TY - JOUR
T1 - Metabolic channeling
T2 - predictions, deductions, and evidence
AU - Pareek, Vidhi
AU - Sha, Zhou
AU - He, Jingxuan
AU - Wingreen, Ned S.
AU - Benkovic, Stephen J.
N1 - Funding Information:
S.J.B. acknowledges support by NIH grant GM024129-40 . V.P. thanks the Huck Institutes of Life Sciences, Penn State for financial support. N.S.W. acknowledges support in part by the National Science Foundation , through the Center for the Physics of Biological Function ( PHY-1734030 ), and NIH grant R01GM140032 .
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9/16
Y1 - 2021/9/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2021.08.030
DO - 10.1016/j.molcel.2021.08.030
M3 - Review article
C2 - 34547238
AN - SCOPUS:85115272652
VL - 81
SP - 3775
EP - 3785
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 18
ER -