Galactosemia is a rare, inherited metabolic disease which results from mutations in the genes encoding enzymes of galactose metabolism. The mildest cases are almost asymptomatic, but the most severe are life-threatening. There is no cure. We are seeking to understand the molecular basis of this disease by studying recombinant enzymes from the Leloir pathway of galactose metabolism. Typically we recapitulate disease-associated variants and study the biochemical and enzymological effects. In addition, we also conduct in silico studies. The dramatic effects of severe forms of galactosemia suggest that inhibition of these enzymes in pathogens may be a viable strategy for therapy. Therefore, we have studied some of these enzymes from parasitic worms with a longer term aim of identifying novel inhibitors of these enzymes. We have also attempted to expand the substrate range of galactokinase so that it can be used in the biocatalytic site- and stereo-specific phosphorylation ofa range of monosaccharides.
The work is conducted with a range of excellent collaborators and we are always open to new collaborations. We are also interested in extending the approaches taken to understand galactosemia to other inherited metabolic diseases.
This project commenced in 2001 and will end when we fully understand the molecular basis of galactosemia.
Dr Angel Pey, University of Grenada
Prof Estela Rubio-Gozalbo, University of Maastricht