Purine and pyrimidine metabolism: pathways, pitfalls and perturbations.
The conceptual framework which underlies many studies of purine and pyrimidine metabolism in intact cells has been critically evaluated. The model that is implicit in many such studies is the single, partially purified enzyme. This paper gives examples both of instances in which the extrapolation of results of enzymes studies to intact cells has been successful and of instances in which enzymes behave differently in the intact cell than in cell extracts. Pitfalls in the extrapolation of results of enzyme studies to intact cells concern (a) metabolic pathways, (b) intracellular enzyme activities, (c) enzyme regulation, and (d) intracellular metabolite concentrations. Examples are also given of situations in which perturbations in one aspect of purine or pyrimidine metabolism lead to changes in other aspects, often distant in the network of reactions.
D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000818:Animals; D008223:Lymphoma / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism; D010754:Phosphoribosyl Pyrophosphate / Q000096:biosynthesis; D011685:Purine Nucleotides / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism*; D012268:Ribose-Phosphate Pyrophosphokinase / Q000378:metabolism
D009711:Nucleotides; D011685:Purine Nucleotides; D011687:Purines; D011742:Pyrimidine Nucleotides; D011743:Pyrimidines; D010754:Phosphoribosyl Pyrophosphate; D000228:Adenine Phosphoribosyltransferase; D012268:Ribose-Phosphate Pyrophosphokinase; D009173:Mycophenolic Acid; D008727:Methotrexate