Mammalian 2-hydroxyacyl-CoA lyases: Discovery and assays

2-Hydroxyacyl-CoA-lyases (HACLs) catalyze a carbon-carbon cleavage of long chain 2-hydroxyacyl-CoAs, generating formyl-CoA and a one-carbon shortened long chain aldehyde as primary products. Two enzymes were characterized in mammals, one being a peroxisomal matrix enzyme (HACL1), the other associated with the endoplasmic reticulum (HACL2). They are the sole known thiamine pyrophosphate depending enzymes involved in the breakdown of fatty acids, and are crucial for the α-oxidation of phytanic acid and long chain 2-hydroxy fatty acids.