Abstract

Dietary protein depletion results in a decrease in rat hepatic xanthine oxidase activity to about 10% of control levels. Refeeding of a high protein diet leads, after a 6-hour lag phase, to a 5-fold increase in enzyme activity by 12 hours. The mechanism of this increase was studied utilizing actinomycin D, 5-fluorouracil, and puromycin. These agents all blocked the increase in enzyme activity, indicating that both ribonucleic acid and protein syntheses were involved. Following administration of 14C-leucine, specific radioactivities of xanthine oxidase were identical in the livers of protein-depleted and control animals, despite a 10-fold difference in enzyme activity levels. These results indicated that the fractional turnover rates were the same in the two groups of rats and suggested that the rate of xanthine oxidase synthesis was reduced 10-fold in the depleted rats prior to protein re-feeding. Greatly increased isotopic labeling of highly purified enzyme with 14C-leucine during the phase of restoration of enzyme levels indicated that the increase in activity was the result of accelerated apoenzyme synthesis de novo.

Highlights

  • Refeeding of a 23% protein diet resulted in a rise of activity to levels about 55% of control levels in 12 hours

  • There was an initial 6-hour lag period followed by a rapid rise between 6 and

  • RNA, was evaluated. 5-Fluorouracil was given intraperitoneally in a dose of 50 mg hourly, commencing at the time of refeeding, according to the technique of Garen et al, and its administration was associated with a complete inhibition of the usual rise of enzyme activity found at 12 hours after refeeding. These results indicated that the rise of xanthine oxidase activity associated with refeeding is dependent upon new RNA

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Summary

Methods

Female Osborne Mendel rats, 10 to 11 weeks old, weighing 170 to 200 g, were used in all experiments. These animals had been maintained exclusively on standard Purina rat chow (23% protein) from weaning. The rats were housed five to a cage, and for 14 days each received approximately 14 g of 8% low protein diet. The diet contains salt mixture USP XIV and Vitamin Diet Fortification Mixture (Nutritional Biochemicals). On this regimen the animals gained 5 to 10% of their original weight over 14 days compared with a 10 to 15% gain for control animals maintained on standard Purina rat chow. Refeeding was carried out with Purina rat Studies on Xanthine Oxidase

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