Leucine, Isoleucine and Arginine

Anyone who has done even a small amount of organic chemistry in the lab will know that “white solid” is an incredibly common description of an organic compound. Given their ubiquity, one may think it a little short-sighted to name such compounds after this less-than-unique property. Nevertheless, that does indeed seem to be the origin of the names leucine and arginine.

Leucine

Leucine is very likely the first amino acid to receive the name we use today. I say likely because we have evidence that leucine was named in 1820,1 but the naming of asparagine seems to have occurred at some point between its discovery in 1806 and it being used in 1826 in a manner which suggests it was an established term.2,3

The name leucine was assigned, initially provisionally, by the French chemist Henri Braconnot in 1820, after he isolated a sample from acid hydrolysis of muscle fibre.1 He named the crystalline precipitate from the Greek word leukos, meaning white, due to its colour.

Interestingly, leucine was only one of a number of possible names we could have retained. A year beforehand, another French chemist, Proust, isolated the first known sample of leucine during fermentation experiments to determine the substances to which different cheeses owe their flavours. He named one of the compounds isolated “oxide caséeux”, from the Latin caseus, meaning cheese. Braconnot was seemingly unaware of the association between leucine and oxide caséeux at the time. However, in 1827 he published a paper reproducing Proust’s fermentation experiments. Upon isolating and performing limited analyses of oxide caséeux, he decided that it did not contain very much oxygen so was inappropriately named. Instead he suggested that, as it seems to form whenever animal substances are allowed to putrefy, it should be called “aposépédine” from the Greek aposapedon, meaning product of decay. It took until 1839 for someone to establish that these two compounds were one and the same, and the earlier name stuck. In Braconnot’s defence, he was working at a time with pretty crude purification and analytical techniques so it would have been very hard to tell that they were the same compound (I will also allow the lack of good purification techniques to be a reasonable defence for why the compound being white may not have been that common at the time).4 However, while having named one of the fundamental building blocks of life is impressive…to have named it twice just seems greedy.

Isoleucine

Perhaps the simplest explanation of the lot, this one hardly deserves its own section: it’s an isomer of leucine!

In 1901, Emil Fischer was investigating the separation of amino acids by distillation, and was attempting to purify the leucine fraction.4 He found that subsequent crops of crystals had different optical rotations and varied solubilities, but wasn’t able to fully separate identify the cause. The explanation of this oddity came from Felix Erlich in 1903 who established that a natural isomer of leucine was present: isoleucine.5

Arginine

Arginine is one of the annoying number of examples where the person who named it didn’t explain their reasons very well at all.

In 1886 the German chemists Schulze and Steiger reported the isolation of a new base from lupine seedlings.6 By adding phosphotungstic acid to extracts from these seedling, a precipitate formed that is described as “sehr starken weissen” (very strong white). This precipitate was purified, the nitric acid salt formed, and the base was given the name “Arginin”. And that is the full extent of the explanation we are given!

There are two competing theories for the root word for arginine. One possibility is the Latin word argentum, meaning silver, as it “forms characteristic compounds with certain metal salts, e.g. with silver salts” (an explanation taken from an etymological dictionary).7 Similarly, the Greek word argiros, also meaning silver, has been suggested, apparently due to the silver-white appearance of arginine nitrate.8 However, neither of these variations on a theme really stand up to a reading of the original publication.

The other option, provided as the explanation by the Oxford English Dictionary, is the Greek word arginoeis, meaning “bright-shining, white”.9 This has also been attributed online to the appearance of arginine nitrate, but the original text doesn’t make much of a song and dance about the appearance of this particular salt. However, as previously note, it does, very prominently in the first paragraph, emphasise the ‘very strong white’ colour of the precipitate with phosphotungstic acid. A history of the discovery of amino acids published in 1931 mentions that “Schulze had long known that phosphotungstic acid gave white precipitates when added to plant extracts and also that these precipitates contained nitrogen”,4 which suggests to me that it is likely to be this impure intermediate that was the focus, and became the inspiration for the name.

References

1.          Braconnot H. Sur la conversion des matieres animales en nouvelles substances par le moyen de l’acide sulfurique. Ann Chim Phys. 1820;13:113-125.

2.          Vauquelin, Robiquet. Découverte d’un nouveau principe végétal dans les Asperges (asparagus sativus. LINN.). Ann Chim. 1806;57:88-93.

3.          Dulong. Analyse chimique de la racine d’asperge. J Pharm. 1826;12:278-284.

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

5.          Ehrlich F. Ueber Isoleucin. Chemiker-Zeitung. 1903;67(14).

6.          Schulze E, Steiger E. Ueber einen neuen stickstoffhaltigen Bestandtheil der Keimlinge von Lupinus luteus. Berichte der Dtsch Chem Gesellschaft. 1886;19:1177-1180. doi:10.1002/cber.188601901266. URL:https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cber.188601901266

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

8.          Bioetymology: Arginine. Available at https://bioetymology.blogspot.com/2012/03/arginin-arg-r.html. [Accessed 25 October 2020].

9.          Oxford English Dictionary Entry: Arginine. Available at https://www.lexico.com/definition/arginin. [Accessed 25 October 2020].

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