244 UNITY AND DIVERSITY IN B lOCHEMISTK Y 



2. Proline y hydroxyproline 



The biosynthesis of proHne has been elucidated with the aid of strains 

 of E. coli which are specifically auxotrophic for proline. These strains fall 

 into two groups: those which accumulate glutamic y-semialdehyde and 

 those in which this substance can replace glutamic acid as a growth factor. 

 The reduction of glutamic acid to the semialdehyde is no doubt not so 

 simple as is indicated by the arrow in the scheme set out below. The 

 cyclization of proline would not require enzymic aid since y and S-amino- 

 aldehydes cyclize rapidly in neutral aqueous solution. 



NH, 

 ^"' ^ NHjCOCHjCHjCHCOOH 



ATP glutamine 



CH2 — Coj CH2 — CHa 



I .11. 



CHO CHCOOH ^ CH CHCOOH 



/ \/ 



NHa N 



glutamic y-semialdehyde J'-pyrroline— S-carboxylic acid 



\ 



Cri2 — CHj 



I I 



CH2 CHCOOH 



\/ 



NH 



proline 



Hydroxyproline is notably present in the connective tissue of animals. 

 In the latter, the use of isotopes has enabled it to be demonstrated that it 

 results from a modification of proline, which apparently is already present 

 since labelled hydroxyproline is not readily incorporated into the tissues. 



3. Ornithine, citrulline, arginine 



The formation of arginine from ornithine, via citrulline, has long been 

 known. In fact, the "ornithine cycle" of Krebs and Henseleit was one of the 

 first biosynthetic pathways ever proposed. 



The sequence ornithine-citrulline-arginine, first shown to occur in 

 mammalian liver, has been found in many other organisms [Neurospora, 

 Penicillium, E. coli, lactobacilli, animal tissues, etc.). 



The glutamate-ornithine relationship has been confirmed by the use of 

 isotopes and by the discovery of a Penicillium mutant responding to either 

 substance. 



