Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase. (28th May 2018)

• Record Type: Journal Article
• Authors: Camici, Marcella; Allegrini, Simone; Tozzi, Maria Grazia
• Is Part Of: FEBS journal. Volume 285:Number 18(2018)
• Page Start: 3337
• Page End: 3352
• Publication Date: 2018-05-28
• Subjects: adenine -- adenosine -- AICAR -- AMP -- AMP‐dependent protein kinase -- purine de novo synthesis -- purine salvage synthesis; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14508
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps. The salvage pathways utilize hypoxanthine, guanine and adenine to generate the corresponding mononucleotides. Despite several decades of research on the subject, new and surprising findings on purine metabolism are constantly being reported, and some aspects still need to be elucidated. Recently, purine biosynthesis has been linked to the metabolic pathways regulated by AMP‐activated protein kinase (AMPK). AMPK is the master regulator of cellular energy homeostasis, and its activity depends on the AMP : ATP ratio. The cellular energy status and AMPK activation are connected by AMP, an allosteric activator of AMPK. Hence, an indirect strategy to affect AMPK activity would be to target the pathways that generate AMP in the cell. Herein, we report an up‐to‐date review of the interplay between AMPK and adenylate metabolizing enzymes. Some aspects of inborn errors of purine metabolism are also discussed. Abstract : The complex array interconnecting adenylate metabolizing enzymes and AMP‐activated protein kinase (AMPK). In the upper part of the figure, the enzyme activities regulating AMP homeostasis are shown. These belong both to de novo and salvage pathways of purine compounds. In the lower part of the figure, a selection of metabolic pathways regulated by AMPK activation is shown.