Metabolic channeling: predictions, deductions, and evidence.


Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
16 09 2021
Historique:
received: 27 05 2021
revised: 18 08 2021
accepted: 21 08 2021
entrez: 21 9 2021
pubmed: 22 9 2021
medline: 16 10 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34547238
pii: S1097-2765(21)00697-3
doi: 10.1016/j.molcel.2021.08.030
pmc: PMC8485759
mid: NIHMS1736245
pii:
doi:

Substances chimiques

Multienzyme Complexes 0
Purines 0
purine W60KTZ3IZY

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

3775-3785

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM024129
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM082938
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM140032
Pays : United States
Organisme : NIGMS NIH HHS
ID : R37 GM024129
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Références

Biomolecules. 2018 Dec 03;8(4):
pubmed: 30513998
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1368-73
pubmed: 25605889
Biochemistry. 1999 Jun 22;38(25):7891-9
pubmed: 10387030
PLoS Comput Biol. 2014 Feb 20;10(2):e1003483
pubmed: 24586134
Curr Opin Chem Biol. 2019 Feb;48:44-54
pubmed: 30458335
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13009-13014
pubmed: 30509995
Biochemistry. 1996 Apr 2;35(13):4211-21
pubmed: 8672457
Trends Pharmacol Sci. 2021 Oct;42(10):845-856
pubmed: 34373114
ACS Chem Biol. 2016 Jul 15;11(7):1917-24
pubmed: 27128383
Biochemistry. 1997 Jun 24;36(25):7664-80
pubmed: 9201907
Crit Rev Biochem Mol Biol. 2021 Feb;56(1):1-16
pubmed: 33179964
Elife. 2016 Jun 09;5:
pubmed: 27278775
Mol Syst Biol. 2011 Nov 08;7:548
pubmed: 22068331
Biochemistry. 1985 Sep 24;24(20):5343-50
pubmed: 3907701
Phytochem Rev. 2018;17(2):211-227
pubmed: 29755303
Biochim Biophys Acta. 1996 Mar 15;1289(2):175-86
pubmed: 8600971
J Biol Chem. 1985 Dec 5;260(28):15008-12
pubmed: 4066662
J Phys Chem B. 2021 Mar 4;125(8):2061-2073
pubmed: 33596074
Biophys J. 2017 Feb 28;112(4):767-779
pubmed: 28256236
Biochemistry. 2005 Sep 13;44(36):11974-85
pubmed: 16142895
Chembiochem. 2008 May 5;9(7):1024-8
pubmed: 18351684
Mol Syst Biol. 2020 Mar;16(3):e9232
pubmed: 32133759
Nat Commun. 2018 May 30;9(1):2136
pubmed: 29849027
Trends Cell Biol. 2020 Jan;30(1):4-14
pubmed: 31753533
Mol Biosyst. 2015 Jan;11(1):38-59
pubmed: 25360565
Phys Rev Lett. 2013 May 17;110(20):208104
pubmed: 25167456
Nat Prod Rep. 2007 Oct;24(5):1041-72
pubmed: 17898897
Biochemistry. 1996 Oct 1;35(39):12652-8
pubmed: 8841108
J Chem Phys. 2014 Mar 14;140(10):105101
pubmed: 24628210
Proc Natl Acad Sci U S A. 1982 May;79(10):3236-40
pubmed: 6954476
Adv Enzymol Relat Areas Mol Biol. 1998;72:87-144
pubmed: 9559052
Annu Rev Biochem. 1987;56:89-124
pubmed: 2441660
BMC Genomics. 2010 Feb 10;11 Suppl 1:S3
pubmed: 20158874
Nat Commun. 2018 Sep 3;9(1):3570
pubmed: 30177711
PLoS One. 2017 Feb 24;12(2):e0172673
pubmed: 28234973
Plant Commun. 2020 Jun 05;2(1):100081
pubmed: 33511342
FASEB J. 1990 Nov;4(14):3224-33
pubmed: 2227213
Arch Biochem Biophys. 1977 Jan 30;178(2):652-61
pubmed: 189701
J Mol Biol. 2013 Nov 15;425(22):4323-33
pubmed: 23816837
Annu Rev Biochem. 2000;69:961-1004
pubmed: 10966480
Nat Chem Biol. 2018 Dec;14(12):1127-1132
pubmed: 30374166
Nat Chem. 2016 Apr;8(4):299-309
pubmed: 27001725
Emerg Top Life Sci. 2020 Dec 11;4(3):247-261
pubmed: 33048111
Biochemistry. 1986 Jul 29;25(15):4240-9
pubmed: 3530321
Arch Biochem Biophys. 1977 Dec;184(2):529-34
pubmed: 563705
Phys Chem Chem Phys. 2017 Jun 14;19(23):15463-15470
pubmed: 28580995
J R Soc Interface. 2019 Jul 26;16(156):20190444
pubmed: 31362617
Curr Opin Struct Biol. 2016 Dec;41:10-18
pubmed: 27266330
Biochemistry. 2007 Nov 13;46(45):13223-34
pubmed: 17927213
J Biol Chem. 1995 Dec 15;270(50):29936-44
pubmed: 8530393
Chem Commun (Camb). 2015 Jan 25;51(7):1244-7
pubmed: 25471208
Biochemistry. 2017 Jun 27;56(25):3184-3196
pubmed: 28580779
Sci Rep. 2019 Jan 24;9(1):455
pubmed: 30679600
Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):E5354-62
pubmed: 27551079
Mol Biosyst. 2014 Mar 4;10(3):369-74
pubmed: 24413256
Annu Rev Biophys Biophys Chem. 1986;15:97-117
pubmed: 3013232
Science. 2007 Apr 13;316(5822):254-61
pubmed: 17431175
Nat Metab. 2021 Jan;3(1):90-106
pubmed: 33398195
J Biol Chem. 2002 Mar 22;277(12):10653-60
pubmed: 11756454
Biochem Soc Trans. 1993 Feb;21(1):181-6
pubmed: 8383607
Trends Biochem Sci. 2017 Feb;42(2):141-154
pubmed: 28029518
J Cell Sci. 2019 Nov 21;132(22):
pubmed: 31754043
Protein Sci. 2018 Feb;27(2):463-471
pubmed: 29094409
Biochemistry. 1969 Jul;8(7):2787-94
pubmed: 4309123
Nat Nanotechnol. 2014 Jul;9(7):531-6
pubmed: 24859813
J Theor Biol. 1991 Sep 7;152(1):57-61
pubmed: 1753768
J Biol Chem. 1988 Nov 25;263(33):17857-71
pubmed: 3053720
Sci Rep. 2020 Jun 25;10(1):10349
pubmed: 32587383
Proc Natl Acad Sci U S A. 1973 Sep;70(9):2534-8
pubmed: 4354855
Biochemistry. 2014 May 13;53(18):2875-83
pubmed: 24779441
Nat Struct Biol. 1996 Jan;3(1):74-86
pubmed: 8548458
Acc Chem Res. 2003 Jul;36(7):539-48
pubmed: 12859215
Plant Physiol. 2020 Apr;182(4):1883-1893
pubmed: 32041908
J Mol Biol. 2018 Dec 7;430(24):5066-5079
pubmed: 30367843
Trends Biochem Sci. 1994 May;19(5):193-7
pubmed: 8048159
Nat Rev Mol Cell Biol. 2021 Mar;22(3):215-235
pubmed: 33169001
Biochemistry. 1994 Oct 4;33(39):11692-8
pubmed: 7918385
J Biol Chem. 2020 Jul 10;295(28):9551-9566
pubmed: 32439803
J Phys Chem Lett. 2010 May 6;1(9):1332-1335
pubmed: 20454551
J Biol Chem. 1991 Nov 15;266(32):21548-57
pubmed: 1939184
Nat Biotechnol. 2014 Oct;32(10):1011-8
pubmed: 25262299
Biochemistry. 1980 Sep 2;19(18):4313-21
pubmed: 7417406
Science. 2016 Nov 18;354(6314):890-893
pubmed: 27856908
Biochemistry. 2013 Aug 6;52(31):5225-35
pubmed: 23841499
Curr Opin Cell Biol. 2020 Oct;66:28-33
pubmed: 32417394
Curr Microbiol. 2000 Apr;40(4):245-9
pubmed: 10688693
Science. 2020 Apr 17;368(6488):283-290
pubmed: 32299949
Adv Enzymol Relat Areas Mol Biol. 1973;39:91-183
pubmed: 4355768
Int J Mol Sci. 2008 May;9(5):751-67
pubmed: 19325782
Biochemistry. 1994 Mar 1;33(8):2269-78
pubmed: 8117684
J Biol Chem. 1991 May 5;266(13):8020-33
pubmed: 1902468
Biochemistry. 2011 Apr 26;50(16):3346-56
pubmed: 21413787
Chem Rec. 2001;1(2):140-51
pubmed: 11893063
Mol Biol Cell. 2013 Sep;24(17):2593-6
pubmed: 23989722
Biochemistry. 2007 Feb 27;46(8):2156-73
pubmed: 17261030
Nat Chem Biol. 2020 Sep;16(9):973-978
pubmed: 32632294
ACS Chem Biol. 2016 Oct 21;11(10):2847-2853
pubmed: 27556423
Essays Biochem. 2018 Oct 26;62(4):501-514
pubmed: 30315098
J Cell Biol. 1981 Dec;91(3 Pt 2):227s-255s
pubmed: 7033239
Annu Rev Biochem. 2001;70:149-80
pubmed: 11395405
Eur J Biochem. 1980 Dec;112(3):431-42
pubmed: 7007046
J Biol Chem. 2002 Apr 5;277(14):12137-43
pubmed: 11821399
Biochem J. 1989 Dec 1;264(2):605-7
pubmed: 2604733
Q Rev Biophys. 1999 Feb;32(1):1-56
pubmed: 10800520
J Mol Biol. 2010 Jan 15;395(2):417-29
pubmed: 19900465
Cell. 2007 Apr 20;129(2):319-32
pubmed: 17448991
Int J Mol Sci. 2021 Jul 01;22(13):
pubmed: 34281155
J Proteome Res. 2019 May 3;18(5):2078-2087
pubmed: 30964683
Cell Biosci. 2021 Jan 29;11(1):27
pubmed: 33514425

Auteurs

Vidhi Pareek (V)

Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.

Zhou Sha (Z)

Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.

Jingxuan He (J)

Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.

Ned S Wingreen (NS)

Department of Molecular Biology and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.

Stephen J Benkovic (SJ)

Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA. Electronic address: sjb1@psu.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH