2-Hydroxyphytanoyl-CoA lyase (abbreviated as 2-HPCL), renamed to 2-hydroxyacyl-CoA lyase (abbreviated as HACL1), is the first peroxisomal enzyme in mammals that has been found to be dependent on TPP (thiamin pyrophosphate). It was discovered in 1999, when studying α-oxidation of phytanic acid. HACL1 has an important role in at least two pathways: (i) the degradation of 3-methyl-branched fatty acids like phytanic acid and (ii) the shortening of 2-hydroxy long-chain fatty acids. In both cases, HACL1 catalyses the cleavage step, which involves the splitting of a carbon–carbon bond between the first and second carbon atom in a 2-hydroxyacyl-CoA intermediate leading to the production of an (n−1) aldehyde and formyl-CoA. The latter is rapidly converted into formate and subsequently to CO2. HACL1 is a homotetramer and has a PTS (peroxisomal targeting signal) at the C-terminal side (PTS1). No deficiency of HACL1 has been described yet in human, but thiamin deficiency might affect its activity.

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