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FA2H  -  fatty acid 2-hydroxylase

Homo sapiens

 
 
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High impact information on FA2H

  • Data base searches revealed a human homologue of the yeast ceramide 2-hydroxylase gene (FAH1), which we named FA2H [1].
  • FA2H is likely involved in the formation of myelin 2-hydroxy galactosylceramides and -sulfatides [1].
  • FA2H also contains the iron-binding histidine motif conserved among membrane-bound desaturases/hydroxylases [1].
  • The amino acid sequence indicates that FA2H protein contains an N-terminal cytochrome b5 domain and four potential transmembrane domains [1].
  • The changes in free 2-hydroxy fatty acid levels coincided with fatty acid 2-hydroxylase activity and with the upregulation of FA2H expression [2].
 

Biological context of FA2H

 

Anatomical context of FA2H

  • With this method, FA2H activities were reproducibly measured in murine brains and tissue culture cell lines [5].
  • FA2H is expressed in brain, stomach, skin, kidney and testis, i.e. in tissues known to synthesize fatty acid alpha-hydroxylated sphingolipids [3].
  • Our results thus strongly suggest that FA2H is the enzyme responsible for the formation of alpha-hydroxylated ceramide in oligodendrocytes of the mammalian brain [3].
  • NADAs competitively inhibited FAAH from N18TG2 cells (IC(50)=19-100 microM), as well as the binding of the selective CB(1) receptor ligand, [(3)H]SR141716A, to rat brain membranes (K(i)=250-3900 nM) [6].
 

Associations of FA2H with chemical compounds

  • N-arachidonyl-dopamine (AA-DA) exhibited 40-fold selectivity for CB(1) (K(i)=250 nM) over CB(2) receptors, and N-docosapentaenoyl-dopamine exhibited 4-fold selectivity for the anandamide transporter over FAAH [6].
 

Analytical, diagnostic and therapeutic context of FA2H

References

  1. The human FA2H gene encodes a fatty acid 2-hydroxylase. Alderson, N.L., Rembiesa, B.M., Walla, M.D., Bielawska, A., Bielawski, J., Hama, H. J. Biol. Chem. (2004) [Pubmed]
  2. FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain. Alderson, N.L., Maldonado, E.N., Kern, M.J., Bhat, N.R., Hama, H. J. Lipid Res. (2006) [Pubmed]
  3. A mammalian fatty acid hydroxylase responsible for the formation of alpha-hydroxylated galactosylceramide in myelin. Eckhardt, M., Yaghootfam, A., Fewou, S.N., Zöller, I., Gieselmann, V. Biochem. J. (2005) [Pubmed]
  4. Conformational requirements for endocannabinoid interaction with the cannabinoid receptors, the anandamide transporter and fatty acid amidohydrolase. Reggio, P.H., Traore, H. Chem. Phys. Lipids (2000) [Pubmed]
  5. A novel method for the measurement of in vitro fatty acid 2-hydroxylase activity by gas chromatography-mass spectrometry. Alderson, N.L., Walla, M.D., Hama, H. J. Lipid Res. (2005) [Pubmed]
  6. N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Bisogno, T., Melck, D., Bobrov MYu, n.u.l.l., Gretskaya, N.M., Bezuglov, V.V., De Petrocellis, L., Di Marzo, V. Biochem. J. (2000) [Pubmed]
 
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