Aromatic-amino-acid transaminase (ArAT) (ArAT)

Aromatic-amino-acid transaminase (ArAT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that plays a central role in the metabolism of aromatic amino acids, including phenylalanine, tyrosine, and tryptophan [Source: BRENDA, EC 2.6.1.57]. It catalyzes the reversible transfer of an amino group from these substrates to an alpha-keto acid acceptor, such as 2-oxoglutarate or pyruvate, to form corresponding arylpyruvates [Source: Wikipedia]. In humans, this activity is primarily associated with kynurenine aminotransferases (KATs), which produce kynurenic acid, a neuroprotective metabolite linked to the pathophysiology of schizophrenia and Alzheimer's disease [Source: PMC3057211]. Recently, ArAT has gained attention as a therapeutic target in the gut microbiome, where bacterial enzymes from species like Clostridium sporogenes degrade L-DOPA, thereby reducing its efficacy in treating Parkinson's disease [Source: ResearchGate]. Additionally, ArAT is essential for the growth of opportunistic pathogens like Candida glabrata, making it a potential target for novel antifungal therapies [Source: ASM Journals]. Inhibition of this enzyme, while promising for modulating neurotransmitter levels or drug bioavailability, requires high specificity to avoid interfering with essential host metabolic processes and other transaminases [Source: J. Med. Chem.].

Other names

Aromatic amino acid aminotransferaseAromatic aminotransferaseTyrosine (aromatic) aminotransferasePhenylalanine aminotransferaseAAAATKynurenine aminotransferaseAro8TyrB

Drugs targeting aromatic-amino-acid transaminase typically act as competitive inhibitors that bind to the active site, often mimicking the substrate's structure or covalently binding to the pyridoxal 5'-phosphate (PLP) cofactor to prevent the transamination reaction [Source: J. Med. Chem., ASM Journals].