Molybdenum oxide particles can assume the function of the endogenous enzyme sulfite oxidase / Basis for new therapeutic application
Scientists at Johannes Gutenberg University Mainz (JGU) in Germany have discovered that molybdenum trioxide nanoparticles oxidize sulfite to sulfate in liver cells in analogy to the enzyme sulfite oxidase. The functionalized Molybdenum trioxide nanoparticles can cross the cellular membrane and accumulate at the mitochondria, where they can recover the activity of sulfite oxidase.
Sulfite oxidase is a molybdenum containing enzyme located in the mitochondria of liver and kidney cells, which catalyzes the oxidation of sulfite to sulfate during the protein and lipid metabolism and therefore plays an important role in cellular detoxification processes.
A lack of functional sulfite oxidase is a rare but fatal genetic disease causing neurological disorders, mental retardation, physical deformities as well as degradation of the brain, which finally leads to premature death. Various dietary or drug treatments for a sulfite oxidase deficiency have been tried with moderate success.
It was the fact that molybdenum oxide is incorporated in the enzymes active site that provided the inspiration for the approach now taken by the team of scientists working under the lead of Professor Wolfgang Tremel of the JGU Institute of Inorganic Chemistry and Analytical Chemistry as well as Dr. Dennis Strand and Professor Susanne Strand of the Department of Internal Medicine of the Mainz University Medical Center. The researchers hope that this study may lay the basis for a therapeutic application of molybdenum trioxide nanoparticles and therefore new possibilities to treat sulfite oxidase deficiency.
Lowered sulfite oxidase levels can cause health problems even for otherwise healthy persons. In addition, sulfites are used as preservatives in food, e.g., in red wine, grape juice, or pickles in a jar. People having low levels of the sulfite oxidase react with symptoms like fatigue, asthma, drop in blood sugar, or headache.
With their study the Mainz scientists enter scientifically uncharted territory, because so far there are just a few studies of enzymatically active nanoparticles. "It is indeed astonishing, that simple inorganic nanoparticles can mimic an enzymatic activity," said Ruben Ragg, first author of this study.
In a previous work Professor Wolfgang Tremel and his team had shown that vanadium oxide nanowires contain an enzymatically induced antifouling activity that efficiently prevents ships from being infested by marine microorganisms. "It is a long-standing goal of chemistry to synthesize artificial enzymes that imitate the essential and general principles of natural enzymes," added Tremel.
There is growing evidence that nanoparticles can act as enzyme mimics. Some nanomaterials were reported to exhibit enzyme-like activities, but the hallmark of enzyme chemistry would be to catalyze transformations in cells in the presence of other competing reactions.
This is difficult to achieve, as it requires compatibility with other cellular reactions operating under similar conditions and rates. Therefore, artificial enzymes are not only useful for an understanding of the reaction mechanism of native enzymes but also for future applications as therapeutic agents.
At the same time, the use of molybdenum nanoparticles would have several benefits. "Molybdenum oxide particles are considerably cheaper and also more stable than genetically produced enzymes," added Dr. Filipe Natalio, cooperation partner from Martin Luther University of Halle-Wittenberg.
Natalio is designing new materials that can mimic complex structures found in nature by bringing together a wide range expertise from material sciences to biology and chemistry. The next steps of the project will be to test if the enzyme activity of the nanoparticles can be retained in living organisms.
The research teams were supported by an interdisciplinary grant from the JGU Center for Natural Sciences and Medicine (NMFZ) and the Max Planck Graduate Center (MPGC).
Ruben Ragg, et al.
Molybdenum Trioxide Nanoparticles with Intrinsic Sulfite Oxidase Activity
ACS Nano 2014, 8 (5), pp. 5182–5189, 4 April 2014
Professor Wolfgang Tremel
Institute of Inorganic Chemistry and Analytical Chemistry
Johannes Gutenberg University Mainz (JGU)
55099 Mainz, GERMANY
phone +49 6131 39-25135
fax +49 6131 39-25605
Dr. Dennis Strand, Professor Susanne Strand
Department of Internal Medicine
Mainz University Medical Center
Johannes Gutenberg University Mainz (JGU)
55131 Mainz, GERMANY
phone + 49 6131 17-9782
e-mail: firstname.lastname@example.org // email@example.com
http://pubs.acs.org/doi/abs/10.1021/nn501235j - Article ;
http://www.uni-mainz.de/presse/15482_ENG_HTML.php - press release "Inspired by nature: Paints and coatings containing bactericidal agent nanoparticles combat marine fouling", 2 July 2012
Petra Giegerich | idw - Informationsdienst Wissenschaft
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Life Sciences
17.07.2018 | Information Technology
17.07.2018 | Power and Electrical Engineering