Vitamin B6-dependent decarboxylases and related enzymes (PLP-dependent enzymes)

Vitamin B6-dependent decarboxylases and related enzymes are a diverse group of proteins that utilize pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, as an essential cofactor to catalyze critical biochemical reactions, primarily the decarboxylation of amino acids [1.1.2, 1.2.3]. These enzymes are fundamental to the central nervous system, where they facilitate the biosynthesis of key neurotransmitters such as dopamine, serotonin, histamine, and gamma-aminobutyric acid (GABA) [1.1.3, 1.3.1]. Prominent members of this family include aromatic L-amino acid decarboxylase (AADC), glutamate decarboxylase (GAD), and ornithine decarboxylase (ODC) [1.2.1, 1.3.1]. Due to their central role in physiological processes, these enzymes are significant therapeutic targets; for instance, AADC inhibitors like carbidopa are used in Parkinson's disease to prevent peripheral degradation of levodopa, while ODC inhibitors like eflornithine are used in treating cancer and African trypanosomiasis [1.2.1, 1.3.2]. Dysregulation or genetic deficiencies in these enzymes are linked to various disorders, including pyridoxine-dependent epilepsy, movement disorders, and metabolic diseases [1.1.3, 1.4.2]. Therapeutic interventions often involve either the inhibition of these enzymes to modulate metabolite levels or the administration of vitamin B6 supplements to restore enzymatic activity in deficiency states [1.4.1, 1.4.4].

Other names

Pyridoxal phosphate-dependent enzymesB6-dependent enzymesPLP-dependent decarboxylasesGroup II decarboxylasesPLP-dependent amino acid decarboxylases

Drugs targeting these enzymes typically act as competitive or irreversible inhibitors to modulate neurotransmitter levels or cell growth, or serve as cofactor supplements to restore enzymatic function in deficiency states [1.2.1, 1.3.2, 1.4.1].