5. ONIUM COMPOUNDS
229
Thus, as noted in an earlier section, transalkylation reactions may be
viewed as nucleophilic substitutions in which there is attack upon one
of the carbons immediately adjacent to the positively charged sulfur.
The over-all result is displacement of a thioether from this carbon atom
synchronous with formation of a new bond between the same carbon
atom and the attacking reagent, the "acceptor." In the present case, the
nucleophilic attack may be spearheaded by a nitrogen, oxygen, or even
carbon atom of the acceptor molecule, and it may be forecast, from
what is known about transmethylation from other sulfonium compounds,
that compounds containing a sulfur atom will be likewise found capable
of attacking adenosylmethionine. In each case an enzyme specific for
the acceptor compound has been found and significant comparative data
are listed in Table VIII. It is interesting to note that the specific activities of the partially purified enzymes correlate pretty well with the
rates that could be expected on the basis of the physiological significance of the different reactions.
In addition to the alkylpherase reactions discussed above adenosylmethionine is cleaved by yeast (144) and bacterial enzymes (193) to
yield methylthioadenosine and 2-amino-4-butyrolactone. The mechanism
of this reaction may be viewed as a special case of nucleophilic substitution, for in this case it is the carboxyl oxygen of adenosylmethionine
itself which attacks the carbon atom adjacent to the positively charged
sulfur leading to displacement of the thioether, methylthioadenosine, and
to formation of the lactone. Alternatively, by consideration of the known
tendency of onium compounds to undergo elimination reactions, and by
analogy with the enzymatic cleavage of dimethylacetothetin to form
acrylic acid and dimethyl sulfide (111), it has been suggested that the
reaction might proceed with the formation of methylthioadenosine and
elimination of an olefin, 2-amino-3-butenoic acid, which might then form
2-amino-4-butyrolactone by a lactonization reaction for which there is
good biochemical precedent (194). Recently it has been shown experimentally (195) that with the yeast enzyme the enzymatic cleavage of
S-adenosylmethionine proceeds directly to the butyrolactone, rather than
with the formation of an olefin, thus establishing that the mechanism of
this reaction is by nucleophilic attack.
3. Alkyl Transfer and Base Exchange Reactions
As suggested in earlier publications (23, 100, 162) transmethylation
reactions may be considered as the simplest case of alkyl transfer reactions, for which the general formulation is Eq. 22.
R—CH 2 —B + H 2 X -* R—CH 2 —XH + B + ΗΘ
(22)
229
Thus, as noted in an earlier section, transalkylation reactions may be
viewed as nucleophilic substitutions in which there is attack upon one
of the carbons immediately adjacent to the positively charged sulfur.
The over-all result is displacement of a thioether from this carbon atom
synchronous with formation of a new bond between the same carbon
atom and the attacking reagent, the "acceptor." In the present case, the
nucleophilic attack may be spearheaded by a nitrogen, oxygen, or even
carbon atom of the acceptor molecule, and it may be forecast, from
what is known about transmethylation from other sulfonium compounds,
that compounds containing a sulfur atom will be likewise found capable
of attacking adenosylmethionine. In each case an enzyme specific for
the acceptor compound has been found and significant comparative data
are listed in Table VIII. It is interesting to note that the specific activities of the partially purified enzymes correlate pretty well with the
rates that could be expected on the basis of the physiological significance of the different reactions.
In addition to the alkylpherase reactions discussed above adenosylmethionine is cleaved by yeast (144) and bacterial enzymes (193) to
yield methylthioadenosine and 2-amino-4-butyrolactone. The mechanism
of this reaction may be viewed as a special case of nucleophilic substitution, for in this case it is the carboxyl oxygen of adenosylmethionine
itself which attacks the carbon atom adjacent to the positively charged
sulfur leading to displacement of the thioether, methylthioadenosine, and
to formation of the lactone. Alternatively, by consideration of the known
tendency of onium compounds to undergo elimination reactions, and by
analogy with the enzymatic cleavage of dimethylacetothetin to form
acrylic acid and dimethyl sulfide (111), it has been suggested that the
reaction might proceed with the formation of methylthioadenosine and
elimination of an olefin, 2-amino-3-butenoic acid, which might then form
2-amino-4-butyrolactone by a lactonization reaction for which there is
good biochemical precedent (194). Recently it has been shown experimentally (195) that with the yeast enzyme the enzymatic cleavage of
S-adenosylmethionine proceeds directly to the butyrolactone, rather than
with the formation of an olefin, thus establishing that the mechanism of
this reaction is by nucleophilic attack.
3. Alkyl Transfer and Base Exchange Reactions
As suggested in earlier publications (23, 100, 162) transmethylation
reactions may be considered as the simplest case of alkyl transfer reactions, for which the general formulation is Eq. 22.
R—CH 2 —B + H 2 X -* R—CH 2 —XH + B + ΗΘ
(22)