Reaction Energetics and13 C Fractionation of Alanine Transamination in the Aqueous and Gas Phases

McNeill, Ashley S.; Dallas, Brooke H.; Eiler, John M.; Bylaska, Eric J.; Dixon, David A.

doi:10.1021/acs.jpca.9b11783

Title: Reaction Energetics and¹³ C Fractionation of Alanine Transamination in the Aqueous and Gas Phases

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Abstract

The alanine transaminase enzyme catalyzes the transfer of an amino group from alanine to α-ketoglutarate to produce pyruvate and glutamate. Isotope fractionation factors (IFFs) for the reaction +H₃NCH(CH₃)COO^– + ^–OOCCH₂CH₂C(O)COO^– ↔ CH₃C(O)COO^– + ⁺H₃NCH(CH₂CH₂COO^–)COO^– (zwitterionic neutral alanine + doubly deprotonated α-ketoglutarate ↔ pyruvate + zwitterionic glutamate anion) were calculated from the partition functions of explicitly and implicitly solvated molecules at 298 K. Calculations were done for alanine (noncharge separated, zwitterion, deprotonated), pyruvic acid (neutral, deprotonated), glutamic acid (noncharge separated, zwitterion, deprotonated, doubly deprotonated), and α-ketoglutaric acid (neutral, deprotonated, doubly deprotonated). The computational results, calculated from gas phase- and aqueous-optimized clusters with explicit H₂O molecules at the MP2/aug-cc-pVDZ and MP2/aug-cc-pVDZ/COSMO levels, respectively, predict that substitution of ¹³C at the C2 position of alanine and pyruvic acid and their various forms leads to the C2 position of pyruvic acid/pyruvate being enriched in ¹³C/¹²C ratio by 9‰. Simpler approaches that estimate the IFFs based solely on changes in the zero-point energies (ZPEs) are consistent with the higher-level model. ZPE-based IFFs calculated for simple analogues formaldehyde and methylamine (analogous to the C2 positions of pyruvate and alanine, respectively) predict a ¹³C enrichment in formaldehyde of 7–8‰ at the MP2/aug-cc-pVDZ and aug-cc-pVTZ levels. A simplemore »« less

Authors:

McNeill, Ashley S. ^[1]; Dallas, Brooke H. ^[2]; Eiler, John M. ^[2];

^[3];

^[1]

Univ. of Alabama, Tuscaloosa, AL (United States)
California Institute of Technology (CalTech), Pasadena, CA (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)

Publication Date:: Thu Jan 30 00:00:00 EST 2020

Research Org.:: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:: 1607674

Report Number(s):: PNNL-SA-150162
Journal ID: ISSN 1089-5639

Grant/Contract Number:: AC05-76RL01830

Resource Type:: Accepted Manuscript

Journal Name:: Journal of Physical Chemistry. A, Molecules, Spectroscopy, Kinetics, Environment, and General Theory

Additional Journal Information:: Journal Volume: 124; Journal Issue: 10; Journal ID: ISSN 1089-5639

Publisher:: American Chemical Society

Country of Publication:: United States

Language:: English

Subject:: 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Deprotonation; Chemical reactions; Peptides and proteins; Monomers; Molecules

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                    McNeill, Ashley S., Dallas, Brooke H., Eiler, John M., Bylaska, Eric J., and Dixon, David A. Reaction Energetics and13 C Fractionation of Alanine Transamination in the Aqueous and Gas Phases.  United States: N. p., 2020. 
Web.  doi:10.1021/acs.jpca.9b11783.

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                    McNeill, Ashley S., Dallas, Brooke H., Eiler, John M., Bylaska, Eric J., & Dixon, David A. Reaction Energetics and13 C Fractionation of Alanine Transamination in the Aqueous and Gas Phases.  United States.  https://doi.org/10.1021/acs.jpca.9b11783

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                    McNeill, Ashley S., Dallas, Brooke H., Eiler, John M., Bylaska, Eric J., and Dixon, David A. Thu .  
"Reaction Energetics and13 C Fractionation of Alanine Transamination in the Aqueous and Gas Phases".  United States.  https://doi.org/10.1021/acs.jpca.9b11783.  https://www.osti.gov/servlets/purl/1607674.

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@article{osti_1607674,

  title        = {Reaction Energetics and13 C Fractionation of Alanine Transamination in the Aqueous and Gas Phases},

  author       = {McNeill, Ashley S. and Dallas, Brooke H. and Eiler, John M. and Bylaska, Eric J. and Dixon, David A.},

  abstractNote = {The alanine transaminase enzyme catalyzes the transfer of an amino group from alanine to α-ketoglutarate to produce pyruvate and glutamate. Isotope fractionation factors (IFFs) for the reaction +H3NCH(CH3)COO– + –OOCCH2CH2C(O)COO– ↔ CH3C(O)COO– + +H3NCH(CH2CH2COO–)COO– (zwitterionic neutral alanine + doubly deprotonated α-ketoglutarate ↔ pyruvate + zwitterionic glutamate anion) were calculated from the partition functions of explicitly and implicitly solvated molecules at 298 K. Calculations were done for alanine (noncharge separated, zwitterion, deprotonated), pyruvic acid (neutral, deprotonated), glutamic acid (noncharge separated, zwitterion, deprotonated, doubly deprotonated), and α-ketoglutaric acid (neutral, deprotonated, doubly deprotonated). The computational results, calculated from gas phase- and aqueous-optimized clusters with explicit H2O molecules at the MP2/aug-cc-pVDZ and MP2/aug-cc-pVDZ/COSMO levels, respectively, predict that substitution of 13C at the C2 position of alanine and pyruvic acid and their various forms leads to the C2 position of pyruvic acid/pyruvate being enriched in 13C/12C ratio by 9‰. Simpler approaches that estimate the IFFs based solely on changes in the zero-point energies (ZPEs) are consistent with the higher-level model. ZPE-based IFFs calculated for simple analogues formaldehyde and methylamine (analogous to the C2 positions of pyruvate and alanine, respectively) predict a 13C enrichment in formaldehyde of 7–8‰ at the MP2/aug-cc-pVDZ and aug-cc-pVTZ levels. A simple predictive model using canonical functional group frequencies and reduced masses for 13C exchange between R2C=O and R2CH–NH2 predicted enrichment in R2C=O that is too large by a factor of two but is qualitatively accurate compared with the more sophisticated models. Our models are all in agreement with the expectation that pyruvate and formaldehyde will be preferentially enriched in 13C because of the strength of their >C=O bond relative to that of ≡C–NH2 in alanine and methylamine. 13C/12C substitution is also modeled at the methyl and carboxylic acid sites of alanine and pyruvic acid, respectively.},

  doi          = {10.1021/acs.jpca.9b11783},

  journal      = {Journal of Physical Chemistry. A, Molecules, Spectroscopy, Kinetics, Environment, and General Theory},

  number       = 10,

  volume       = 124,

  place        = {United States},

  year         = {Thu Jan 30 00:00:00 EST 2020},

  month        = {Thu Jan 30 00:00:00 EST 2020}

}

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Title: Reaction Energetics and13 C Fractionation of Alanine Transamination in the Aqueous and Gas Phases

Abstract

Citation Formats

Title: Reaction Energetics and¹³ C Fractionation of Alanine Transamination in the Aqueous and Gas Phases