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RSS FeedsIJMS, Vol. 23, Pages 8766: Myoglobin–Pyruvate Interactions: Binding Thermodynamics, Structure–Function Relationships, and Impact on Oxygen Release Kinetics (International Journal of Molecular Sciences)

 
 

6 august 2022 15:00:38

 
IJMS, Vol. 23, Pages 8766: Myoglobin–Pyruvate Interactions: Binding Thermodynamics, Structure–Function Relationships, and Impact on Oxygen Release Kinetics (International Journal of Molecular Sciences)
 


Myoglobin (Mb), besides its roles as an oxygen (O2) carrier/storage protein and nitric oxide NO scavenger/producer, may participate in lipid trafficking and metabolite binding. Our recent findings have shown that O2 is released from oxy-Mb upon interaction with lactate (LAC, anerobic glycolysis end-product). Since pyruvate (PYR) is structurally similar and metabolically related to LAC, we investigated the effects of PYR (aerobic glycolysis end-product) on Mb using isothermal titration calorimetry, circular dichroism, and O2-kinetic studies to evaluate PYR affinity toward Mb and to compare the effects of PYR and LAC on O2 release kinetics of oxy-Mb. Similar to LAC, PYR interacts with both oxy- and deoxy-Mb with a 1:1 stoichiometry. Time-resolved circular dichroism spectra revealed that there are no major conformational changes in the secondary structures of oxy- or deoxy-Mb during interactions with PYR or LAC. However, we found contrasting results with respect to binding affinities and substrate preference, where PYR has higher affinity toward deoxy-Mb when compared with LAC (which prefers oxy-Mb). Furthermore, PYR interaction with oxy-Mb releases a significantly lower amount of O2 than LAC. Taken together, our findings support the hypothesis that glycolytic end-products play a distinctive role in the Mb-rich tissues by serving as novel regulators of O2 availability, and/or by impacting other activities related to oxy-/deoxy-Mb toggling in resting vs. exercised or metabolically activated conditions.


 
51 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 8765: New Organic–Inorganic Salt Based on Fluconazole Drug: TD-DFT Benchmark and Computational Insights into Halogen Substitution (International Journal of Molecular Sciences)
IJMS, Vol. 23, Pages 8756: Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation (International Journal of Molecular Sciences)
 
 
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