginine was
abbreviated to R, because arginine sounds like
‘R’-ginine. Aspartic acid was abbreviated to D, because
the amino acid’s name sounds like aspar-D-ic acid.
Similarly, glutamine became Q, sounds like Qlutamine,
and phenylalanine was abbreviated to F, for
F-enylalanine. Asparagine was abbreviated to N for
asparagi-N-e.
So why is glutamic acid represented by E? Because
aspartic acid is D, and glutamic acid is larger than
aspartic acid by one carbon atom, hence glutamic acid is
the next letter of the alphabet, E. While Leucine is L, the
other L is lysine. Because L is taken, for leucine, lysine
became K, next to L. Tyrosine is represented by Y for
t-Y-rosine. Finally, tryptophan is abbreviated to W
because the shape of the letter W reminded the
committee of the shape of the ring structure of atoms in
the side chain of tryptophan.
Most students are unaware of the ingenuity that
entered into these abbreviations, and they continue to
commit the list to memory. Dexter Moore [2] has
proposed an elaborate system of informative acronyms
to couple amino acid names, as represented by the first
letters, with their chemical characteristics and their
metabolic fates. Later, B.H. Nicholson [3] suggested a
modification of Moore’s scheme in which the amino
acids were represented by their official one-letter abbreviations.
I tried to use these mnemonics in lectures on the
amino acids to medical students and found that the
acronyms helped only as far as the next examination. In
view of the push to replace rote memory with understanding,
a better way might be to demonstrate very early
in a course the importance of biochemistry, and indeed
in all the life sciences, of knowing the structures of the
amino acids and their characteristics as intimately as
knowing one’s family and friends. Therefore, I began the
amino acid lectures by asking the students to write a list
of the names and characteristics (e.g. gender, age, height,
weight, personality, generosity, etc.) of 20 relatives and
friends. This exercise demonstrated that committing
such a list of details to memory is not an insurmountable
task and that matching the 20 amino acids and their
characteristics can be done easily and quickly.
6. Nomenclature problems continue
The apparent coincidence of 20 amino acids and 20+
letters in major alphabets has come full circle with the
assignment of 20 letters to the amino acids. Naming
newly discovered molecules is still a hit or miss activity.
Some new growth factors were named after their first
source, e.g. PDGF for platelet-derived growth factor,
from the platelets of the blood. Others are named for
their chemical and biological resemblance to well-established
hormones, e.g. insulin-like growth factors I and II.
Still others are named after their biological activity, e.g.
maganin (Hebrew for shield) for a protective protein,
and erythropoietin, for its ability to enhance the production
of erythrocytes or red blood cells. Confusion reigns
when several groups of investigators almost simultaneously
isolate the same agent from several sources. Each
laboratory then gives the agent a name based upon the
source or biological activity or even after the university in
which the laboratory is located (e.g. tuftsin, after Tufts
University in Boston). Eventually the realization that
several groups have discovered the same substance
results in a shakedown of the names into the one that is
most publicized, or most convenient or easiest to
remember. The other terms wither and disappear.
Perhaps it is time to apply the ingenuity used in
devising the single letter code for amino acids to a more
rational approach to naming newly discovered
molecules.
Acknowledgements
I am indebted to H.B.F. Dixon for clarification of the
details of the deliberations and recommendations of the
JCBN.
References
[l] IUPAC-IUB Joint Commission on Biochemical Nomenclature
(JCBN), Nomenclature and symbolism for amino acids and
peptides, recommendations 1983, Biochem. J. 219 (1994)
345-373.
[2] D.S. Moore, Biochemically informative acronyms for the twenty
common amino acids, Biochem. Educ. 15 (1987) 74-76.
[3] B.H. Nicholson, Amino acid acronyms (letter to the editor),
Biochem. Educ. 16 (1988) 49.