Phenylalanine ammonia-lyase and Histidine ammonia-lyase family enzymes (PAL/HAL family)

The Phenylalanine ammonia-lyase (PAL) and Histidine ammonia-lyase (HAL) family comprises enzymes that utilize a unique 4-methylidene-imidazole-5-one (MIO) cofactor to catalyze the non-oxidative deamination of aromatic amino acids [1, 4]. PAL is responsible for converting L-phenylalanine into trans-cinnamic acid and ammonia, a process primarily found in plants and bacteria but absent in mammals [2]. HAL, also known as histidase, is a human enzyme that converts L-histidine into urocanic acid, playing a vital role in histidine catabolism [1, 5]. Deficiencies in HAL lead to histidinemia, while PAL has been successfully adapted as a therapeutic enzyme for patients with Phenylketonuria (PKU) [3, 4]. The drug Pegvaliase is a PEGylated recombinant PAL that provides an alternative metabolic route to lower toxic phenylalanine levels in PKU patients who do not respond to other treatments [3]. However, the use of these non-human enzymes carries significant risks of immunogenicity and anaphylaxis, requiring careful patient monitoring and often a Risk Evaluation and Mitigation Strategy (REMS) [3]. Sources: [1] UniProt Consortium. Histidine ammonia-lyase (P42357). [2] National Center for Biotechnology Information (NCBI). Phenylalanine Ammonia-Lyase. [3] U.S. Food and Drug Administration (FDA). Palynziq (pegvaliase-pqpz) Prescribing Information. [4] Pilbak, S., et al. (2012). The MIO-dependent ammonia-lyase family. [5] Suchi, M., et al. (1995). Molecular cloning and characterization of the human histidine ammonia-lyase gene.

Other names

Aromatic amino acid lyasesMIO-dependent lyasesHistidasePhenylalanine ammonia-lyaseHistidine ammonia-lyasePALHAL

Enzyme substitution therapy to reduce systemic levels of phenylalanine by converting it to trans-cinnamic acid and ammonia.