VOL. 12 (1953) BIOCHIMICA ET BIOPHYSICA ACTA 223 



ENZYMIC SYNTHESIS AND 

 BREAKDOWN OF A PYRIMIDINE. OROTIC ACID 



I. DIHYDRO-OROTIC DEHYDROGENASE 



by 



IRVING LIEBERMAN* and ARTHUR KORNBERG 



National Institutes of Health, Bethesda, Maryland and The Department of Microbiology, 

 Washington University School of Medicine, St. Louis, Missouri {U.S. A .) 



Orotic acid (4-carboxyuracil) was first isolated from cow's milk^ and has since been 

 observed to be a growth factor for Neurospora mutants^ and bacteria^"', and to be ac- 

 cumulated in large amounts by some mutant strains of Neurospora^. Recent experiments 

 with intact rats^~^^, rat liver slices^^' ^^, and growing cultures of Lactobacillus bulgaricus 

 ogi^ have provided evidence that orotic acid, or a compound metabolically related to it, 

 is a precursor of nucleic acid pyrimidines. Of great interest is the finding that ureido- 

 succinic acid (USA) can partially replace the orotic acid requirement of L. bulgaricus and 

 that ^^C-labelled USA like orotic acid is incorporated with relatively little dilution into 

 the pyrimidine nucleotides of the growing bacteria^*. 



In order to obtain some definitive information about the pathways of orotic acid 

 breakdown and clues to the mechanism of its biosynthesis, a bacterial organism was 

 isolated by enrichment culture which was able to metabolize this compound rapidly. 

 With enzyme preparations derived from this organism, evidence has been obtained to 

 support the following scheme for orotic acid breakdown and synthesis^^ : 



(i) HN— C = O HN— C = O 



O = C CH + DPNH + H+ ^ O = C CHg + DPN 

 HN— C HN— CH 



(2) 



* Aided by a Fellowship froin The National Foundation for Infantile Paralysis. 

 References p. 234. 



