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 ele
Contact: Phyllis Picklesimer
University of Illinois at Urbana-Champaign