Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U of I scientist develops enzyme inhibitor that may slow cancer growth

10.07.2006
Urbana –University of Illinois scientist Tim Garrow, in collaboration with Jiri Jiracek of the Czech Academy of Sciences, has applied for a provisional patent on a class of chemicals that has future therapeutic uses in medicine, specifically cancer treatment.

"These chemicals are potent inhibitors of an enzyme called betaine-homocysteine-S-methyltransferase (BHMT)," said Garrow.

"BHMT catalyzes a reaction that converts homocysteine to methionine. Because cancer cells require high levels of methionine, the ability to slow methionine's production could result in a treatment that will selectively inhibit cancer growth," the U of I professor of nutrition said.

Methionine, an essential amino acid, is required for several important biological processes, including synthesis of a compound that cancer cells require more than other cells. "When scientists restrict dietary methionine in animals with cancer, cancer cells are more acutely affected than others," Garrow said.

Many drugs work by inhibiting the action of an enzyme, including the statin drugs used to lower cholesterol, he added.

Garrow became interested in BHMT, which is abundant in the liver and present in lesser amounts in the kidneys, because elevated levels of blood homocysteine have been linked with a number of diseases, including vascular disease and thrombosis.

"Our lab has always been interested in BHMT's role in modulating plasma homocysteine, and we've engaged in some productive research collaborations. Martha Ludwig's lab at the University of Michigan solved BMHT's crystal structure.

"That breakthrough enabled us to look at the enzyme in three dimensions, which helped us design inhibitors for it. Several of those compounds were very effective in blocking binding of the enzyme's normal substrates," he said.

Injecting one of these BHMT inhibitors into the abdomens of mice resulted in changes in metabolite concentrations and elevated levels of homocysteine in the animals, showing that "our chemical inhibitor made its way from the abdominal cavity into the mouse's liver, where the inhibitor blocked the BHMT-catalyzed reaction as we thought it would."

Garrow believes BHMT inhibitors may work best in concert with other drugs. "In today's medicine, there's rarely one magic-bullet drug. We know that when you decrease the availability of methionine to cancer cells, another cancer drug called cisplatin works better. So a drug that inhibits BHMT, which decreases methionine availability, may well enhance the efficacy of another cancer treatment drug," he said.

Elevated levels of homocysteine could be a negative side effect of such therapy, but Garrow said the benefits of the drug would likely outweigh the risk. "A cancer patient would probably take the BMHT inhibitor for a limited time, while vascular disease--associated with high homocysteine levels--progresses over the course of a lifetime."

Garrow believes another therapeutic application for BHMT inhibitors could involve betaine, one of the enzyme's substrates.

"When you inhibit BHMT, you also block the utilization of betaine. Betaine not only donates a methyl group to homocysteine to form methionine, it also functions as an osmolyte, helping to regulate water content in the cells. We think the BHMT inhibitor could also be medically useful when there is unwanted diuresis or unwanted loss of water," he said.

Garrow's work with BHMT in mice was published in the June issue of the Journal of Nutrition. Co-authors include Michaela Collinsova, Jana Strakova, and Jiri Jiracek of the Academy of Sciences of the Czech Republic.

Phyllis Picklesimer | EurekAlert!
Further information:
http://www.uiuc.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>