Purine biosynthesis is the enzymatic formation of purine nucleotides through sequential construction of the purine ring on an activated ribose framework. The de novo pathway uses phosphoribosyl pyrophosphate together with amino-acid-derived atoms, carbon dioxide, and folate-associated one-carbon units to produce inosine monophosphate [1]. Physical association among pathway enzymes can facilitate transfer of intermediates between successive reactions [2]. In mammalian cells, dynamic assemblies called purinosomes organize enzymes of this pathway and associate with cellular sources of required metabolites [3]. Inosine monophosphate branches toward adenine and guanine nucleotides, with additional reactions establishing their phosphorylation states. Feedback inhibition, enzyme expression, and precursor supply coordinate purine production with cellular demand [4].
- purine nucleotides
- inosine monophosphate
- PRPP
- one-carbon metabolism
References
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- Vidhi Pareek; Zhou Sha; Jingxuan He; Ned S. Wingreen; Stephen J. Benkovic; Metabolic Channeling: Predictions, Deductions, and Evidence. Mol. Cell 2021, 81, 3775-3785, 10.1016/j.molcel.2021.08.030.
- Anthony M. Pedley; Vidhi Pareek; Stephen J. Benkovic; The Purinosome: A Case Study for a Mammalian Metabolon. Annu. Rev. Biochem. 2022, 91, 89-106, 10.1146/annurev-biochem-032620-105728.
- Andrew N Lane; Teresa W-M Fan; Regulation of Mammalian Nucleotide Metabolism and Biosynthesis. Nucleic Acids Res. 2015, 43, 2466-2485, 10.1093/nar/gkv047.