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Concentration of phosphoribosyl pyrophosphate in the kidney during development and in experimental diabetic
Insights
Kidney phosphoribosyl pyrophosphate (PPRibP) levels increase with age in rats as kidney growth slows. Diabetes causes a temporary fall in PPRibP, which recovers as kidney hypertrophy lessens.
Area of Science:
- Biochemistry
- Developmental Biology
- Nephrology
Background:
- Phosphoribosyl pyrophosphate (PPRibP) is a crucial intermediate in nucleotide biosynthesis.
- Understanding PPRibP dynamics is vital for comprehending kidney metabolic adaptations during growth and disease.
Purpose of the Study:
- To investigate the developmental changes in rat kidney PPRibP content from fetal stages to 100 days.
- To examine the impact of short-term diabetes on renal PPRibP levels in immature and adult rats.
Main Methods:
- Quantification of kidney PPRibP content across different developmental ages in rats.
- Induction of diabetes in rats to assess changes in renal PPRibP and kidney hypertrophy.
- Measurement of phosphoribosyl pyrophosphate synthetase activity.
Main Results:
- Renal PPRibP content is lowest in young rats and increases as kidney growth decelerates.
- In adult rats, diabetes-induced kidney hypertrophy is associated with a decrease in PPRibP, which normalizes as hypertrophy subsides.
- Diabetes in immature rats leads to less pronounced kidney hypertrophy and a smaller reduction in renal PPRibP.
Conclusions:
- Kidney PPRibP levels are inversely related to the rate of kidney growth during development.
- Diabetes transiently alters renal PPRibP metabolism, with changes correlating to the extent of kidney hypertrophy.
- PPRibP synthetase activity remains stable, suggesting regulatory mechanisms involve PPRibP utilization rather than synthesis.
Abstract:
The effect of developmental growth on the kidney content of phosphoribosyl pyrophosphate PPRibP was studied in rats at ages between the foetal animal and up to 100 days of age. In addition, the effect of short-term diabetes (up to 14 days) on the renal content of PPRibP was studied in immature rats and in adults aged approx. 60 days. The developmental pattern of PPRibP is such that the PPRibP content is lowest in the young rat and increases as the rate of kidney growth slows. In the adult rat, the early kidney hypertrophy of diabetes is accompanied by a fall in PPRibP content and, again, the PPRibP content returns to normal as the rate of kidney hypertrophy diminishes. Induction of diabetes in the immature rat causes a lesser degree of kidney hypertrophy and also a smaller depression of renal PPRibP content. The activity of PPRibP synthetase (EC 2.7.6.1) is not significantly affected by age or diabetes. The changes in PPRibP content are discussed in relation to the generation of ribose 5-phosphate by the pentose phosphate pathway and the utilization of PPRibP for nucleotide synthesis via the 'de novo' and salvage pathways.