Metabolic channeling: predictions, deductions, and evidence

Citation:

Pareek, V., et al. “Metabolic channeling: predictions, deductions, and evidence”. Mol Cell 81 (2021): , 81, 3775-3785. Print.

Number:

18

Date Published:

Sep 16

ISBN Number:

1097-2765 (Print)1097-2765

Accession Number:

34547238

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.

Notes:

1097-4164Pareek, VidhiSha, ZhouHe, JingxuanWingreen, Ned SBenkovic, Stephen JR01 GM024129/GM/NIGMS NIH HHS/United StatesR01 GM140032/GM/NIGMS NIH HHS/United StatesR37 GM024129/GM/NIGMS NIH HHS/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Review2021/09/22Mol Cell. 2021 Sep 16;81(18):3775-3785. doi: 10.1016/j.molcel.2021.08.030.

Last updated on 02/16/2022