The molecular geometry of orotic acid was fully optimized using the gradient minimization technique. The computed geometrical parameters at the B3LYP/6-311G** level correspond well to those determined experimentally by X-ray diffraction. The relative stability of both the syn and anti conformations was investigated at the B3LYP/6-311G** level, where the syn-form was shown to be slightly more st...

A series of investigations using mutants of the fungus Neurospora has provided ample evidence that the pyrimidine orotic acid has a significant role in the biological synthesis of the ribose nucleosides uridine and cyti-dine.'-4 By use of isotopically labeled orotic acid several investigators5-8 have recently demonstrated that a similar conclusion may be drawn concerning a function of this pyri...

Hydroxyurea is thought to inhibit DNA synthesis but the site of inhibition has not been established. The urinary excretion of orotic acid was measured in 6 patients, 5 with acute leukemia and 1 with metastatic melanoma, receiving 6-azauridine which is known to inhibit orotidylic decarboxylase. The orotic aciduria observed in these patients was reversed by the addition of hydroxyurea, suggesting...

The pyrimidine analogs, 5-azaorotic acid (6 X 10@ M) and 5-azauracil (2 X 10@ M), caused approximately 50 per cent inhibition of the metabolism of orotic acid by cell free extracts from mouse liver or L5178Y leukemia cells. Seven other compounds of a total of 42 tested also caused at least 50 per cent inhibition at concentrations less than 2 X 10@ M. The primary site of action of the two symmet...

Other studies in this laboratory (1) drew our attention to the possibility that erotic acid might be concerned with the maintenance of adequate lactation in the rat and with the survival of the young. Since no data were available on the erotic acid content of milk, this study was undertaken. The occurrence of erotic acid as a component of milk has been indicated since 1904, when Biscaro and Bel...

1. The metabolism of 4-[4-14C]androstene-3,17-dione, 4-[4-14C]pregnene-3,20-dione, 5a-[4-14C]androstane-3a,17f8-diol, [4-4C]cholesterol, 7a-hydroxy4-6fi-3H]cholesten3-one, 5fi-[7fi-3H]cholestane-3a,7U-diol and [3H]lithocholic acid was studied in the microsomal fraction of livers from control and orotic acid-treated male rats. 2. As a result of the treatment the orotic acid-fed rats had fatty li...