Title | Metabolic channeling: predictions, deductions, and evidence. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Pareek, V, Sha, Z, He, J, Wingreen, NS, Benkovic, SJ |
Journal | Mol Cell |
Volume | 81 |
Issue | 18 |
Pagination | 3775-3785 |
Date Published | 2021 09 16 |
ISSN | 1097-4164 |
Keywords | Animals, 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> |
DOI | 10.1016/j.molcel.2021.08.030 |
Alternate Journal | Mol Cell |
PubMed ID | 34547238 |
PubMed Central ID | PMC8485759 |
Grant List | R01 GM024129 / GM / NIGMS NIH HHS / United States R01 GM140032 / GM / NIGMS NIH HHS / United States R37 GM024129 / GM / NIGMS NIH HHS / United States |