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 For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>