"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!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences