Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism

Christopher T. Walsh, Benjamin P. Tu, Yi Tang

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

Contemporary analyses of cell metabolism have called out three metabolites: ATP, NADH, and acetyl-CoA, as sentinel molecules whose accumulation represent much of the purpose of the catabolic arms of metabolism and then drive many anabolic pathways. Such analyses largely leave out how and why ATP, NADH, and acetyl-CoA (Figure 1) at the molecular level play such central roles. Yet, without those insights into why cells accumulate them and how the enabling properties of these key metabolites power much of cell metabolism, the underlying molecular logic remains mysterious. Four other metabolites, S-adenosylmethionine, carbamoyl phosphate, UDP-glucose, and Δ2-isopentenyl-PP play similar roles in using group transfer chemistry to drive otherwise unfavorable biosynthetic equilibria. This review provides the underlying chemical logic to remind how these seven key molecules function as mobile packets of cellular currencies for phosphoryl transfers (ATP), acyl transfers (acetyl-CoA, carbamoyl-P), methyl transfers (SAM), prenyl transfers (IPP), glucosyl transfers (UDP-glucose), and electron and ADP-ribosyl transfers (NAD(P)H/NAD(P)+) to drive metabolic transformations in and across most primary pathways. The eighth key metabolite is molecular oxygen (O2), thermodynamically activated for reduction by one electron path, leaving it kinetically stable to the vast majority of organic cellular metabolites.

Original languageEnglish (US)
Pages (from-to)1460-1494
Number of pages35
JournalChemical Reviews
Volume118
Issue number4
DOIs
StatePublished - Feb 28 2018

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Metabolites
Metabolism
NAD
Acetyl Coenzyme A
Molecules
Uridine Diphosphate Glucose
Adenosine Triphosphate
Carbamyl Phosphate
S-Adenosylmethionine
Electrons
Molecular oxygen
Adenosine Diphosphate

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism. / Walsh, Christopher T.; Tu, Benjamin P.; Tang, Yi.

In: Chemical Reviews, Vol. 118, No. 4, 28.02.2018, p. 1460-1494.

Research output: Contribution to journalReview article

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