Galactosylceramidase

Galactosylceramidase (GALC) (also known as galactocerebrosidase) is a hydrolase ^[1] that removes galactose from ceramide derivatives (reference). Galactosylceramidase in humans is encoded by the gene GALC, and mutations in this gene are associated with Krabbe disease, or globoid cell leukodystrophy ^[2].

Structure

X-ray diffraction data () from mouse models indicates that GALC is an estimated 77 kDa protein consisting of 656 residues, which form a secondary structure containing 12 α-helices and 41 β-strands. Each β-strand contains three to eleven residues.

Use this link to by group, and this link to view a of the protein.

Function

Disease

Defects in this enzyme cause the disease known in humans as Krabbe disease (or globoid cell leukodystrophy). Krabbe disease is a neurodegenerative disorder characterized by widespread demyelination caused by reduced or mutated function of GALC^[2]. The deficiency of GALC leads to the accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Psychosine causes the destruction of epithelial actin structures and is toxic to oligodendrocytes ^[3][4]. GALC deficiency also causes the accumulation of lipids in "globoid" macrophages, where the medical name for the disease originated ^[5]. A common authentic model for this disease is the twitcher mouse model Cite error: Invalid <ref> tag; refs with no name must have content. The only treatment currently available is an experiemental hematopoietic stem cell transplant, and gene therapies and enzyme replacements are still being researched ^[6].

Relevance