Phenylalanine ammonia-lyase (PAL) (PAL)

Phenylalanine ammonia-lyase (PAL) is a non-human enzyme, predominantly found in plants and microorganisms, that catalyzes the conversion of the amino acid L-phenylalanine into trans-cinnamic acid and ammonia. Although not naturally occurring in the human genome, PAL is a critical therapeutic molecule for the treatment of Phenylketonuria (PKU), an autosomal recessive disorder where patients cannot metabolize phenylalanine due to a deficiency in the endogenous enzyme phenylalanine hydroxylase. By acting as an enzyme substitution therapy, recombinant versions of PAL lower systemic phenylalanine levels, preventing the neurotoxic effects and cognitive impairment associated with the disease. The primary clinical example is Pegvaliase (Palynziq), a PEGylated recombinant PAL derived from the cyanobacterium Anabaena variabilis. Beyond its use in PKU, PAL is explored for its potential in treating other metabolic disorders such as tyrosinemia and as a therapeutic strategy for auxotrophic cancers that rely on exogenous phenylalanine for growth. However, the use of PAL as a biopharmaceutical is challenged by its high immunogenicity, requiring chemical modifications such as PEGylation and close monitoring for potential anaphylactic reactions.

Other names

Ammonia-lyasePhenylalanine ammonia lyaseL-phenylalanine ammonia-lyasePhe ammonia-lyaseEC 4.3.1.24

The enzyme catalyzes the non-oxidative deamination of L-phenylalanine to produce trans-cinnamic acid and ammonia, thereby reducing toxic systemic phenylalanine concentrations in patients with metabolic deficiencies.