This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Holmes, W. L. Articles by Welch, A. D. Search for Related Content PubMed PubMed Citation Articles by Holmes, W. L. Articles by Welch, A. D.

Biological Studies of Analogs of Orotic Acid: 6-Uracilsulfonic Acid, 6-Uracilsulfonamide, and 6-Uracil Methyl Sulfone^*

( Department of Pharmacology, School of Medicine, Yale University, New Haven, Conn.)

6-Uracilsulfonic acid was neither a growth factor nor an antagonist of the activity of orotic acid as a growth factor for Lactobacillus bulgaricus 09. However, in the presence of the sulfonic acid and uracil the strain which evolved had the capacity to utilize uracil in place of orotic acid.

Either 6-uracilsulfonamide or 6-uracil methyl sulfone noncompetitively inhibited the growth of L. bulgaricus 09 in a medium supplemented with orotic acid, whether the antagonist was added prior to inoculation of the medium or during the logarithmic phase of growth. The growth of the organism in the presence of DL-carbamylaspartate (ureidosuccinate), L-dihydroorotate, or uridine-5'-phosphate also was noncompetitively inhibited by the same antagonists, as was the orotic acid-supported growth of another strain (Hanson) of L. bulgaricus, and the growth of a variant of L. bulgaricus 09 (termed 09-X), which utilized uracil in lieu of orotic acid.

These antagonists inhibited the growth of Leuconostoc citrovorum (Pediococcus cerevisiae) (8081) and of Streptococcus faecalis (8043) only slightly at very high concentrations, but the response of the latter organism was more marked in the presence of pteroylglutamic acid than when it was grown on purines and thymine. Reversal of the effect of the antagonists on L. bulgaricus 09 was obtained with a material associated with samples of crude or partially purified ribonucleic acid (RNA) of yeast, and with alkaline or acid hydrolysates of the material, but not with highly purified samples of RNA of yeast or liver. The significance of the observations with the antagonists, with respect to their possible mechanisms of action, has been discussed.

^* This work was supported by a grant from the American Cancer Society upon recommendation of the Committee on Growth of the National Research Council. Presented in part before the Division of Biological Chemistry, 126th meeting of the American Chemical Society, New York, September, 1954.

Received 10/31/55.