Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists take 'snapshots' of enzyme action

14.06.2006
Results advance understanding of how toxic compounds are eliminated from the body

Scientists at the U.S. Department of Energy's Brookhaven National Laboratory, the New York Structural Biology Center, and SGX Pharmaceuticals, Inc., have determined the atomic crystal structure and functional mechanism of an enzyme essential for eliminating unwanted, non-nutritional compounds such as drugs, industrial chemicals, and toxic compounds from the body. The detailed mechanism of action will help scientists understand how these compounds are eliminated and what goes wrong in cases where normal metabolism fails. The research will be published online the week of June 12, 2006, by the Proceedings of the National Academy of Sciences.

According to Brookhaven biologists Eswaramoorthy Subramaniam, the lead author, and Subramanyam Swaminathan, who led the research, most non-nutritional, foreign substances such as drugs and industrial chemicals are insoluble in water. The body uses two main groups of enzymes -- flavin-containing monooxygenases (FMOs) and cytochrome P450s -- to convert these compounds to soluble forms that can be easily excreted.

"For FMOs, the end result -- that an oxygen atom gets added to make these compounds soluble -- is simple," Swaminathan says, "but the reactions require additional participants, or cofactors." In order to understand the molecular mechanism, the scientists used high-intensity x-ray beams at the National Synchrotron Light Source (NSLS) to identify the positions of individual atoms and produce crystal structures of the enzyme, the enzyme plus its cofactor, and the enzyme plus the cofactor plus the compound to be oxidized (the substrate).

"These crystal structures give step-by-step snapshots of different stages of the catalytic action," Swaminathan says, "and reveal a mechanism that is different from what had been known about this process."

Previously, it had been believed that all the "players" -- the enzyme, cofactor, and substrate -- came together at a particular time to perform the function of transferring an oxygen atom from the enzyme to the substrate. "Our finding shows that the substrate and cofactor are binding to the enzyme alternately, not together," Swaminathan says.

First, the cofactor (known as NADPH) binds to a molecule known as FAD, which is a coenzyme attached to the FMO, and transfers a hydride ion to it. That makes the FAD group capable of accepting molecular oxygen. Then, when the substrate arrives, the cofactor leaves so that the substrate can bind to the same site on the FAD group. At this moment an oxygen atom from molecular oxygen is attached to the substrate, and the hydride ion obtained from the cofactor combines with the other oxygen atom to form a water molecule, which is released. Once the substrate is oxygenated, it leaves the enzyme and the cofactor binds again.

"With this back-and-forth, alternating binding, the process repeats over and over for continuous turnover of the product," Swaminathan says.

The details of this process may help scientists understand what happens in cases where compounds are not properly metabolized, and possibly develop corrective measures.

One example is a condition called trimethylaminuria, also known as "fish odor syndrome," which results from defective FMOs. Affected individuals are unable to oxygenate trimethylamine, a byproduct of protein digestion released by bacteria living in the gut. People with the disorder release trimethylamine through breath, sweat, and urine, producing a fish-like odor that can be embarrassing and result in psychological effects such as withdrawal and depression.

People with defective FMOs might also suffer additional side effects from drugs, industrial compounds, or other chemicals.

Karen McNulty Walsh | EurekAlert!
Further information:
http://www.bnl.gov

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>