Rowena G. Matthews
University of Michigan
Election Year: 2002
Primary Section: 21, Biochemistry
Secondary Section: 29, Biophysics and Computational Biology
Membership Type: Member
My major research interest is the roles of vitamin-derived cofactors in the catalysis of complex chemical reactions. My laboratory has concentrated on cofactors derived from vitamin B12 (cobalamin) and folic acid, which are involved in cellular one-carbon metabolism. Cobalamin plays an important role in one carbon metabolism by accepting a methyl group from a derivative of folic acid, methyltetrahydrofolate, and delivering it to homocysteine to form methionine. Elevated levels of plasma homocysteine are linked to increased incidence of cardiovascular disease and to development of neural tube defects in the fetus. We have studied enzymes involved in homocysteine remethylation that employ cobalamin- and folate-based cofactors to gain insights into the chemistry of the transformations, as well as to delineate the molecular consequences of genetic variations that are known to lead to elevated levels of plasma homocyseine when folate levels are low. In addition, we are interested in the factors that govern the conformation changes necessary for alternate exposure of methyltetrahydrofolate and homocysteine to the cobalamin cofactor during the synthesis of methionine. We are exploring how substrate and product binding and the changing methylation state of the cobalamin bias the kinetics and thermodynamics governing interconversion of conformational states of the enzyme.