Lipid of the Month

Each month we highlight a lipid of scientific interest. The LIPID MAPS® Lipid of the Month Archive lists lipids highlighted from 2015 - present.

February 2023

Lipid of the month Psychosine

Over 100 years ago, Krabbe and Copenhagen described a rare inherited neurological condition which would become known as globoid cell leukodystrophy, or Krabbe disease1. It’s now known to be characterized by an accumulation of the lipid psychosine in the membranes of cells such as Schwann cells and oligodendrocytes in the nervous system. It leaves these cells unable to provide the myelination around nerve axons which is necessary for nerve function.

Psychosine accumulates due to a deficiency in an enzyme encoded by the GALC gene. The most common mutations in GALC cause a form of Krabbe disease which is usually fatal in infancy, though some mutations result in an adult-onset phenotype2. GALC encodes galactocerebrosidase which ordinarily cleaves the galactose headgroup from galactoceramides (for example, from (GalCer d18:1/16:0)  in their degradation pathway. In its absence, the acyl chain of the molecule can be removed by acid ceramidase, leaving galactosyl-sphingosine, or psychosine, behind.

Evidence suggests that build up of psychosine, essentially ‘lyso’ galactosylceramide, disrupts the properties of the membrane3 (ref) which may contribute to the disease phenotype.

While Krabbe disease was described in 1916, psychosine was described much earlier. It was mentioned by Thudichum in 1884 in his treatise on the chemical constitution of the brain. Presumably it was named after its isolation from brain extracts (psycho- referring to the mind). The link between psychosine and Krabbe disease was made fifty years ago in 19724.

References

  • A New Familial, Infantile Form Of Diffuse Brain-Sclerosis
    Brain
    1916
    DOI 10.1093/brain/39.1-2.74
  • A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review
    Neurogenetics
    2022
    DOI 10.1007/s10048-021-00682-1
  • Psychosine, the cytotoxic sphingolipid that accumulates in globoid cell leukodystrophy, alters membrane architecture
    J Lipid Res
    2013
    DOI 10.1194/jlr.M039610
  • Globoid cell leukodystrophy: Additional deficiency of psychosine galactosidase
    Biochem Biophys Res Commun
    1972
    DOI 10.1016/0006-291X(72)90381-6

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