74 



INTERMEDIARY METABOLISM AND GROWTH 



glycine 



-^ serine-CDzOH 



H 



Sarcosine-CDs — j-^ f^CDz) > choline-CD2H 



i 



D 



CD2O 



-» thymine-CDzH 



It is possible that S-hydroxymethylmethionine is an intermediate in the syn- 

 thesis of methionine from homocysteine and "formaldehyde". Consistent with 

 this hypothesis is the fact that when methionine-S-^'*CH,OH is administered to 

 rats, radioactivity is observed in the methyl group of the methionine (Stekol, 1954). 



Betaine tiansmethylase. In the presence of the enzyme, transmethylase, one methyl 

 group of betaine may be transferred directly to homocysteine: 



Betaine + homocysteine -^ methionine + dimethylglycine 



In 1939, Du Vigneaud showed that betaine perinitted growth of rats with homo- 

 cysteine as the only sulfur containing amino acid. Choline which was also active 

 in this respect, was active by virtue of the fact that it could be converted to betaine 

 (Du Vigneaud, 1952). Only organisms possessing an active choline oxidase could 

 utilize choline instead of betaine as a methyl donor for methionine synthesis. 

 Choline, which serves as a methyl donor in crude liver enzyme systems only under 

 aerobic conditions is converted to dimethylglycine and not to dimethylethanol- 

 amine when incubated with homocysteine and rat liver homogenates. The be- 

 taine-homocysteine transmethylase enzyine has been purified from rat and pig liver 

 (Ericson et al., 1955a). 



Methyl group transfer from methionine 



The methyl group of methionine is also utilized in transmethylation reactions 

 for the synthesis of the methyl groups of choline, creatine, and other methylated 

 compounds. These transmethylation reactions are not inhibited in animals lacking 

 adequate vitamin Bjj or folic acid. As in the case of betaine, the methyl group of 

 methionine is transferred as a unit, without loss of bonded hydrogen atoms (Du 

 Vigneaud et al., 1956). However, the methionine must be activated prior to methyl 

 group transfer (Cantoni and Vignos, 1954). Evidence has been presented that 

 active methionine is identical with S-adenosyl methionine (Cantoni, 1953; Fig.31). 



NH 



CH— CHOH — CHOH — CH — CH2— S — CH^— CHj— CH— COO' 



-O- 



' '^^2 



Fig. 31. S-Adenosylmethionine. 



NH, 



