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History
of Glutathione |
 |
| Discovery and Isolation |
|
In
1888, de Rey-Pailhade found evidence that yeast cells contain a substance
that is responsible for forming hydrogen sulfide when these cells were
crushed with elemental sulfur. In a brilliant series of papers, J. de
Rey-Pailhade described his repetition of the work of J. B. Dumas. He reported
that it is also present in beef muscle, beef liver, sheep brain, lamb
small intestine, fish muscle, egg white, fresh sheep blood, and freshly
picked asparagus tips. He also noted that it was more stable in winter
than in summer, that it bleached several dyes, and was destroyed by reaction
with chlorine, iodine, and bromine. de Rey-Pailhade suggested the name
philothion (from the Greek “sulfur loving”) for this substance.
He believed that it had an important biological role because of its apparent
ubiquity in living cells. He proposed that philothion contained labile
hydrogen and, following an idea proposed by A. Heffter, concluded that
it contains cysteine. |
Elucidation of some of its properties |
Heffter
and V. Arnold (see below) showed that many animal tissues and extracts
of tissues gave a positive nitroprusside reaction (indicative of a strong
reducing agent). It was suggested that the compound responsible was cysteine.
Heffter felt that a thiol-containing compound was responsible for the
reducing properties of cells and cellular oxidative phenomena. |
Hopkins
found that the compound responsible for the positive nitroprusside reaction
in muscle, liver, and yeast could be extracted with water, and he isolated
what he initially believed to be a dipeptide containing glutamate and
cysteine. Hopkins renamed philothion as glutathione. |
 |
Determination of its structure as L- -glutamyl-L-cysteinylglycine |
de
Rey-Pailhade’s philothion reflected the ability of the compound
to react with sulfur, Hopkins’ work demonstrated that glutathione
contains sulfur. Hopkins, and independently Kendall et al., later demonstrated
that the peptide contains glycine. The structure of glutathione was deduced,
elucidated from chemical studies (Quastel et al., 1923; Stewart &
Tunnicliffe, 1925; Hunter & Eagles, 1929; and Pirie & Pinhey,
1929) and established by synthesis (Harlington & Mead, 1935; DuVigneaud
& Miller, 1936).
|
This
material can be found in Chapter 1, "On the Biochemistry of Glutathione",
by Alton Meister in Glutathione Centennial, Academic Press, Inc. (1989)
pp. 3-21. This book is out of print but many medical libraries carry it. |
| References |
| J.
de Rey-Pailhade, (1888) C. R. Acad. Sci. 106, 1683-1694. J. de Rey-Pailhade, (1888) Bull. Soc. Hist. Nat. Toulouse, pp. 173-180. J. de Rey-Pailhade, (1893) C.R. Sess./Assoc. F. Av. Sci. Pt. 1, p. 193. J. de Rey-Pailhade, (1907) Bull. Gen. Ther. CLIV, pp. 740-742. Heffter, A. (1908) Med. Naturwiss. Arch. 1, 81-103. Arnold, V. (1911) Z. Phys. Chem. 70, 300-325. Quastel et al. (1923) – [established the gamma-glutamyl linkage to cysteine] Stewart and Tunnicliffe (1925) – [synthesized -GLU-CyS] Hunter and Eagles (1927) – [tripeptide of GLU-CyS- SER] Pirie and Pinhey (1929) – [proved structure by titration] Hopkins, F.G. (1929) J. Biol. Chem. 84, 269-320. Kendall, E.C., MacKenzie, B.F., and Mason, H.L. (1929) Staff Meetings of the Mayo Clinic 4, 264-266. Kendall, E.C., Mason, H.L. and MacKenzie, B.F. (1930) J. Biol. Chem. 88, 409-423. Harlington, C.R. and Mead, T.H. (1935) Biochem. J. 29, 1602-1611. DuVigneaud, V. and Miller, G.L. (1936) J. Biol. Chem. 116, 469-476. Hopkins, F.G. (1921) Biochem. J. 15, 286-305. |
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