5. ONIUM COMPOUNDS
201
kenzie's (85) have found that the ability of the rat to accumulate
ergothioneine in its erythrocytes is dependent both on the sex and age
of the animal. In both sexes the ergothioneine level increases in the
first 90 days of life thereafter remaining constant in the female, while
doubling in the male. Moreover, this sex linked difference was not affected in the male by castration or by administration of estrogens, or
both. On the other hand in female rats treated with testosterone the
blood levels increased to approach the level found in the male. No explanation can be offered at the present time for this difference.
c. Biochemical and Physiological Role. The biochemical function of
ergothioneine is still obscure. The presence of a thiol group prima facie
suggests that this betaine may function as a reducing agent. As is well
known there is a variety of naturally occurring sulfhydryl compounds
and evidence is accumulating that they are not metabolically equivalent
since some are specifically involved in well defined biochemical reactions. As yet, however, no specific role can be assigned to the thiol
group of ergothioneine, but it may be recalled that as far back as 1911
Barger and Ewins (67) recognized the difference between the thiol
groups of ergothioneine and cysteine. In the first place the former is
relatively stable to alkali and is oxidized to sulfuric acid under conditions which result in the formation of a sulfonic acid from cysteine; it
also differs from other thiol compounds in that it does not give a nitroprusside reaction or the Grote (86) reaction typical of thioureas and
substituted thioureas (87). It will, however, form a disulfide under
suitable conditions (88) although at physiological pH the equilibrium
is completely towards the reduced state. As to its ability to form mixed
disulfides there are conflicting reports (88, 89) but at any rate the
formation of mixed disulfides is considerably more difficult than with
other thiols.
Ergothioneine is not a methyl donor and no reaction involving participation of its onium group has been discovered. Chemically, it will
readily undergo a typical elimination reaction in alkali, yielding thiolurocanic acid and trimethylamine; recently it has been shown that an
analogous enzymatic reaction takes place in bacteria (90).
The most suggestive clue to a biochemical role for this compound
has recently emerged from the work of Grossman and Kaplan (91) on
the base exchange reaction catalyzed by DPNase. These authors found
that ergothioneine is required to initiate a base exchange reaction with
Neurospora DPNase or erythrocyte RNase, which enzymes, in the absence of ergothioneine, will catalyze only the hydrolytic cleavage of
DPN or NR respectively at the nicotinamide ribose linkage. (See also
Section V,B,3). It may be particularly significant that, in Neurospora,
201
kenzie's (85) have found that the ability of the rat to accumulate
ergothioneine in its erythrocytes is dependent both on the sex and age
of the animal. In both sexes the ergothioneine level increases in the
first 90 days of life thereafter remaining constant in the female, while
doubling in the male. Moreover, this sex linked difference was not affected in the male by castration or by administration of estrogens, or
both. On the other hand in female rats treated with testosterone the
blood levels increased to approach the level found in the male. No explanation can be offered at the present time for this difference.
c. Biochemical and Physiological Role. The biochemical function of
ergothioneine is still obscure. The presence of a thiol group prima facie
suggests that this betaine may function as a reducing agent. As is well
known there is a variety of naturally occurring sulfhydryl compounds
and evidence is accumulating that they are not metabolically equivalent
since some are specifically involved in well defined biochemical reactions. As yet, however, no specific role can be assigned to the thiol
group of ergothioneine, but it may be recalled that as far back as 1911
Barger and Ewins (67) recognized the difference between the thiol
groups of ergothioneine and cysteine. In the first place the former is
relatively stable to alkali and is oxidized to sulfuric acid under conditions which result in the formation of a sulfonic acid from cysteine; it
also differs from other thiol compounds in that it does not give a nitroprusside reaction or the Grote (86) reaction typical of thioureas and
substituted thioureas (87). It will, however, form a disulfide under
suitable conditions (88) although at physiological pH the equilibrium
is completely towards the reduced state. As to its ability to form mixed
disulfides there are conflicting reports (88, 89) but at any rate the
formation of mixed disulfides is considerably more difficult than with
other thiols.
Ergothioneine is not a methyl donor and no reaction involving participation of its onium group has been discovered. Chemically, it will
readily undergo a typical elimination reaction in alkali, yielding thiolurocanic acid and trimethylamine; recently it has been shown that an
analogous enzymatic reaction takes place in bacteria (90).
The most suggestive clue to a biochemical role for this compound
has recently emerged from the work of Grossman and Kaplan (91) on
the base exchange reaction catalyzed by DPNase. These authors found
that ergothioneine is required to initiate a base exchange reaction with
Neurospora DPNase or erythrocyte RNase, which enzymes, in the absence of ergothioneine, will catalyze only the hydrolytic cleavage of
DPN or NR respectively at the nicotinamide ribose linkage. (See also
Section V,B,3). It may be particularly significant that, in Neurospora,