Metabolic channeling: predictions, deductions, and evidence

Vidhi Pareek, Zhou Sha, Jingxuan He, Ned S. Wingreen, Stephen J. Benkovic

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3775-3785
Number of pages11
JournalMolecular Cell
Volume81
Issue number18
DOIs
StatePublished - Sep 16 2021

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • membrane-less compartmentalization
  • metabolic channeling
  • metabolon
  • molecular tunnel
  • purinosome

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