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 Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>