L -Proline

December 04, 2017
I’m an amino acid that may have been a key to evolution.
What molecule am I?

The amino acid L-proline is considered to be nonessential because humans and other animals can biosynthesize it, mainly from another nonessential amino acid, L-glutamic acid. Proline is unusual in that it is heterocyclic, and thus is the only natural amino acid that contains a secondary amine group. Only the L-enantiomer is found in nature.

Proline also is unusual because it was synthesized before it was isolated from natural sources. In 1900, chemistry Nobel Prize–winning German chemist Richard M. Willstätter prepared the D,L-racemate from N-methylproline. The following year, Emil Fischer, another German Nobel laureate, isolated the L-form from egg albumen and hydrolyzed casein.

Proline, like all natural amino acids, is used for biosynthesizing proteins. The rigid five-membered ring in proline gives proteins made from it significantly different secondary structures from proteins made from open-chain proteins.

In 2002, Mohammed Movassaghi and Eric N. Jacobsen at Harvard University introduced the notion that proline is the “simplest enzyme”. At that time, several researchers were using proline as an asymmetric catalyst as though it was a new thing; earlier work using proline had been overshadowed by the advent of metal-based asymmetric catalysts. Movassaghi and Jacobsen declared that it was high time for chemists to realize that asymmetry could be achieved with simple compounds and without the use of metals.

A few years later, Eric Smith of the Santa Fe Institute and coauthors elaborated on the simplest enzyme concept. They argued that “small molecule catalysis is a finding of utmost importance for the origin of biochemistry”. In other words, small molecules, and not large, complex enzymes, were the only catalysts available to promote prebiotic evolution.

L-Proline fast facts

CAS Reg. No. 147-85-3
Molar mass 115.13 g/mol 
Formula C5H9NO2
Appearance White crystals 
Melting point 205–228 ºC (dec.)*
Water solubility 162 g/L
Chemical Abstract Service - a division of ACS

Learn more about this molecule from CAS, the most authoritative and comprehensive source for chemical information.

Molecule of the Week needs your suggestions!

If your favorite molecule is not in our archive, please send an email to motw@acs.org. The molecule can be notable for its current or historical importance or for any quirky reason. Thank you!

Stay Ahead of the Chemistry Curve

Learn how ACS can help you stay ahead in the world of chemistry.