Fatty Acid 2-Hydroxylation in Mammalian Sphingolipid Biology

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2009 Dec 23

PMID 20026285

Citations 101

Authors

Hiroko Hama

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Date palm diverts organic solutes for root osmotic adjustment and protects leaves from oxidative damage in early drought acclimation.

Franzisky B, Mueller H, Du B, Lux T, White P, Carpentier S J Exp Bot. 2024; 76(4):1244-1265.

PMID: 39521950 PMC: 11850976. DOI: 10.1093/jxb/erae456.

2-Hydroxylation is a chemical switch linking fatty acids to glucose-stimulated insulin secretion.

Li H, Lin L, Huang X, Lu Y, Su X J Biol Chem. 2024; 300(12):107912.

PMID: 39442620 PMC: 11742320. DOI: 10.1016/j.jbc.2024.107912.

Illuminating the dark space of neutral glycosphingolipidome by selective enrichment and profiling at multi-structural levels.

Wang Z, Zhang D, Wu J, Zhang W, Xia Y Nat Commun. 2024; 15(1):5627.

PMID: 38965283 PMC: 11224418. DOI: 10.1038/s41467-024-50014-8.

Sphingolipids: Less Enigmatic but Still Many Questions about the Role(s) of Ceramide in the Synthesis/Function of the Ganglioside Class of Glycosphingolipids.

Schengrund C Int J Mol Sci. 2024; 25(12).

PMID: 38928016 PMC: 11203820. DOI: 10.3390/ijms25126312.

Fatty Acid Metabolism in Peroxisomes and Related Disorders.

Morito K, Ali H, Kishino S, Tanaka T Adv Exp Med Biol. 2024; 1470:31-55.

PMID: 38811487 DOI: 10.1007/5584_2024_802.

References

Bouhours D, Bouhours J . Developmental changes of hematoside of rat small intestine. Postnatal hydroxylation of fatty acids and sialic acid. J Biol Chem. 1983; 258(1):299-304. View

Dahiya R, Brown M, Brasitus T . Distribution of glycosphingolipids of monkey small and large intestinal mucosa. Lipids. 1986; 21(2):107-11. DOI: 10.1007/BF02534429. View

Pascher I . Molecular arrangements in sphingolipids. Conformation and hydrogen bonding of ceramide and their implication on membrane stability and permeability. Biochim Biophys Acta. 1976; 455(2):433-51. DOI: 10.1016/0005-2736(76)90316-3. View

Llado V, Gutierrez A, Martinez J, Casas J, Teres S, Higuera M . Minerval induces apoptosis in Jurkat and other cancer cells. J Cell Mol Med. 2009; 14(3):659-70. PMC: 3823464. DOI: 10.1111/j.1582-4934.2008.00625.x. View

Holleran W, Takagi Y, Uchida Y . Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett. 2006; 580(23):5456-66. DOI: 10.1016/j.febslet.2006.08.039. View

Okazaki T, Bell R, Hannun Y . Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. J Biol Chem. 1989; 264(32):19076-80. View

Robinson B, Johnson D, Poulos A . Novel molecular species of sphingomyelin containing 2-hydroxylated polyenoic very-long-chain fatty acids in mammalian testes and spermatozoa. J Biol Chem. 1992; 267(3):1746-51. View

Angstrom J, Teneberg S, Milh M, Larsson T, Leonardsson I, Olsson B . The lactosylceramide binding specificity of Helicobacter pylori. Glycobiology. 1998; 8(4):297-309. DOI: 10.1093/glycob/8.4.297. View

Rauvala H . Gangliosides of human kidney. J Biol Chem. 1976; 251(23):7517-20. View

10.

Sprong H, Kruithof B, Leijendekker R, Slot J, van Meer G, van der Sluijs P . UDP-galactose:ceramide galactosyltransferase is a class I integral membrane protein of the endoplasmic reticulum. J Biol Chem. 1998; 273(40):25880-8. DOI: 10.1074/jbc.273.40.25880. View

11.

MARTENSSON E . Neutral glycolipids of human kidney isolation, identification, and fatty acid composition. Biochim Biophys Acta. 1966; 116(2):296-308. DOI: 10.1016/0005-2760(66)90012-9. View

12.

Ji L, Zhang G, Uematsu S, Akahori Y, Hirabayashi Y . Induction of apoptotic DNA fragmentation and cell death by natural ceramide. FEBS Lett. 1995; 358(2):211-4. DOI: 10.1016/0014-5793(94)01428-4. View

13.

Riboni L, Acquotti D, Casellato R, Ghidoni R, MONTAGNOLO G, Benevento A . Changes of the human liver GM3 ganglioside molecular species during aging. Eur J Biochem. 1992; 203(1-2):107-13. DOI: 10.1111/j.1432-1033.1992.tb19834.x. View

14.

Morrison W, Hay J . Polar lipids in bovine milk. II. Long-chain bases, normal and 2-hydroxy fatty acids, and isomeric cis and trans monoenoic fatty acids in the sphingolipids. Biochim Biophys Acta. 1970; 202(3):460-7. DOI: 10.1016/0005-2760(70)90116-5. View

15.

Uchida Y, Hama H, Alderson N, Douangpanya S, Wang Y, Crumrine D . Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation. J Biol Chem. 2007; 282(18):13211-9. DOI: 10.1074/jbc.M611562200. View

16.

Seyfried T, Ando S, Yu R . Isolation and characterization of human liver hematoside. J Lipid Res. 1978; 19(5):538-43. View

17.

Bouhours D, Bouhours J . Developmental changes of monohexosylceramide and free ceramide in the large intestine of the rat. J Biochem. 1985; 98(5):1359-66. DOI: 10.1093/oxfordjournals.jbchem.a135403. View

18.

Sugita M, Iwamori M, Evans J, McCluer R, DULANEY J, Moser H . High performance liquid chromatography of ceramides: application to analysis in human tissues and demonstration of ceramide excess in Farber's disease. J Lipid Res. 1974; 15(3):223-6. View

19.

Sugita M, Connolly P, DULANEY J, Moser H . Fatty acid composition of free ceramides of kidney and cerebellum from a patient with Farber's disease. Lipids. 1973; 8(7):401-6. DOI: 10.1007/BF02531715. View

20.

Binnington B, Lingwood D, Nutikka A, Lingwood C . Effect of globotriaosyl ceramide fatty acid alpha-hydroxylation on the binding by verotoxin 1 and verotoxin 2. Neurochem Res. 2002; 27(7-8):807-13. DOI: 10.1023/a:1020261125008. View