Aspects of the regulation of hepatic phosphoribosyl pyrophosphate formation in the obese (ob/ob) mouse: relationship to the pentose phosphate pathway.

The content of phosphoribosyl pyrophosphate (PPRibP) and of intermediates involved in its synthesis has been measured in the livers of obese (ob/ob) mice 2 months and 3-4 months of age, a period of dynamic growth and marked hepatic hypertrophy and hyperplasia, and comparison made with the values found in the lean age-matched control groups. The total hepatic PPRibP content and PPRibP/mg DNA was significantly increased in the 3- to 4-month-old obese mice relative to both the lean control groups and the 2-month-old obese mice, illustrating the significant changes occurring in the obese mouse liver in this transition period. The change in hepatic PPRibP/mg DNA in the obese mice is positively correlated with age (up to 4 months, body weight 60 g) and with parameters linked to the activity of the pentose phosphate pathway. There is no apparent correlation between PPRibP concentration and inorganic phosphate, the energy status of the cell, or the hepatic PPRibP synthetase (EC 2.7.6.1.) activity. The increase in the bioavailability of PPRibP, which is both a substrate and activator of the de novo and salvage pathways of purine and pyrimidine synthesis, is considered in relation to the increased nucleotide requirement associated with the rise in total hepatic RNA, DNA, and adenine nucleotide in the obese mouse.