Add time:09/09/2019         Source:sciencedirect.com

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid which cannot be beta-oxidized due to the presence of the first methyl group at the 3-position. Instead, phytanic acid undergoes alpha-oxidation to produce pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) plus CO2. Pristanic acid is a 2-methyl branched-chain fatty acid which can undergo beta-oxidation via sequential cycles of beta-oxidation in peroxisomes and mitochondria. The mechanism of alpha-oxidation has been resolved in recent years as reviewed in this paper, although some of the individual enzymatic steps remain to be identified. Furthermore, much has been learned in recent years about the permeability properties of the peroxisomal membrane with important consequences for the alpha-oxidation process. Finally, we present new data on the omega-oxidation of phytanic acid making use of a recently generated mouse model for Refsum disease in which the gene encoding phytanoyl-CoA 2-hydroxylase has been disrupted.

► 3-Methyl branched-chain fatty acids can be oxidized by α- and/or ω-oxidation. ► The mechanism, enzymology and subcellular localization of α-oxidation has largely be resolved. ► The peroxisomal membrane is a semi-permeable membrane allowing the transport of some, but not all substrates and products of α-oxidation. ► The enzymology of the phytanic acid ω-oxidation has largely been resolved. ► Stimulation of ω-oxidation by bezafibrate reduces the accumulation of phytanic acid in Refsum mice.

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