Pyridoxal 5'-phosphate (PLP) (PLP)

Pyridoxal 5'-phosphate (PLP) is the metabolically active form of Vitamin B6 and serves as an essential coenzyme for more than 140 distinct enzymatic reactions in human metabolism [1, 3]. It is primarily involved in amino acid metabolism, where it facilitates transamination, decarboxylation, and racemization reactions [1, 2]. PLP is a critical cofactor for the synthesis of key neurotransmitters including gamma-aminobutyric acid (GABA), serotonin, dopamine, and norepinephrine [1, 2]. Additionally, PLP plays a vital role in heme biosynthesis, glycogenolysis, and the conversion of tryptophan to niacin [3]. While PLP itself is a nutrient rather than a traditional protein drug target, it is pharmacologically significant because several medications, such as isoniazid and penicillamine, act as antagonists or deplete PLP levels [1, 4]. This depletion can lead to clinical deficiency symptoms, including peripheral neuropathy and seizures [1]. Conversely, therapeutic administration of PLP or its precursor, pyridoxine, is used to treat specific genetic disorders like pyridoxine-dependent epilepsy [1, 3]. It is also used to mitigate the side effects of drugs that interfere with B6 metabolism [3]. Monitoring PLP levels is essential in patients on long-term therapy with B6-antagonists to prevent neurotoxicity [1]. Overall, PLP is a fundamental metabolic component whose availability is a key factor in both health and drug-induced pathology [2, 3].

Other names

Vitamin B6PyridoxinePyridoxal phosphateP5PPyridoxaminePyridoxal

Acts as a coenzyme (prosthetic group) for enzymes by forming a Schiff base with the ε-amino group of a specific lysine residue, facilitating various chemical transformations of amino acid substrates [1, 2, 4].