Purine metabolism in high and low uric acid lines of chickens: phosphoribosylpyrophosphate (PRPP) synthetase activities and PRPP pool sizes.

Abstract

Phosphoribosylpyrophosphate synthetase activities were examined in liver and kidney tissues of two genetic lines of chickens selected for their plasma uric acid levels. Previous work demonstrated that the high uric acid line (HUA) has significantly greater de novo uric acid synthesis rates in kidney tissue compared to the low uric acid line (LUA). In addition, xanthine dehydrogenase activity in liver and kidney tissues was significantly higher in the HUA compared to the LUA line. The activity of PRPP synthetase, which provides a key substrate for the rate limiting step in de novo purine biosynthesis, was found to be significantly elevated (P less than 0.05) in liver and kidney tissues of the HUA line. The mean value of kidney PRPP synthetase activity was 30.2 +/- 0.7 nmole PRPP and 19.1 +/- 1.6 nmol PRPP produced/mg protein/hr, respectively, for the HUA and LUA lines. The PRPP pool size in kidney tissue was also significantly higher in the HUA line. The mean level of PRPP was 319.8 +/- 37.2 pmole/g of wet tissue compared to 176.7 +/- 12.4 pmole PRPP/g of wet tissue in the LUA line. The mean values of liver PRPP synthetase activities were 11.4 +/- 0.6 nmole PRPP and 9.0 +/- 0.4 nmole PRPP produced/mg protein/hr, respectively, for the HUA and LUA lines. The PRPP pool size in liver tissues was significantly higher in the HUA line as well. The mean level of PRPP was 550.7 +/- 72.5 pmole/g of wet tissue compared to 313.6 +/- 31.4 pmole PRPP/g of wet tissue in the LUA line. The enzyme from the HUA birds does not differ from controls with respect to Michaelis constants, inhibition phenomena, and phosphate activation. The increased PRPP synthetase activity found in HUA tissues may be due to structural alterations of the molecule resulting in an enzyme with a greater Vmax, an increase in the amount of enzyme protein, or a lowered level of a nondialyzable inhibitor.