78 INTERMEDIARY METABOLISM AND GROWTH I 



diaminopimelic acid to lysine (Fig. 35). This enzyme is lacking in diose lysine 

 auxotrophs of E. coli which accumulate diaminopimelic acid. Lysine requiring 

 mutants of JVeurospora do not respond to diaminopimelic acid nor do E. coli mutants 

 respond to a-aminoadipic acid (Dewey and Work, 1952; Davis, 1952). 



Although aspartate does not seem to be a direct aminoadipic acid precursor in inolds, 

 it would seem that a closer relationship exists between lysine biosynthesis and aspartate 

 in bacteria. Non-labelled aspartate reduces the conversion of glucose- '-"C to lysine in E. coli 

 (Abelson, 1954). Certain incompletely blocked diaminopimelic mutants can respond to 

 threonine, diaminopimelic, or lysine (Davis, 1952), but not to aspartate. Aspartic, aspara- 

 gine, proline, tyrosine, pyridoxal, inositol, and choline can substitute for the lysine re- 

 quirements of Streptococcus faecalis (6057) (McClure et al., 1954). On the other hand, 

 lysine and threonine can spare aspartic acid in those Lactobacillus arabinosus cells whose 

 growth is inhibited by the antimetabolite of aspartate, cysteic acid (Ravel et al., 1954). 



{h) Glutamic family : Glutamic, proline, hydroxyproline, arginine 



Glutamic. The formation of glutamic acid from a-ketogiutarate and aspartate is 

 catalyzed by the enzyme, transaminase. Glutamic acid may also be formed by the 

 reductive amination of a-ketoglutarate (reactions i and 2) or as a result of the 

 catabolism of histidine, proline, arginine, and ornithine. 



transaminase 

 i) Aspartic + a-ketoglutaric ' ^ glutamic + oxalacetic 



glutamic dehydrogenase 

 2) a-Ketoglutaric + TPNH2 + NHj ' . glutamic + TPN"" 



Proline. Glutamic-^''C is a precursor of both the proline and arginine of rat or 

 Meurospora protein (Stetten, 1955; Abelson, 1954). Glutamic-y-semialdehyde 

 reduces the incorporation of labelled glucose into proline. An enzyme which 

 catalyzes the reduction of glutamic to glutamic semialdehyde exists in Neurospora. 

 Glutamic semialdehyde spontaneously cyclizes to Ai-pyrroline-5-carl:)Oxylate 

 which can be reduced to proline (Yura and Vogel, 1955) (Fig. 36). In the presence 

 of glutamate, a mutant strain of E. coli accumulates pyrroline carboxylate 

 (Strecker and Mela, 1955). 



Ornithine is also a proline precursor in mammals, fungi and bacteria. When 

 ornithine labelled with '^N on the a-amino group was fed to mice, the pro- 

 line, hydroxyproline, glutamate, and aspartate of the proteins contained isotopic 

 nitrogen (Stetten, 1 95 1 ) . The gamma N of ornithine contributed to a greater degree 

 to glutamic acid than to proline. Ornithine labelled with deuterium was also con- 

 verted to proline and to glutamate in mice. The loss of the terminal amino group 

 from ornithine would result in the formation of glutamic semialdehyde, the 

 proline precursor. An enzyme which catalyzes the formation of glutamic semialde- 

 hyde from ornithine occurs in mammalian liver preparations and in fungi (Meister, 

 1954; Fincham and Boulter, 1956, Fig. 36). Some ornithine-^'*C is also incorpo- 

 rated into the proline, glutamate, and arginine of £■. coli protein (Vogel, 1956) 

 by the metabolic pathway shown above. However, this metabolic link appears to 

 be relatively unimportant in this organism. 



Hydroxyproline. The feeding of proline-'^N to rats results in the labelling of the 

 hydroxyproline of the rat proteins (Stetten, 1949). The reverse reaction does not 



