NUCLEOTIDES I39 



guanine and adenine but not into uracil orcytosine. Further- 

 more, although carbon from isotopically labelled lactate was 

 found in both types of compound, the resultant distribution 

 of the isotope suggests that it entered the pyrimidines via 

 oxaloacetate, and the purines via glycine [20]. Certain pyri- 

 midine auxotrophs of Neurospora grow much better on 

 uridine or cytidine than on the free bases, and this again 

 suggests that the latter are not natural intermediates in 

 nucleoside synthesis. Some of the mutants used orotic acid 

 (uracil-6-carboxylic acid) to the same extent as uracil 

 itself [32], whilst others, for which this replacement was 

 not possible, accumulated orotic acid in the medium [39]. 

 Though oxaloacetate, aminofumarate and aminofumaric 

 acid diamide supported the growth of two of the mutants, 

 they were only one tenth as effective as uracil. These and 

 other observations led Houlahan and Mitchell to propose 

 that in Neurospora, the biosynthetic sequence was: oxalo- 

 acetate — >- a-A^-pentosylaminofumaric acid diamide — >- 

 A — > B — > pyrimidine nucleoside: they also suggested that 

 orotic acid is not a true intermediate but is related to the 

 precursors A and B. In this connection it is interesting to 

 note that a glycoside of orotic acid, probably the riboside, 

 has been isolated from the mycelium of a uridine requiring 

 mutant of Neurospora, and it is possible that this substance 

 is a natural intermediate [43]. Incubation of Sac. cerevisiae 

 with isotopically labelled orotic acid results in the appear- 

 ance of the isotope in the uracil, but not the guanine, of the 

 nucleic acids. Orotic acid has also been implicated in the 

 synthesis of pyrimidines by streptococci, Lh. casei and Lh. 

 bulgaricus [16]; the orotic acid requirements of the latter 

 organism can be replaced by ureidosuccinic acid, a sub- 

 stance related to aminofumaric acid [56]. 



Synthesis of deoxyribose, ribose, nucleosides and nucleotides 



A partially purified preparation of an aldolase obtained 

 from Esch. coli has been shown to condense glyceraldehyde- 

 3 -phosphate with acetaldehyde and thus form deoxyribose- 

 5-phosphate, which is converted by an isomerase, present 

 in crude extracts, to deoxyribose- 1 -phosphate [44]. Whilst 



