Verhandelingen - Koninklijke Academie voor Geneeskunde van België vol:68 issue:3 pages:199-221; discussion 221-2
Peroxisomes have an important role in lipid metabolism e.g. beta-oxidation of long and very long chain fatty acids, 2-methyl-branched fatty acids, dicarboxylic fatty acids, prostanoids and bile acid intermediates, and synthesis of ether lipids. Also the process of alpha-oxidation of 3-methyl-branched fatty acids, with phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) as the best known example, occurs in peroxisomes. alpha-Oxidation is a process in which fatty acids are shortened by one carbon atom. The alpha-oxidation sequence of 3-methyl-branched fatty acids starts with an activation to the corresponding CoA-ester. Subsequently this acyl-CoA-ester undergoes a 2-hydroxylation by the peroxisomal phytanoyl-CoA hydroxylase (PAHX). In a third step the peroxisomal 2-hydroxyphytanoyl-CoA lyase (2-HPCL) splits the carbon carbon bond of the 2-hydroxy-intermediate into a 2-methyl(n-1)aldehyde and formyl-CoA, which is subsequently converted to formate and CO2. Finally the aldehyde is dehydrogenated by an aldehyde dehydrogenase to the corresponding acid, which, after its conversion to the acyl-CoA ester, can be a substrate for beta-oxidation. 2-HPCL is the first thiamine pyrophosphate dependent peroxisomal enzyme in mammals. Apart from 2-hydroxy-3-methylacyl-CoAs also 2-hydroxyacyl-CoAs are substrates for this enzyme. This indicates that the 2-hydroxy function but not the 3-methyl function of acyl-CoA esters is needed for 2-HPCL-activity. Long and very long chain 2-hydroxy fatty acids are constituents of brain cerebrosides and sulfatides, which mainly occur in myelin.