Metabolism of Deoxyuridine in Rabbit Brain

Abstract: The metabolism of ³H]deoxyuridine by rabbit brain was investigated in vitro and in vivo . In vitro , brain slices from various regions of brain and from all age groups accumulated ³H]deoxyuridine from artificial CSF. Within the slices, a portion of the accumulated ³H]deoxyuridine was metabolized to ³H]deoxyuridine phosphate, with subsequent conversion to ³H]thymidine phosphate, and ultimately ³H]DNA. The percentage of the ³H]deoxyuridine phosphorylated and subsequently converted into ³H]DNA was highest at birth and declined to adult levels in 3-month-old rabbits. Thymidine, when added to the incubation medium with the ³H]deoxyuridine, was approximately 10 times as potent as unlabeled deoxyuridine in inhibiting the intracellular phosphorylation and conversion of ³H]deoxyuridine to ³H]thymidine phosphate in brain slices. In vivo , 2.5 h after intraventricular injection of ³H]deoxyuridine, over 90% of the ³H]deoxyuridine was cleared from the central nervous system at all ages. However, in both newborn and 3-month-old rabbits, approximately 40 and 12%, respectively, of the ³H remaining in brain was phosphorylated and converted to ³H]thymidine phosphates; and 11 and 4%, respectively, of the ³H remaining in brain was converted to ³H]DNA. These results show that both immature and mature rabbit brain is able to incorporate deoxyuridine into DNA. Thus, all the enzymes involved in this conversion, including thymidylate synthetase (EC 2.1.1.45), are present and active in brain throughout life.