218
G. L. CANTONI
ticularly quaternary ammonium and sulfonium compounds, serve biologically as a source of utilizable chemical energy analogous to compounds with pyrophosphate and acyl phosphate linkages. The concept
evolved independently from two different lines of research: (a) the
study of base exchange reactions, particularly the thiaminase reaction
(165); and (b) the study of transmethylation reactions (23). In the
first case, it was observed that a number of nitrogenous bases could
exchange for the thiazolium moiety of thiamine, thus indicating that
this onium compound served as the source of energy for synthetic reactions. Moreover, it appeared that the reaction was irreversible unless
the new linkage formed also resulted in the formation of an onium
group. In the area of transmethylation, with the discovery of S-adenosylmethionine (121), it became apparent that compounds acting as
donors of mobile methyl groups were invariably methyl-onium compounds, again pointing to the utilization of the energy of the onium
group for chemical synthesis. The concept that the driving energy for
these reactions resided in the reduction of the onium pole was elaborated by Woolley (162). Both Cantoni (23) and Kalckar (166) considered it more important to stress the significance of the liberation of
a proton in a buffered solution. The two explanations differ only formally, because the liberation of a proton in aqueous solution results in
the formation of a hydronium ion, and the reaction of this ion with
buffer can, if one wishes, be viewed as the reduction of an onium group
and the oxidation of the buffer.
Any discussion of the energetics of transmethylation is necessarily
handicapped by the unfortunate fact that no equilibrium measurements
have been obtained on any transmethylation reaction. It has been possible, however, to determine calorimetrically the enthalpy change associated with two transmethylation reactions catalyzed by purified
thetin-homocysteine methylpherase (119). With certain reasonable assumptions as to the entropy changes involved, the free energy changes
of these reactions have been estimated. The first of these is Reaction
13.*
CH3
CH3 H
CH3
CH3
S
+S-+S+S
+ΗΘ
(13)
I
I
I
I
R
1
R
2
R
1
R
2
* Throughout this section, the symbols R
1 and R
2 have the following meanings:
R
1 = — CH2COOR
2 = — CH 2 CH 2 CHNH 3 COO-
G. L. CANTONI
ticularly quaternary ammonium and sulfonium compounds, serve biologically as a source of utilizable chemical energy analogous to compounds with pyrophosphate and acyl phosphate linkages. The concept
evolved independently from two different lines of research: (a) the
study of base exchange reactions, particularly the thiaminase reaction
(165); and (b) the study of transmethylation reactions (23). In the
first case, it was observed that a number of nitrogenous bases could
exchange for the thiazolium moiety of thiamine, thus indicating that
this onium compound served as the source of energy for synthetic reactions. Moreover, it appeared that the reaction was irreversible unless
the new linkage formed also resulted in the formation of an onium
group. In the area of transmethylation, with the discovery of S-adenosylmethionine (121), it became apparent that compounds acting as
donors of mobile methyl groups were invariably methyl-onium compounds, again pointing to the utilization of the energy of the onium
group for chemical synthesis. The concept that the driving energy for
these reactions resided in the reduction of the onium pole was elaborated by Woolley (162). Both Cantoni (23) and Kalckar (166) considered it more important to stress the significance of the liberation of
a proton in a buffered solution. The two explanations differ only formally, because the liberation of a proton in aqueous solution results in
the formation of a hydronium ion, and the reaction of this ion with
buffer can, if one wishes, be viewed as the reduction of an onium group
and the oxidation of the buffer.
Any discussion of the energetics of transmethylation is necessarily
handicapped by the unfortunate fact that no equilibrium measurements
have been obtained on any transmethylation reaction. It has been possible, however, to determine calorimetrically the enthalpy change associated with two transmethylation reactions catalyzed by purified
thetin-homocysteine methylpherase (119). With certain reasonable assumptions as to the entropy changes involved, the free energy changes
of these reactions have been estimated. The first of these is Reaction
13.*
CH3
CH3 H
CH3
CH3
S
+S-+S+S
+ΗΘ
(13)
I
I
I
I
R
1
R
2
R
1
R
2
* Throughout this section, the symbols R
1 and R
2 have the following meanings:
R
1 = — CH2COOR
2 = — CH 2 CH 2 CHNH 3 COO-