Biochemistry of Amino Acids - A. Meister 1961

The Role of Amino Acids in Nutrition
Amino Acid Antagonists
Methionine Antagonists

The Study of a synthetic amino acid antimetabolite was first conducted by Dyer in 1938. She synthesized ethionine — an S-ethyl analogue of Methionine — and established that this compound does not replace methionine, which is essential for rat growth.

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Dyer also noted that when fed ethionine, rats lost weight more rapidly than when methionine was completely excluded from their diet, and this effect of ethionine was mitigated by the simultaneous administration of methionine [223]. Dyer's observations have been repeatedly confirmed; furthermore, it has been established that ethionine inhibits the growth of microorganisms [217, 220]. In rats, ethionine inhibits the incorporation of Glycine and methionine sulfur into body Proteins, as well as The conversion of methionine into cystine [221]. In female rats, the administration of large amounts of ethionine soon causes Fatty Liver degeneration; this disorder is reversed by the administration of methionine, but cannot be alleviated by A number of Other Amino Acids studied [226]. Ethionine inhibits The transfer of the methionine methyl group to Choline in rats, but does not affect The formation of creatine [222]. Interestingly, choline, like methionine, exerts a beneficial effect in ethionine intoxication [224]. Following the administration to rats of ethionine labeled with C¹⁴ in the methylene carbon of the ethyl group, a significant amount of the radioactive isotope was detected in the trimethylamine residue of choline. The carbon of the ethyl group was also incorporated into creatinine; in addition, the sulfur of ethionine was converted into cystine [225]. It is quite evident that ethionine undergoes transformations in the rat Organism. It has been suggested that its toxic effect is due to the formation of ethyl analogues of choline and Other Compounds [274, 275]. This hypothesis is supported by data showing that triethylcholine suppresses rat growth [225] and inhibits acetylcholine synthesis in mice [227]; The Effect of triethylcholine is partially reversed by choline. Experiments with ethionine labeled in the methylene carbon of the ethyl group have further demonstrated that the ethyl group carbon is incorporated into proteins; several authors emphasize that this results in the formation of proteins differing from normal ones [207, 228, 229, 274]. The administration of ethionine to rats decreases The activity of the choline oxidase and Sarcosine oxidase enzyme systems [230] and increases the concentrations of Certain amino acids in the liver [231]. The Toxic Effect of ethionine may be due either to the conversion of essential metabolites into the corresponding ethyl analogues, or to the formation of proteins in which methionine is replaced by ethionine, or to both of these factors (p. 277). Ethionine undergoes, at least in part, the same transformations as methionine. Thus, for example, when cultivating Torula utilis and Saccharomyces cerevisiae in a medium containing ethionine, the formation of 5'-ethylthioadenosine was observed [276].

It has been found that DL-selenomethionine, СН₃SеСН₂СН₂СНNН₂СООН, acts as a competitive antagonist of L- and D-methionine, inhibiting the growth of Chlorella vulgaris [295]. The toxicity of this selenium analogue is reversed by methionine, which apparently prevents the uptake of the antagonist by the Cells. Selenate salts are active antimetabolites themselves and appear capable of being converted into Organic compounds within algal cells.

Other methionine antagonists include 2-amino-5-heptenoic acid (a vinyl analogue of methionine), methoxinine (an oxygen analogue), methionine sulfoximine, and norleucine.

2-Amino-5-heptenoic acid inhibits the growth of one Escherichia coli strain, but does not cause inhibition in two other strains or in Yeast [216]. The bacteriostatic effect of DL-methoxinine on E. coli and Staphylococcus aureus can be reversed by L-methionine, but is not alleviated by its D-isomer [217]. Methionine sulfoximine (see formula on p. 147) acts as a potent antimetabolite of glutamic acid [197, 198] and methionine [232]. This antimetabolite is formed during the Treatment of wheat flour with nitrogen trichloride ("agene") As a result of the bleaching agent's action on flour proteins. Methionine sulfoximine, much like agene-treated flour, induces a condition in dogs known as "canine hysteria" or "running fit seizures"; it also exerts a toxic effect on other animals. Definitive data on the effects of methionine sulfoximine on humans are lacking; nevertheless, measures have been taken to ban The Use of nitrogen trichloride in food Processing.