Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery of enzyme activation process could lead to new heart attack treatments

11.01.2010
Researchers at the Indiana University and Stanford University schools of medicine have determined how a "chemical chaperone" does its job in the body, which could lead to a new class of drugs to help reduce the muscle damage caused by heart attacks.

Such drugs would work by restoring the activity of a mutated enzyme, rather than taking the more common approach of blocking the actions of a disease-related protein.

The team, led by Thomas Hurley, Ph.D., associate chair and professor of biochemistry and molecular biology at IU, and Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford, report in the journal Nature Structural Biology published online Jan. 10 that the compound, called Alda-1, acts much like a shim to prop up a mutated form of a key enzyme, restoring the enzyme's function.

The enzyme, called ALDH2, plays an important role in metabolizing alcohol and other toxins, including those created by a lack of oxygen in the wake of a heart attack. It also is involved in the metabolism of nitroglycerin, which is used to prevent chest pain (angina) caused by restricted blood flow and oxygen to the heart.

However some people, including about 40 percent of people of East Asian descent, carry a mutated form of the ALDH2 enzyme that does not carry out its intended functions well. People with the mutated form of the enzyme are at increased risk of cardiovascular damage.

The IU and Stanford team reported in 2008 in the journal Science that in laboratory tests Alda-1 bypassed the body's usual signaling system and activated the ALDH2 enzyme directly, reducing damage to heart muscle tissue. That finding raised the possibility of new treatments for heart attacks, methods to protect hearts during open heart surgery, organ transplants, stroke and other situations in which blood flow is interrupted.

Their current paper describes how Alda-1 activates the ALDH2 enzyme in a process that Dr. Hurley likens to a woodworking procedure in which Alda-1 attaches to the ALDH2 enzyme at a crucial spot and acts like a shim or wedge to prop it up.

"Because of the mutation in the gene, parts of the protein structure become loose and floppy. Alda-1 reactivates the enzyme by propping up those parts of the structure so they regain normal function," said Dr. Hurley, director of the Center for Structural Biology on the Indiana University-Purdue University Indianapolis campus.

Determining how the Alda-1 compound works will enable the researchers to begin working on alternative compounds that hold more promise as potential drugs. One primary improvement needed is the ability to give the drug orally, rather than by injection, Dr. Hurley said.

"Based on the information from these studies, we're now ready to sit down with medicinal chemists and start designing new analogues by applying our understanding of what we need to leave alone and what we can modify to improve the properties of Alda-1," he said.

He predicted that alternative compounds could be available for testing by mid-2010.

The research was supported by grants from the National Institute of Alcohol Abuse and Alcoholism at the National Institutes of Health.

Eric Schoch | EurekAlert!
Further information:
http://www.iupui.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>