Proline, Valine and Methionine

From first to last it took over 100 years for the 20 common amino acids to be discovered and named (not always in that order). This century straddled the invention of the systematic naming conventions we know today, and the ability of chemists to elucidate the structures of molecules made drastic improvements. So, by the time the last few common amino acids were discovered, the allocation of a name no longer needed to be based on what they were made from, but what they were themselves. Unlike saturated fatty acids, where the systematic names are so short and simple that newer examples can use these as their sole labels, amino acids are just complicated enough to need shorter monikers. In fact, three of the group have names that are literal shortenings of the systematic name.

Proline

First synthesised in 1900, proline wasn’t discovered to be a component of proteins until a year later. Proline was originally referred to by the systematic name “pyrrolidine-α-carbonsäure” (pyrrolidine-α-carboxylic acid);1,2 then in 1904, while reporting the synthesis of dipeptides formed with this amino acid, Fisher stated:

“Since α-pyrrolidinecarboxylic acid is a component of most protein substances…the word α-pyrrolidinecarboxylic acid is too long to name such combinations. We therefore consider it expedient to suggest the abbreviated word ‘proline’, the derivation of which from pyrrolidine is easy to understand.”

Thus coining the common name by pulling a few letters out of its longer form.

The name pyrrolidine can be further traced back to the unsaturated form of this 5-membered N-heterocycle, pyrrole, with the -id- and -ine added by Ludwig Knorr as a method to distinguish the names of the saturated form.3 The name pyrrole, or ‘pyrrol’ in the original German, was named by Runge in 1834 in a spree of colour-related namings for oils isolated from coal-tar. In these names the -ol comes from the Latin oleum, meaning oil, and first part comes from the Greek for a particular colour.4 These included kyanol, now aniline, from kyanos (Greek for blue) and leukol, now quinoline, from leukos (Greek for white). Pyrrol was named from pyros, which is Greek for reddish/fiery, due to the purple/red colour a hydrochloric acid-moistened splint would go when held in its vapour. Interestingly, this paper from Runge is also the first report of the isolation of phenol, which he called karbolsäure and was anglicised to carbolic acid (it still surprises me that the ‘carbolic acid’ pioneered as antiseptic by Joseph Lister was what we know now as phenol…no wonder people didn’t like getting it on their skin).

Valine

Valine sets the record for the longest time between initial discovery, and the coining of the name we use for it today, at 50 years. Valine was first isolated in 1856 by the Austrian-German chemist Eugen Freiherr von Gorup-Besanez from a sample of pancreas. He established that it was a new substance and identified the chemical formula, but went no further.5

A couple of decades later, in 1879, the French chemist Paul Schützenberger identified valine as a component of albumin, suggesting the two possible names of “l’acide amidovalérique” or “butalanine”.6 It’s probably a good job butalanine didn’t stick: the structural relationship with alanine doesn’t work in the same way as phenylalanine, so that could have caused its own confusion.

It wasn’t until 1906, when Emil Fischer identified which optical isomer was present in proteins, that the name “valin” (anglicised to valine) was suggested, as a shortening of “d-α-aminoisovaleriansaure” (d-α-aminoisovaleric acid).7 As can be read in my post on saturated fatty acids, valeric acid got its name as it was first isolated from the valerian plant.

Methionine

The compounds that would be named methionine was first identified in 1922 by J. Howard Mueller as “a new sulphur-containing amino acid isolated from casein”.8 Previously, cystine was the only known amino acid to provide the sulphur content of proteins. A few structures were suggested in the proceeding years, with one option being ethyl cystine, until experiments in 1928 by Barger and Coyne identified the methylthiol group and the correct structure was pinpointed.9 The pair took the opportunity to provide this compound with a shortened name:  

“Since the amino-acid has a good title to be regarded as a constituent of protein, a shorter name than y-methylthiol-a-aminobutyric acid seems desirable, and, after consultation with Dr Mueller, we suggest for it the name methionine, in allusion to the characteristic grouping.”9

The characteristic grouping mentioned would be the methylthiol group, shortened to methio-.

To trace this name further back, you may wish to refer to my previous article for the etymology of methyl. Thio- is taken from the Greek word theion, meaning sulphur, and this prefix is used for compounds with sulphur in them.3 Very much a “say what you see” situation.

References

1.          Willstätter R. Synthese der Hygrinsäure. Berichte der Dtsch Chem Gesellschaft. 1900;33(1):1160-1166. doi:10.1002/cber.190003301201.

2.          Vickery HB, Schmidt CLA. The History of the Discovery of the Amino Acids. Chem Rev. 1931;9(2):169-318. doi:10.1021/cr60033a001.

3.          Flood WE. The Origin of Chemical Names. Osbourne Book Co. Ltd.; 1963.

4.          Runge F. “Ueber einige Produkte der Steinkohlendestillation” [On some products of coal distillation]. Ann der Phys und Chemie. 1834;31:65-78.

5.          von Gorup-Besanez E. Ueber die chemischen Bestandtheile einiger Drüsensäfte. Ann der Chemie und Pharm. 1856;98(1):1-43. doi:10.1002/jlac.18560980102.

6.          Schützenberger P. Mémoire sur les matiéres albuminoides. Ann der Phys und Chemie. 1879;16(5):289-419. https://gallica.bnf.fr/ark:/12148/bpt6k34856c/f286.imageURL:https://gallica.bnf.fr/ark:/12148/bpt6k34856c/f286.image

7.          Fischer E. Spaltung der α-Aminoisovaleriansáure in die optisch activen Componenten. Berichte der Dtsch Chem Gesellschaft. 1906;39:2320-2328.

8.          Mueller JH. A new sulphur-containing amino acid isolated from casein. Proc Soc Exp Biol Med. 1922;19(4):161-163.

9.          Barger BYG, Coyne FP. The Amino-Acid Methionine; Constitution and Synthesis. Biochem J. 1928;22:1417-1425.

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