Near-equilibrium glycolysis supports metabolic homeostasis and energy yield

Park, Junyoung O.; Tanner, Lukas B.; Wei, Monica H.; Khana, Daven B.; Jacobson, Tyler B.; Zhang, Zheyun; Rubin, Sara A.; Li, Sophia Hsin-Jung; Higgins, Meytal B.; Stevenson, David M.; Amador-Noguez, Daniel; Rabinowitz, Joshua D.

doi:10.1038/s41589-019-0364-9

Title: Near-equilibrium glycolysis supports metabolic homeostasis and energy yield

Journal Article · 23 September 2019 · Nature Chemical Biology

DOI: https://doi.org/10.1038/s41589-019-0364-9 · OSTI ID:1570470

^[1]; Tanner, Lukas B. ^[2]; Wei, Monica H. ^[2];

^[3]; Jacobson, Tyler B. ^[3]; Zhang, Zheyun ^[2];

^[2]; Li, Sophia Hsin-Jung ^[2]; Higgins, Meytal B. ^[4]; Stevenson, David M. ^[3];

^[3];

^[2]

Univ. of California, Los Angeles, CA (United States); Princeton Univ., NJ (United States); CABBI
Princeton Univ., NJ (United States)
Univ. of Wisconsin, Madison, WI (United States)
Princeton Univ., NJ (United States); ExxonMobil Research and Engineering Company, Annandale, NJ (United States)

Glycolysis plays a central role in producing ATP and biomass. Its control principles, however, remain incompletely understood. In this work, we create a method that combines ²H and ¹³C tracers to determine glycolytic thermodynamics. With this method, we show that, in conditions and organisms with relatively slow fluxes, multiple steps in glycolysis are near to equilibrium, reflecting spare enzyme capacity. In Escherichia coli, nitrogen or phosphorus upshift rapidly increases the thermodynamic driving force, deploying the spare enzyme capacity to increase flux. Similarly, respiration inhibition in mammalian cells rapidly increases both glycolytic flux and the thermodynamic driving force. The thermodynamic shift allows flux to increase with only small metabolite concentration changes. Finally, we find that the cellulose-degrading anaerobe Clostridium cellulolyticum exhibits slow, near-equilibrium glycolysis due to the use of pyrophosphate rather than ATP for fructose-bisphosphate production, resulting in enhanced per-glucose ATP yield. Thus, near-equilibrium steps of glycolysis promote both rapid flux adaptation and energy efficiency.

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Research Organization:: Univ. of Illinois, Champaign, IL (United States); Princeton Univ., NJ (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: SC0018420; SC0012461; AC05-00OR22725

OSTI ID:: 1570470

Journal Information:: Nature Chemical Biology, Journal Name: Nature Chemical Biology Journal Issue: 10 Vol. 15; ISSN 1552-4450

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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