5. ONIUM COMPOUNDS
221
nicotinamide lies between the values calculated for betaine and its sulfur
analog above: a value of —4 or —5 kcal, seems appropriate. This would
agree with the observation that the synthesis of N'-methylnicotinamide
from S-adenosylmethionine and nicotinamide is apparently irreversible
(174). However, this figure differs appreciably from the value of —9
kcal. (166, 175) for the free energy of hydrolysis of nicotinamide riboside. It seems unlikely that there is such a large difference in the energy
of hydrolysis of these analogous compounds. One possibility is that the
above argument for estimating the energy of hydrolysis of N'-methylnicotinamide is invalid. Another possibility is that the energy of hydrolysis of methionine differs appreciably from that of S-adenosylhomocysteine. If it were, for example, 4 kcal, instead of 8 kcal., the value for
AF'ds) would be —12.5 kcal., for AF' (17) would be —3 kcal., and the
estimated value for JV'-methylnicotinamide would be brought in line
with that for nicotinamide riboside. It can be shown, however, that such
a change in the estimated energy value for methionine hydrolysis would
have no effect on the calculation of AF\ 20) , which gives the free energy
of enzymatic synthesis of S-adenosylmethionine.
In conclusion, it appears that the above considerations confirm and
extend the earlier hypothesis that sulfonium compounds are energy-rich
in the same sense as "high-energy phosphate," i.e., they have a high free
energy of hydrolysis, in the order of —8 or —9 kcal. Quaternary ammonium compounds, on the other hand, are not energy-rich when one
considers the free energy of hydrolysis. They can transfer their methyl
groups to thiols, particularly homocysteine, by virtue of the "low-energy"
level of thioethers, i.e., the positive energy of hydrolysis of thioethers.
The difference in stability of these two types of methyl-onium compounds parallels the difference in basicity of thioethers and tertiary
amines. The relative position of aromatic quaternary ammonium compounds is not definitely established, but it appears that they lie between
sulfonium and aliphatic quaternary ammonium compounds, perhaps
closer to the former.
B. TRANSFER REACTIONS FROM AN ONIUM POLE
1. Methyl Transfer from Dimethylacetothetin and Betaine
An enzyme capable of transferring one of the methyl groups of dimethylacetothetin and/or betaine to homocysteine was first recognized
by Borsook and Dubnoff (55, 176) in mammalian liver and kidney, and
has been further studied by Durell, Anderson and Cantoni (119) in
horse liver, by Maw (120) and by Fromm (177) in rat liver, by Sloane
221
nicotinamide lies between the values calculated for betaine and its sulfur
analog above: a value of —4 or —5 kcal, seems appropriate. This would
agree with the observation that the synthesis of N'-methylnicotinamide
from S-adenosylmethionine and nicotinamide is apparently irreversible
(174). However, this figure differs appreciably from the value of —9
kcal. (166, 175) for the free energy of hydrolysis of nicotinamide riboside. It seems unlikely that there is such a large difference in the energy
of hydrolysis of these analogous compounds. One possibility is that the
above argument for estimating the energy of hydrolysis of N'-methylnicotinamide is invalid. Another possibility is that the energy of hydrolysis of methionine differs appreciably from that of S-adenosylhomocysteine. If it were, for example, 4 kcal, instead of 8 kcal., the value for
AF'ds) would be —12.5 kcal., for AF' (17) would be —3 kcal., and the
estimated value for JV'-methylnicotinamide would be brought in line
with that for nicotinamide riboside. It can be shown, however, that such
a change in the estimated energy value for methionine hydrolysis would
have no effect on the calculation of AF\ 20) , which gives the free energy
of enzymatic synthesis of S-adenosylmethionine.
In conclusion, it appears that the above considerations confirm and
extend the earlier hypothesis that sulfonium compounds are energy-rich
in the same sense as "high-energy phosphate," i.e., they have a high free
energy of hydrolysis, in the order of —8 or —9 kcal. Quaternary ammonium compounds, on the other hand, are not energy-rich when one
considers the free energy of hydrolysis. They can transfer their methyl
groups to thiols, particularly homocysteine, by virtue of the "low-energy"
level of thioethers, i.e., the positive energy of hydrolysis of thioethers.
The difference in stability of these two types of methyl-onium compounds parallels the difference in basicity of thioethers and tertiary
amines. The relative position of aromatic quaternary ammonium compounds is not definitely established, but it appears that they lie between
sulfonium and aliphatic quaternary ammonium compounds, perhaps
closer to the former.
B. TRANSFER REACTIONS FROM AN ONIUM POLE
1. Methyl Transfer from Dimethylacetothetin and Betaine
An enzyme capable of transferring one of the methyl groups of dimethylacetothetin and/or betaine to homocysteine was first recognized
by Borsook and Dubnoff (55, 176) in mammalian liver and kidney, and
has been further studied by Durell, Anderson and Cantoni (119) in
horse liver, by Maw (120) and by Fromm (177) in rat liver, by Sloane