IV BIOSYNTHESIS OF AMINO ACIDS 73 



that aspartyl-CoA is an intermediate in homoserine synthesis by E. coli. Pyridoxal phosphate 

 and ATP are required in the conversion of homoserine to threonine. The activation of 

 homoserine may therefore precede the utihzation of this substance. 



The relationship between aspartate and threonine in E. coli and in yeast cells 

 is supported by isotope experiments. It has been observed that when these 

 organisms are grown in the presence of pyruvate-2-''*C or labelled acetate, the 

 distribution of label in threonine corresponded to that in aspartate as predicted 

 by the above pathway (Wang et al., 1955). 



The conversion of homoserine to methionine 



Cystathionine and homocysteine are intermediates in the formation of methionine 

 from homoserine. Experiments by Horowitz showed that a Neurospora mutant 

 which required methionine and could respond to homocysteine accumulated 

 cystathionine in the mycelium while another mtitant responded only to methionine. 

 A third mutant, blocked earlier in the biosynthetic sequence, responded to cysteine 

 as well as to methionine, homocysteine, or cystathionine (Horowitz, 1947). A 

 series of mtitants with similar nutritional requirements were found in E. coli. 



Cystathionine is probably formed by a condensation of homoserine with cysteine. The 

 cystathionine may then be cleaved to homocysteine and serine. Evidence for the reverse 

 of these reactions has already been described in connection with the formation by animal 

 tissues of cysteine from methionine and homocysteine (Binkley and Okeson, 1950; Rachele 

 et al., 1950; Tabachnick and Tarver, 1955). 



Methionine formation from homocysteine 



Neogenesis of jnethyl groups. The following substances are potential precursors 

 of the methyl groups of methionine : formate, formaldehyde, the beta carbon of 

 serine, the alpha carbon of glycine, the methyl groups of sarcosine, and dimethyd- 

 glycine (McKenzie and Abeles, 1956). Vitamin Bjj and folic acid are required 

 for the neogenesis of methyl groups from these substances (Johnson et al., 1955). 

 The conversion of formate-''*C or serine-3-^'^C to methionine or choline methyl 

 groups is increased in weanling rats when cobalamine and homocysteine is added 

 to the diet (Arnstein and Neuberger, 1953). The conversion of serine-3-^"*G or 

 Hz^'^CO and homocysteine to methionine has been demonstrated at the enzyme 

 level with sheep liver extracts (Nakao and Greenberg, 1955). Leucovorin, ATP, 

 Mg"^"^ and DPN^ stimulate the conversion w^hile deoxypyridoxine inhibits methionine 

 synthesis. The inhibition is partially reversed by pyridoxal phosphate. 



The methyl groups of dimethylglycine and sarcosine, are probably oxidized 

 to the level of formaldehyde before being used for the synthesis of the methyl 

 groups of methionine or choline (McKenzie and Abeles, 1956). When sarcosine, 

 completely labeled with deuterium in the methyl group, was incubated with liver 

 mitochondria, it was observed that the beta carbon of serine and free formaldehyde 

 contained deuterium having the same atom per cent excess as the substrate. The 

 conversion of the beta carbon of serine to the methyl groups of choline and thymine 

 without loss of its bonded hydrogen atoms has also been demonstrated (Elwyn 

 et al., 1955). These conversions may be schematically represented as follows: 



Literature p. 124 



