Natures wonders: mitochondria living with oxygen stress (Introduction)

by David Turell , Tuesday, April 06, 2021, 20:53 (1325 days ago) @ David Turell

To live we we create energy by using oxygen resulting in byproducts of oxygen, like super oxygen, one of the reactive oxygen species, that can badly damage cells. Mitochondria nave a special protective enzyme:

https://phys.org/news/2021-04-reveal-elusive-antioxidant-enzyme-therapeutic.html

"Mitochondria, known as the powerhouses within human cells, generate the energy needed for cell survival. However, as a byproduct of this process, mitochondria also produce reactive oxygen species (ROS). At high enough concentrations, ROS cause oxidative damage and can even kill cells.

"An enzyme called manganese superoxide dismutase, or MnSOD, uses a mechanism involving electron and proton transfers to lower ROS levels in mitochondria, thus preventing oxidative damage and maintaining cell health. More than a quarter of known enzymes also rely on electron and proton transfers to facilitate cellular activities that are essential for human health.

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"MnSOD works by targeting superoxide, a reactive molecule that leaks from the mitochondrial energy production process and is the chemical precursor for other harmful ROS. The enzyme's active site turns superoxide into less toxic products by using its manganese ion to move electrons to and from the reactive molecule. The manganese ion is capable of stealing an electron from a superoxide molecule, converting it to oxygen. This stolen electron can then be given to another superoxide to make hydrogen peroxide.

"For this biochemical reaction to work, a series of proton movements need to take place between the enzyme's amino acids and other molecules at its active site. The protons act as instruments that enable the electrons to move. Until now, the enzyme's sequence of electron and proton transfers, also known as its catalytic mechanism, had not been defined at the atomic level because of challenges in tracking how protons are shuttled between molecules. A fundamental understanding of this catalytic process could inform therapeutic approaches that harness this enzyme's antioxidant abilities.

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"Their analysis suggests that catalysis involves two internal proton transfers between the enzyme's amino acids and two external proton transfers that originate from solvent molecules. While the results of this study confirm some past predictions of the enzyme's biochemical nature, several aspects were unexpected and challenge previously held beliefs.

"For example, the team uncovered cyclic proton transfers occurring between a glutamine amino acid and a manganese-bound solvent molecule. This interaction is a central part of the catalytic process, as it allows the enzyme to cycle between its two electronic states. The researchers also found the proton movements within the active site to be unusual, as several amino acids did not have a proton where they normally would. The study demonstrates the dramatic effects a metal has on the chemistry of the active site that is usually not accounted for.

"'Our results suggest that this mechanism is more complex and atypical than what past studies had theorized," said Jahaun Azadmanesh, a researcher at UNMC and study co-author."

Comment: Step back and view the whole picture of evolution. At a point the Earth is flooded with oxygen and organisms begin to use it to create energy to sustain life, despite how dangerous it is. Logically Oxygen's use and the antioxidant protections had to develop simultaneously. Not by chance, it had to be designed.