Elevated AMP pyrophosphorylase activity in congenital IMP pyrophosphorylase deficiency (Lesch-Nyhan disease)

The decay of IMP pyrophosphorylase (HGPRTase) and AMP pyrophosphorylase (APRTase) in the erythrocytes of normal and IMP pyrophosphorylase-deficient children has been studied. In normal children, the 2 enzymes had half-lives (t 1 2) of 82 and 34 days, respectively. In the patients, HGPRTase was absent even in the youngest circulating erythrocytes, and the half-life of APRTase was prolonged to 86 days. Extrapolation of the observed data indicates that at day zero, the specific activity of the APRTase was the same in erythrocytes of both groups but was about 3 times as great in patient cells at 120 days. The heat stability of both enzymes from cells of various ages did not differ between the 2 groups of children. These data suggest that the increase in AMP pyrophosphorylase in patients is due to altered enzyme stability, not to inherent differences in concentration.