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.

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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 Cite error: Invalid <ref> tag; refs with no name must have content. 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 Cite error: Invalid <ref> tag; refs with no name must have content.

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