Fatty acid 2-hydroxylase is a
protein that in humans is encoded by the FA2Hgene.[5]
Function
This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of
sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic
ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups.[5]
Mechanism of 2-hydroxylated sphingolipid generation. Essentially they are generated like their non-hydroxylated counterparts. The only difference is that fatty acids are hydroxylated by fatty acid 2-hydroxylase (FA2H) before being incorporated into dihydroceramide by ceramide synthases (CerS).
Clinical significance
Mutations in this gene have been associated with
leukodystrophy dysmyelinating with
hereditary spastic paraplegia type 35 (SPG35) with or without
dystonia[5] as well as fatty acid hydroxylase-associated neurodegeneration.[6] The largest cohort with a detailed phenotypical description and a highly sensitive imaging phenotype ('WHAT'- acronym for: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum) was recently published.[7]
FA2H has been shown to modulate
cell differentiationin vitro. FA2H is may be a
Δ9-THC-regulated gene, as Δ9-THC induces differentiation signal(s) in poorly differentiated
MDA-MB-231 cells.[8]
Fatty acid 2-hydroxylase is a
protein that in humans is encoded by the FA2Hgene.[5]
Function
This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of
sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic
ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups.[5]
Mechanism of 2-hydroxylated sphingolipid generation. Essentially they are generated like their non-hydroxylated counterparts. The only difference is that fatty acids are hydroxylated by fatty acid 2-hydroxylase (FA2H) before being incorporated into dihydroceramide by ceramide synthases (CerS).
Clinical significance
Mutations in this gene have been associated with
leukodystrophy dysmyelinating with
hereditary spastic paraplegia type 35 (SPG35) with or without
dystonia[5] as well as fatty acid hydroxylase-associated neurodegeneration.[6] The largest cohort with a detailed phenotypical description and a highly sensitive imaging phenotype ('WHAT'- acronym for: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum) was recently published.[7]
FA2H has been shown to modulate
cell differentiationin vitro. FA2H is may be a
Δ9-THC-regulated gene, as Δ9-THC induces differentiation signal(s) in poorly differentiated
MDA-MB-231 cells.[8]