What Is the Redox Potential of Ergothioneine?

The citation given for the redox potential of ergothioneine (−0.06 V) cited by Steyn and coworkers (Cumming et al., 2018), and many review articles is the monograph by Jocelyn (1972) (see Table 18 on page 56). However, this is not the original reference. The footnote for the value given for ergothioneine is a reference by Calvin from Glutathione: Proceedings of the Symposium held at Ridgefield, Connecticut. The year given by Jocelyn is 1956, when in fact the proceedings were published in 1954 (Calvin, 1954). On page 20 in Table 4 of the chapter by Calvin, the redox potential is given as −0.06 V.

This measurement was not made by Calvin! The footnote in this chapter for the value for ergothioneine is a reference by Ryklan and Schmidt, which was published in the University of California Publications in Physiology (Ryklan and Schmidt, 1944). I must point out that the value of −0.06 V must be viewed with suspicion. In the article by Ryklan and Schmidt, the value for the redox potential for glutathione (GSH), measured by the same method as that of ergothioneine, is given as +0.03 V. The redox potential of GSH has been measured multiple times and the widely accepted value is −0.24 V.

In a contemporaneous review of the Proceedings on Glutathione mentioned earlier published in Science Progress, C. Long specifically notes the anomalously positive redox potential of GSH (determined by Ryklan and Schmidt) compared with similar thiols as well as the unusual structure proposed for GSH by Calvin based on this value (Long, 1955). Calvin posited that the structure of GSH was that of a thiazolidine ring. We know that this is incorrect. The reason for this invalid measurement for GSH is surely related to the iodine electrode system used by Ryklan and Schmidt.

Two lessons should be drawn here. First, although it is possible that the redox potential for ergothioneine measured by Ryklan and Schmidt is correct, it should be viewed with some degree of skepticism and another measurement should be made with an alternative method to verify this value. Second, original source material should always be cited instead of citing the value through a review article, which itself may have been obtained from another nonoriginal source. It is interesting to note that the article by Ryklan and Schmidt has been cited 42 times according to Google Scholar. By my count, only one of these citations is related to ergothioneine; Donald Melville's excellent review in the book series Vitamins & Hormones in 1959 (Melville, 1959). What I believe has happened since then is that the reference to the original measurement has gotten lost in the mist of time as others have either cited Melville's or Jocelyn's reviews. As such, nobody has questioned the validity of the original measurement.