Fatty acid 2-Hydroxylation in mammalian sphingolipid biology

Biochim Biophys Acta. 2010 Apr;1801(4):405-14. doi: 10.1016/j.bbalip.2009.12.004. Epub 2009 Dec 21.


2-Hydroxy fatty acids (hFA) are important components of a subset of mammalian sphingolipids. The presence of hFA in sphingolipids is best described in the nervous system, epidermis, and kidney. However, the literature also indicates that various hFA-sphingolipids are present in additional tissues and cell types, as well as in tumors. Biosynthesis of hFA-sphingolipids requires fatty acid 2-hydroyxlase, and degradation of hFA-sphingolipids depends, at least in part, on lysosomal acid ceramidase and the peroxisomal fatty acid alpha-oxidation pathway. Mutations in the fatty acid 2-hydroxylase gene, FA2H, have been associated with leukodystrophy and spastic paraparesis in humans, underscoring the importance of hFA-sphingolipids in the nervous system. In the epidermis, hFA-ceramides are essential for the permeability barrier function. Physiological function of hFA-sphingolipids in other organs remains largely unknown. Recent evidence indicates that hFA-sphingolipids have specific roles in cell signaling.

Keywords: FA2H; Fatty acid 2-hydroxylase; fatty acid alpha-hydroxylase; hydroxy fatty acid; hydroxy sphingolipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Fatty Acids / metabolism*
  • Humans
  • Hydroxylation
  • Mixed Function Oxygenases / metabolism*
  • Sphingolipids / metabolism*


  • Fatty Acids
  • Sphingolipids
  • Mixed Function Oxygenases
  • fatty acid alpha-hydroxylase