galactosylceramide

Galactosylceramide, also called galactocerebroside, is a glycosphingolipid consisting of a galactose headgroup linked to a ceramide backbone. It is a major component of myelin in the central nervous system and is enriched in the membranes of oligodendrocytes and Schwann cells, contributing to myelin sheath stability and compactness that insulates nerve fibers.

Biochemistry and biosynthesis: Galactosylceramide is synthesized in the Golgi apparatus by the enzyme UDP-galactose:ceramide galactosyltransferase, encoded by the UGT8 gene. This enzyme transfers galactose from UDP-galactose to ceramide to form GalCer. The molecule can serve as a precursor for related lipids such as sulfatide, a sulfated derivative of galactosylceramide.

Functions: As a structural lipid, GalCer participates in the organization of the myelin membrane and may play roles in cell signaling and glial-neuronal interactions. Its exact physiological functions are still being investigated, but its presence supports myelin integrity and membrane architecture in myelinating cells.

Clinical significance: Impaired metabolism of galactosylceramide in lysosomes, due to deficiency of the hydrolase galactosylceramidase (GALC), causes Krabbe disease (globoid cell leukodystrophy), a severe pediatric demyelinating disorder. Accumulation of GalCer and psychosine contributes to progressive neurodegeneration, demyelination, and early mortality, underscoring the importance of GalCer turnover for myelin maintenance.