Abstract
Detecting the molecular targets of xenobiotic substances in vivo poses a considerable analytical challenge. Here, we describe the use of an NMR-based tracer methodology for the instantaneous in vivo observation of sulfur(IV) action on cellular metabolism. Specifically, we find that glycolytic flux is directed towards sulfite adducts of dihydroxyacetone phosphate and pyruvate as off-pathway intermediates that obstruct glycolytic flux. In particular, the pyruvatesulfite association hinders the formation of downstream metabolites. The apparent in vivo association constant of pyruvate and sulfite agrees with the apparent inhibition constant of CO2 formation, thus supporting the importance of pyruvate interception in disturbing central metabolism and inhibiting NAD regeneration.
| Original language | English |
|---|---|
| Journal | ChemBioChem |
| Volume | 13 |
| Issue number | 15 |
| Pages (from-to) | 2265-2269 |
| Number of pages | 5 |
| ISSN | 1439-4227 |
| DOIs | |
| Publication status | Published - 2012 |
| Externally published | Yes |
Keywords
- Glycolysis
- Magnetic Resonance Spectroscopy
- Pyruvic Acid
- Saccharomyces cerevisiae
- Sulfites
- Xenobiotics
- 8558G7RUTR Pyruvic Acid
- carbon dioxide
- dihydroxyacetone phosphate
- glyceraldehyde 3 phosphate dehydrogenase
- pyruvic acid
- sulfite
- article
- binding affinity
- carbon metabolism
- carbon nuclear magnetic resonance
- cell metabolism
- complex formation
- dissociation constant
- enzyme inhibition
- glycolysis
- in vivo study
- nonhuman
- priority journal
- DNP
- In vivo NMR spectroscopy
- Kinetics
- Metabolism
- cellular metabolism
- glycolytic flux
- Fungi Plantae (Fungi, Microorganisms, Nonvascular Plants, Plants) - Ascomycetes [15100] Saccharomyces cerevisiae species yeast common strain-BY4742
- carbon dioxide 124-38-9
- dihydroxyacetone phosphate-sulfite adduct
- intermediates
- NAD 53-84-9 inhibition
- pyruvate-sulfite adduct
- sulfur(IV) 20681-10-1
- 02502, Cytology - General
- 02504, Cytology - Plant
- 10060, Biochemistry studies - General
- 10062, Biochemistry studies - Nucleic acids, purines and pyrimidines
- 13002, Metabolism - General metabolism and metabolic pathways
- 51519, Plant physiology - Metabolism
- 51522, Plant physiology - Chemical constituents
- in vivo real-time hyperpolarized carbon-13 NMR spectroscopy laboratory techniques, spectrum analysis techniques
- Biochemistry and Molecular Biophysics
- Cell Biology
- Methods and Techniques
- BIOCHEMISTRY
- CHEMISTRY,
- SACCHAROMYCES-CEREVISIAE
- ENERGY-METABOLISM
- ATP CONTENT
- YEAST
- OXIDASE
- ASTHMA
- INCUBATION
- TOXICITY
- NITRITE
- in vivo NMR spectroscopy
- kinetics
- metabolism
- sulfites