IV BIOSYNTHESIS OF AMINO ACIDS 75 



The latter substance was isolated after a purified enzyme preparation was incu- 

 bated with methionine and ATP. With methionine-^^S or with methionine-2- 

 ^''C as substrate, radioactivity was found in S-adenosyl methionine. 



A soluble enzyme of liver catalyzes the transfer of the methyl group of S- 

 adenosyl methionine to nicotinamide or to guanidoacetic acid (Cantoni and 

 Vignos, 1954; Fig. 32). S-adenosylhomocysteine, the product of the above reaction, 

 mav then be hvdrolvzed to adenosine and homocysteine. 



Ethanolamine 



Guanidoacetic 



Noradrenaline 



Anserine 



Nicotinamide 



ATP 



Dimetlnylglycine^ ^Methionine ^S-Adenosylmethionine 



^ - H O 

 Betaine aldehyde »-Betaine-^ 'Homocysteine— S-Adenosy I homocysteine' 



/ 



Choline - -I Choline 



Creatine 



Adrenaline 

 Carnosine 

 N-Methylnicotinamide 



Fig. 32. Transmethylase reactions. 



Adenosine thiomethylriboside, a compound related to S-adenosylmethionine, 

 is accumulated by yeast cells when methionine is added to the culture medium 

 (Schlenk and Smith, 1953). Methionine doubly labelled with -^^S and with '"^C 

 in the S-methyl group of the molecule is incorporated into adenosine thiomethyl 

 riboside. The latter substance is probably formed by hydrolysis of S-adenosyl- 

 methionine : 



H2O 



S-adenosylmethionine * homoserine + adenosine thiomethylriboside 



The fact that thiomethyladenosine can be utilized by yeast cells for the synthesis of 

 methionine emphasizes the close relationship between these compounds. How- 

 ever, in the transmethylase system of liver which functions in the synthesis of 

 methionine, homocysteine rather than S-adenosylhomocysteine is the substrate (Ericson 

 etal., 1955a). S-adenosylhomocysteine is only 40% as effective as homocysteine as 

 a substrate in this reaction (Ericson et al., 1955b) in crude enzyme systems and has 

 negligible activity in the purified enzyme system. The crude enzyme extracts are 

 capable of cleaving S-adenosylhomocysteine to homocysteine and adenosine (Fig. 

 32). 



Homoserine to cc-ketobutyric 



As mentioned earlier, the biosynthesis of isoleucine by microorganisms involves 

 the condensation of acetaldehyde and a-ketobutyrate to a six carbon com- 

 pound which by pinacol rearrangement is converted to the isoleucine precursors. 

 Methionine and homoserine are potential precursors of the a-ketobutyrate re- 

 quired for isoleucine synthesis. DL-methionine-2-''*C can also be converted to 

 homoserine and to a-aminobutyric acid in animal tissues (Matsuo and Greenberg, 



Literature p. 124 



