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Research Project: Impact of Maternal Influence and Early Dietary Factors on Child Growth, Development, and Metabolic Health

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Title: Myoglobin-pyruvate interaction: thermodynamic binding, structure-function relationship and oxygen kinetic studies

item ADEPU, KIRAN KUMAR - Arkansas Children'S Nutrition Research Center (ACNC)
item BHANDARI, DIPENDRA - Arkansas Children'S Nutrition Research Center (ACNC)
item ANISHKIN, ANDRIY - University Of Maryland
item ADAMS, SEAN - University Of California, Davis
item CHINTAPALLI, SREE - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2022
Publication Date: 8/6/2022
Citation: Adepu, K., Bhandari, D., Anishkin, A., Adams, S.H., Chintapalli, S.V. 2022. Myoglobin-pyruvate interaction: thermodynamic binding, structure-function relationship and oxygen kinetic studies. International Journal of Molecular Sciences. 23(15):8766.

Interpretive Summary: Myoglobin (Mb), a protein found in muscle tissues plays an important role in storing and transporting the oxygen to mitochondria in the cells. It is also known to transport the end products of cellular metabolism like fatty acids, lactate (LAC) in the cells. During exercise and hypoxic conditions, cells need more oxygen for burning glucose to produce extra energy. We have recently shown that the presence of LAC and its interaction with Mb increased the oxygen levels. As LAC and pyruvate (PYR) are glycoloytic end-products and are similar in structure, we hypothesized that PYR can also interact with Mb and show similar effect. In this study, we found that PYR also interacts with Mb and releases oxygen in the cells. However, the oxygen release rate of PYR is less than that of LAC. Additionally, when Mb releases oxygen, it goes to a state called deoxy-myoglobin. Our studies shows that PYR has stronger interaction with deoxy-myoglobin whereas LAC has stronger interaction with oxy-myoglobin. This preferential binding of LAC and PYR may have influence in mediating the availability of oxygen during the exercise conditions.

Technical Abstract: Myoglobin (Mb), besides its role as an oxygen(O2) carrier/storage function, and Nitric Oxide NO scavenger, it has also gained importance as fatty acid transporter. However, our recent find-ings have shown that increased levels of O2 were observed during lactate (LAC) interaction (anerobic glycolysis end-product) with oxy-Mb. As pyruvate (PYR) is structurally similar to LAC, we investigated the effects of PYR (aerobic glycolysis end-product) on Mb using isother-mal titration calorimetry, circular dichroism, and O2-kinetic studies to evaluate PYR affinity to-wards Mb and concomitantly compare the effects of both PYR and LAC on O2 release kinetics during interaction with oxy-Mb. Like LAC interaction with Mb, PYR also 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 structure both oxy- and deoxy-Mb structures during the interaction of either PYR or LAC interaction. However, we found con-trasting results with respect to binding affinities and substrate preference, where PYR has higher affinity towards deoxy-Mb when compared with LAC (which prefers oxy-Mb). Furthermore, our results have also indicated that PYR interaction with oxy-Mb releases less amount of O2 than LAC. Taken together, our findings support a mechanism in which glycolytic end-products play a distinctive role in the Mb-rich tissues and may act as novel regulators for O2 availability during resting vs exercise conditions.