"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!
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences