5. ONIUM COMPOUNDS
217
originally thought to be a more complex cyclic structure with a molecular weight of 303 (Fig. 14,11) (160). Finally canaline, canavanine, and
2,4-diaminobutyric acid (shown in Fig. 14, III, IV, and V) contain a
4-carbon chain which may be derived directly from methionine. Both
canaline and canavanine are found in large amounts in the Jack bean
(161), and certain other plant materials (162), and 2,4-diaminobutyric
acid, known earlier as a constituent of the polymyxins antibiotic (163),
has been recently identified in rhizomes (164). It is thus tempting to
suggest that in all these cases the 4-carbon chain arises through an
enzymatic transalkylation reaction from one of the two naturally occurring sulfonium derivatives of methionine: S-methylmethionine or
S-adenosylmethionine.
V. Metabolism and Enzymology of Onium Compounds
As noted in a preceding section the biological activity of sulfonium
compounds was discovered in the course of investigations on the relationship between chemical structure and the biological ability to replace methionine for the biosynthesis of choline and other methylated
compounds. It was found in the course of these investigations that
betaine, dimethylacetothetin, dimethylpropiothetin, and S-methylmethionine can replace methionine as sources of methyl donors in the
adult rat. It will be immediately obvious that there is a clear-cut
chemical difference between methionine and the compounds in this
group in that these are all onium compounds whereas methionine itself
is a thioether. This chemical difference is reflected in the different biochemical behavior of these two types of methyl donor compounds.
Whereas an onium compound such as dimethylthetin can transfer one
of its methyl group to an acceptor compound without requiring a source
of energy, the transfer of the methyl group of methionine requires the
participation of ATP (55). This observation in turn led to the discovery
that in reality activation of methionine by ATP is a prerequisite to
methyl transfer and that as a result of this activation methionine is
transformed into a sulfonium compound which is characterized by the
ability to function as a methyl donor directly, that is, in the absence of
an energy source. Before discussing in more detail the enzymology of
onium compounds, the energetics of the onium bond will be reviewed.
A. ENERGETICS OF THE ONIUM BOND
(Written in collaboration with Dr. J. Durell)
The concept has been independently stated in recent years by several investigators (23, 162) that compounds with onium groups, par-
217
originally thought to be a more complex cyclic structure with a molecular weight of 303 (Fig. 14,11) (160). Finally canaline, canavanine, and
2,4-diaminobutyric acid (shown in Fig. 14, III, IV, and V) contain a
4-carbon chain which may be derived directly from methionine. Both
canaline and canavanine are found in large amounts in the Jack bean
(161), and certain other plant materials (162), and 2,4-diaminobutyric
acid, known earlier as a constituent of the polymyxins antibiotic (163),
has been recently identified in rhizomes (164). It is thus tempting to
suggest that in all these cases the 4-carbon chain arises through an
enzymatic transalkylation reaction from one of the two naturally occurring sulfonium derivatives of methionine: S-methylmethionine or
S-adenosylmethionine.
V. Metabolism and Enzymology of Onium Compounds
As noted in a preceding section the biological activity of sulfonium
compounds was discovered in the course of investigations on the relationship between chemical structure and the biological ability to replace methionine for the biosynthesis of choline and other methylated
compounds. It was found in the course of these investigations that
betaine, dimethylacetothetin, dimethylpropiothetin, and S-methylmethionine can replace methionine as sources of methyl donors in the
adult rat. It will be immediately obvious that there is a clear-cut
chemical difference between methionine and the compounds in this
group in that these are all onium compounds whereas methionine itself
is a thioether. This chemical difference is reflected in the different biochemical behavior of these two types of methyl donor compounds.
Whereas an onium compound such as dimethylthetin can transfer one
of its methyl group to an acceptor compound without requiring a source
of energy, the transfer of the methyl group of methionine requires the
participation of ATP (55). This observation in turn led to the discovery
that in reality activation of methionine by ATP is a prerequisite to
methyl transfer and that as a result of this activation methionine is
transformed into a sulfonium compound which is characterized by the
ability to function as a methyl donor directly, that is, in the absence of
an energy source. Before discussing in more detail the enzymology of
onium compounds, the energetics of the onium bond will be reviewed.
A. ENERGETICS OF THE ONIUM BOND
(Written in collaboration with Dr. J. Durell)
The concept has been independently stated in recent years by several investigators (23, 162) that compounds with onium groups, par-