206
G. L. CANTONI
added to the diet could serve as sources of "labile" methyl groups for
the rat and other vertebrates.* The ability to serve as dietary methyl
donors correlates well with the ability of these compounds to act as
sources of "mobile" methyl group in the enzymatic synthesis of
methionine (119, 120). Whether dimethylpropiothetin has a similar
function in the species in which it is found is not known. Nothing is
known about the biological origin or mechanism of formation of dimethylpropiothetin, but it might well arise by a reaction between
acrylyl-CoA and dimethylsulfide by analogy with the reaction between
acrylyl-CoA and ammonia discussed above (30). The chemical and
biochemical requirements for "methyl" group mobility and its relationship to "onium" configuration will be discussed in a later section.
2. S-Adenosylmethionine
S-Adenosylmethionine was discovered and identified by Cantoni
(121) as the product of the enzymatic activation of methionine for
transmethylation. It is formed enzymatically from methionine and
adenosine triphosphate in liver and other tissues (122), in yeast (123,
124), Escherichia colt (125), and probably a variety of other microorganisms, as well as in Chlorella (126, 127) and perhaps other green
algae, f
a. Chemistry. The structure of S-adenosylmethionine, first proposed
on the basis of biochemical evidence (121) and later confirmed both
by degradation (129) and by synthesis (130), is shown in Fig. 6.
* The term "labile methyl compound" as defined by du Vigneaud is a nutritional concept, in that it defines the ability of the compound to furnish "methyl
groups" for various synthetic reactions, when added to the diet. The increasing
complexity of our knowledge of transmethylation reactions and a fuller understanding of their mechanism requires some amplification of the terminology. Thus
it has been suggested (118) that a methyl, or alkyl, group directly attached to a
neutral onium pole be defined as "mobile methyl group" to indicate its high reactivity in enzymatic group-transfer reactions.
f The methionine-activating enzyme of liver and yeast will also utilize ethionine, and the selenium analog of methionine (128). The activation of ethionine
proceeds at a slower rate and the product is S-adenosylethionine, a compound with
chemical characteristics very similar to S-adenosylmethionine. Until it can be
shown that ethionine is a naturally occurring amino acid, S-adenosylethionine will
have to be considered as an analog of adenosylmethionine with potentially interesting features as an antimetabolite. Selenomethionine, on the other hand, is utilized
as well or better than methionine (128). The product Se-adenosylselenomethionine
can serve as a methyl donor biologically and satisfy the requirements for organic
selenium in the rat (128a). Since selenomethionine is a naturally occurring methionine analog it is probable that Se-adenosylselenomethionine is likewise a natural
product.
G. L. CANTONI
added to the diet could serve as sources of "labile" methyl groups for
the rat and other vertebrates.* The ability to serve as dietary methyl
donors correlates well with the ability of these compounds to act as
sources of "mobile" methyl group in the enzymatic synthesis of
methionine (119, 120). Whether dimethylpropiothetin has a similar
function in the species in which it is found is not known. Nothing is
known about the biological origin or mechanism of formation of dimethylpropiothetin, but it might well arise by a reaction between
acrylyl-CoA and dimethylsulfide by analogy with the reaction between
acrylyl-CoA and ammonia discussed above (30). The chemical and
biochemical requirements for "methyl" group mobility and its relationship to "onium" configuration will be discussed in a later section.
2. S-Adenosylmethionine
S-Adenosylmethionine was discovered and identified by Cantoni
(121) as the product of the enzymatic activation of methionine for
transmethylation. It is formed enzymatically from methionine and
adenosine triphosphate in liver and other tissues (122), in yeast (123,
124), Escherichia colt (125), and probably a variety of other microorganisms, as well as in Chlorella (126, 127) and perhaps other green
algae, f
a. Chemistry. The structure of S-adenosylmethionine, first proposed
on the basis of biochemical evidence (121) and later confirmed both
by degradation (129) and by synthesis (130), is shown in Fig. 6.
* The term "labile methyl compound" as defined by du Vigneaud is a nutritional concept, in that it defines the ability of the compound to furnish "methyl
groups" for various synthetic reactions, when added to the diet. The increasing
complexity of our knowledge of transmethylation reactions and a fuller understanding of their mechanism requires some amplification of the terminology. Thus
it has been suggested (118) that a methyl, or alkyl, group directly attached to a
neutral onium pole be defined as "mobile methyl group" to indicate its high reactivity in enzymatic group-transfer reactions.
f The methionine-activating enzyme of liver and yeast will also utilize ethionine, and the selenium analog of methionine (128). The activation of ethionine
proceeds at a slower rate and the product is S-adenosylethionine, a compound with
chemical characteristics very similar to S-adenosylmethionine. Until it can be
shown that ethionine is a naturally occurring amino acid, S-adenosylethionine will
have to be considered as an analog of adenosylmethionine with potentially interesting features as an antimetabolite. Selenomethionine, on the other hand, is utilized
as well or better than methionine (128). The product Se-adenosylselenomethionine
can serve as a methyl donor biologically and satisfy the requirements for organic
selenium in the rat (128a). Since selenomethionine is a naturally occurring methionine analog it is probable that Se-adenosylselenomethionine is likewise a natural
product.