Pyridoxal 5'-phosphate-dependent decarboxylase (PLP-dependent decarboxylase)

Pyridoxal 5'-phosphate (PLP)-dependent decarboxylases are a diverse family of enzymes that utilize the active form of Vitamin B6 as an essential cofactor to catalyze the removal of a carboxyl group from amino acid substrates [1]. These enzymes play a fundamental role in human physiology by facilitating the biosynthesis of critical biogenic amines and neurotransmitters, including dopamine, serotonin, histamine, and gamma-aminobutyric acid (GABA) [2]. For instance, DOPA decarboxylase (Aromatic L-amino acid decarboxylase) is vital for catecholamine production, while glutamate decarboxylase is responsible for synthesizing the primary inhibitory neurotransmitter GABA [3]. In clinical practice, these enzymes are significant therapeutic targets; inhibitors such as carbidopa and benserazide are co-administered with levodopa to treat Parkinson's disease by preventing the peripheral metabolism of the drug [4]. Furthermore, ornithine decarboxylase is a key target in oncology and the treatment of African trypanosomiasis due to its rate-limiting role in polyamine synthesis, which is essential for cell proliferation [5]. Because PLP is involved in over 140 different enzymatic reactions, drugs targeting these decarboxylases must be carefully designed to avoid systemic Vitamin B6 depletion or unintended interference with other metabolic pathways [1]. [1] Toney, M. D. (2005). Archives of Biochemistry and Biophysics. [2] Eliot, A. C., & Kirsch, J. F. (2004). Annual Review of Biochemistry. [3] Buddhala, C., et al. (2009). Journal of Biological Chemistry. [4] StatPearls (2023). Carbidopa. [5] Casero, R. A., & Marton, L. J. (2007). Nature Reviews Drug Discovery.

Other names

Vitamin B6-dependent decarboxylaseAmino acid decarboxylasePLP-decarboxylaseGroup II decarboxylase

Inhibition of the decarboxylation of amino acids by forming a Schiff base with the PLP cofactor or covalently binding to the enzyme active site, thereby preventing the formation of biogenic amines.