Pyridoxal-5-Phosphate

Pyridoxal-5-phosphate is the coenzyme, or active, form of vitamin B6, with the chemical formula C8H10NO6P ^[1]. Vitamin B6 is not a single substance but a group of closely related molecules, called vitamers, that include pyridoxine, pyridoxal, and pyridoxamine along with their phosphorylated versions ^[1][2]. Whichever form is eaten, the body converts it through a series of enzyme steps into PLP; pyridoxal is phosphorylated by the enzyme pyridoxal kinase, and an oxidase enzyme completes the conversion of other vitamers to the active coenzyme ^[1]. Because humans cannot make the vitamin from scratch, vitamin B6 must come from the diet ^[1].

PLP is one of the most versatile cofactors in biochemistry, taking part in well over a hundred distinct enzyme-catalysed reactions, a large share of all known enzyme activities ^[1][2]. Most of these are steps in amino acid metabolism, such as transamination, decarboxylation, and deamination, and PLP-dependent enzymes are essential for building and breaking down amino acids and for interconverting them ^[1][2]. The coenzyme is central to the synthesis of several neurotransmitters, including serotonin, dopamine, and gamma-aminobutyric acid, and it also contributes to the first step of heme production, the breakdown of stored glycogen, the metabolism of tryptophan, and one-carbon and lipid metabolism ^[1][2][4]. Through these roles it touches nervous system function, the immune system, and the formation of red blood cells ^[1].

Because PLP underpins so many pathways, a shortage of vitamin B6 can produce wide-ranging problems, including skin inflammation, anemia, nerve damage, and, particularly in infants, seizures ^[1]. Certain rare inherited disorders bear directly on PLP. In some genetic epilepsies the enzyme that generates PLP is faulty, and affected newborns have seizures that respond to treatment with the vitamin given in an appropriate form ^[1]. In aromatic L-amino acid decarboxylase deficiency, a PLP-dependent enzyme needed to make dopamine and serotonin does not work properly, causing a severe neurological disorder from early life ^[4]. Interest in the coenzyme also extends to its behaviour as an antioxidant and to associations, still being studied, between low vitamin B6 and conditions such as cardiovascular disease, diabetes, and cancer ^[1].

Vitamin B6 is available as a supplement in several forms, most commonly pyridoxine, and also directly as pyridoxal-5-phosphate, which is promoted as a form that is already in the active coenzyme state and so does not require the body's conversion step ^[1]. PLP occurs naturally in many foods and is added to some fortified products and multivitamins, and it is generally regulated as a nutrient and dietary supplement ingredient rather than as a drug ^[1]. It is worth noting that very high intakes of vitamin B6 over long periods have been linked to reversible sensory nerve problems, so the vitamin is not without an upper limit despite being water-soluble ^[1].

Safe at sensible doses. The key caution is that chronically high-dose B6 (typically well above 100 mg/day for long periods) can cause peripheral neuropathy, which is usually reversible on stopping. Stick near the recommended range unless directed otherwise. Otherwise very well tolerated.