Metabolic channeling: predictions, deductions, and evidence.

TitleMetabolic channeling: predictions, deductions, and evidence.
Publication TypeJournal Article
Year of Publication2021
AuthorsPareek, V, Sha, Z, He, J, Wingreen, NS, Benkovic, SJ
JournalMol Cell
Volume81
Issue18
Pagination3775-3785
Date Published2021 09 16
ISSN1097-4164
KeywordsAnimals, Humans, Metabolic Networks and Pathways, Metabolism, Metabolome, Multienzyme Complexes, Protein Interaction Maps, Purines
Abstract

<p>With the elucidation of myriad anabolic and catabolic enzyme-catalyzed cellular pathways crisscrossing each other, an obvious question arose: how could these networks operate with maximal catalytic efficiency and minimal interference? A logical answer was the postulate of metabolic channeling, which in its simplest embodiment assumes that the product generated by one enzyme passes directly to a second without diffusion into the surrounding medium. This tight coupling of activities might increase a pathway's metabolic flux and/or serve to sequester unstable/toxic/reactive intermediates as well as prevent their access to other networks. Here, we present evidence for this concept, commencing with enzymes that feature a physical molecular tunnel, to multi-enzyme complexes that retain pathway substrates through electrostatics or enclosures, and finally to metabolons that feature collections of enzymes assembled into clusters with variable stoichiometric composition. Lastly, we discuss the advantages of reversibly assembled metabolons in the context of the purinosome, the purine biosynthesis metabolon.</p>

DOI10.1016/j.molcel.2021.08.030
Alternate JournalMol Cell
PubMed ID34547238
PubMed Central IDPMC8485759
Grant ListR01 GM024129 / GM / NIGMS NIH HHS / United States
R01 GM140032 / GM / NIGMS NIH HHS / United States
R37 GM024129 / GM / NIGMS NIH HHS / United States