Revisiting vitamin B6 metabolism: The emerging role of pyridoxal reductase in the pyridoxal 5'-phosphate salvage pathway

Pyridoxal 5'-phosphate (PLP) is an essential enzyme cofactor in hundreds of metabolic reactions. While the classical PLP salvage pathway involves phosphorylation and oxidation steps, the reaction catalysed by pyridoxal reductase represents a pivotal and yet incompletely understood player. Identified across bacteria, plants and animals, this enzyme converts pyridoxal to pyridoxine, shaping PLP recycling and preventing toxic intermediate accumulation. In humans, AKR1C isozymes exhibit dual reductase and dehydrogenase activities, potentially linking vitamin B6 homeostasis with steroid metabolism. These findings suggest a regulatory network integrating biosynthesis, recycling and degradation, although mechanistic details and physiological roles remain unresolved and require further investigation.