Dr. Berge A. Minassian
MD, Chief of Pediatric Neurology, UT Southwestern Medical Center
Department of Pediatrics, Division of Neurology
With several Nobel prizes along the way, glycogen construction was thought to be settled science. Namely, glycogen synthase elongates chains, which glycogen branching enzyme cleaves and reattaches upstream, and balanced activities of the two enzymes ensures radial growth of the molecule and solubility. Lafora disease is a fatal neurodegenerative disease of children in whom glycogen is malstructured. Long-chained, its strands fold round each other, exclude water, precipitate, and accumulate into massive neurotoxic Lafora bodies. We have discovered the disease genes, which encode the laforin glycogen phosphatase and the malin ubiquitin E3 ligase. In this lecture, I present the latest advances in our understanding of how these enzymes regulate glycogen structure, ensuring its sphericity and molecule-through hydro-perfusion, which allows the cytoplasm’s largest macromolecule to remain soluble, and accessible to metabolism.