The findings, published Jan. 10, 2010 in the advance online edition of Nature Structural and Molecular Biology, suggest the possibility of a treatment to reduce the health problems associated with the enzyme defect.
"This intriguing finding could have broad public health implications," said NIAAA Acting Director Kenneth R. Warren, Ph.D. "We look forward to further research aimed at translating these laboratory discoveries into possible treatments for people."
"We recently identified a molecule called Alda-1 that activates the defective enzyme, and in the current study, we determined how this activation is achieved," said the study's senior author, Thomas D. Hurley, Ph.D., professor and associate chairman of biochemistry and molecular biology at Indiana University School of Medicine in Indianapolis. Initial investigations of Alda-1 were led by co-author Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford University School of Medicine.
After alcohol is consumed, it is first metabolized, or broken down, into acetaldehyde, a toxic chemical that causes DNA damage. Aldehyde dehydrogenase 2 (ALDH2) is the main enzyme responsible for breaking down acetaldehyde into acetate, a nontoxic metabolite in the body. It also removes other toxic aldehydes that can accumulate in the body.
About 40 percent of the East Asian population, and many people of East Asian descent throughout the world, carry a genetic mutation that produces an inactive form of ALDH2. When individuals with the ALDH2 mutation drink alcohol, acetaldehyde accumulates in the body, resulting in facial flushing, nausea, and rapid heartbeat. In addition to its link to increased cancer risk, the inactive form of ALDH2 also reduces the effectiveness of nitroglycerin. Nitroglycerin is a drug to treat angina, chest pain that occurs when the heart doesn't get enough oxygen-rich blood.
In a series of experiments that examined the interaction between Alda-1 and the defective ALDH2 enzyme, Dr. Hurley and his colleagues found that Alda-1 restored the structure of the inactive enzyme. The normal, active form of ALDH2 creates a catalytic tunnel, a space within the enzyme in which acetaldehyde is metabolized, explained Dr. Hurley. In the defective enzyme, the tunnel does not function properly. Alda-1 binds to the defective enzyme in a way that effectively reopens the catalytic tunnel and thus allows the enzyme to metabolize acetaldehyde.
"The manner in which Alda-1 binds to the structure of ALDH2 provides us with powerful insight into the relationships between activators and inhibitors of this crucial detoxifying enzyme," says Dr. Hurley. "This insight will lead to the modification of Alda-1 to improve its potency, and also opens up the possibility of designing new analogs that can selectively affect the metabolism of other molecules that are detoxified by aldehyde dehydrogenase."
The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is America's authority on alcohol research and health. The primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems, NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at www.niaaa.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIAAA Press Office | EurekAlert!
Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie
How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences