This study was designed to determine the possible mechanism by which orotic acid exerts its mitoinhibitory effect on rat hepatocytes in primary culture. Orotic acid inhibited, dose-dependently DNA synthesis in hepatocytes induced by epidermal growth factor, transforming growth factor alpha, hepatocyte growth factor, acidic fibroblast growth factor, or plasma from rats exposed to various liver c...

Recently orotic acid has been noticed as a growth factor and regarded as a pre cursor of nucleic acid (1, 2). But its distribution in organisms has scarcely been studied except for tracing the acid using C14-labeled compound (3). The authors have found that orotic acid shows a whitish blue primary fluorescence, which is re markably intensified by adding H2O2. Applying this property to histochem...

G. A. SANSING, E. B. LrLLEHOJ, R. W. DHROY and M. A. MILLER. Synergistic toxic effects of citrinin, ochratoxin A and penicillic acid in mice. Toxicoll 14, 213-220, 1976.-The LD50'S in mice of citrinin, ochratoxin A, and penicillic acid injected intraperitone,"lIy were 89,22, and 100 mg per kg of body weight, respectively. Paired combinations of the mycotoxins, citrinin: ochratoxin A (Cl:OA), oc...

By R. WAYNE RUNDLES AND SPENCER S. BREwER, JR. OROTIC ACID has become a compound of considerable metabolic interest in recent years since it appears to be a key intermediate in the synthesis of pyrimidines. It was discovered in the whey of cow’s milk by Biscara and Belloni in 1905, but its correct chemical structure was not established unfil 1930 by Bachstez.’2 Orotic acid has been isolated fro...

The effects of dietary food fortified with orotic acid (1.0%) on liver function were studied in rats. The rats fed with orotic acid promoted liver triglyceride content markedly, that was 5-fold higher than that of the control. The liver malondialdehyde (MDA) content increased by 10%, but the gluthation peroxidase (GSH-Px) activity decreased by 50%. The serum aspartate aminotransferase (AST) and...

Analogues of nucleic acid precursors were screened for antimalarial activity in Plasmodium knowlesi by using an in vitro culture system. Activity was assessed by the degree of inhibition of incorporation of l-[methyl-(14)C]methionine into protein and of [8-(14)C]adenosine and [6-(14)C]orotic acid into ribonucleic acid and deoxyribonucleic acid. The incorporation of adenosine or orotic acid was ...

Orotic acid is utilized by many mammalian and bacterial systems for the biosynthesis of the pyrimidines found in ribonucleic (UNA) and deoxyribonucleic (DNA) acids. 6-Uracil methyl sulfone (UMS) is one of several orotic acid analogs which have been synthesized and studied by Greenbaum, Hohnes, and Welch (1, 2, 15). Hohnes and Welch have shown (4) that UMS noncompetitively inhibits the growth of...

Incorporation of [3H]orotic acid into low-molecular-weight nRNA of rat liver, fractionated on polyacrylamide gels, increased 6-12h after partial hepatectomy and 6h after gamma-irridation at 2000 R. The incorporation of orotic acid was particularly increased into the 4.5S, 5S and approx. 10S nRNA fractions. If the irradiation was given after 6h of regeneration and RNA was isolated from the nucle...

Investigations of the metabolism of orotic acid have shown that this compound is utilized by cer thin bacteria (@O)and by the mammal for the syn thesis of pentosenucleic acid (1, 5). Although it has not been definitely established that orotic acid (or a metabolic derivative of it) is an obligatory inter mediate in the biosynthesis of nucleic acids, there is considerable evidence in support of t...

An improved method for the synthesis of N1-substituted orotic acid derivatives is reported. The method involves sequential incorporation of nitrogen atoms to the pyrimidine structure from simple starting materials and thus allows the synthesis of N1-substituted orotic acid derivatives with single 15N label at either N-1 or N-3.