Inborn errors affecting vitamin B6 metabolism

Vitamin B 6 is an important vitamin for normal brain function. The metabolism of dietary vitamin B 6 to its active cofactor pyridoxal 5´-phosphate is described. The mechanism of action of pyridoxal 5´-phosphate is described, as are some important functions in the brain. The clinical features and biochemistry of three inborn errors of metabolism affecting brain pyridoxal 5´-phosphate concentrations are described, each of which cause early-onset epilepsy of variable severity. These are pyridoxine phosphate oxidase deficiency, hyperprolinemia Type 2 and pyridoxine-dependent epilepsy caused by antiquitin deficiency. Hypophosphatasia is also discussed briefly, as the epilepsy that can complicate this disorder appears to be due to pyridoxal phosphate deficiency. Lastly, the antiepileptic properties of pyridoxine and pyridoxal phosphate are discussed. Vitamin B 6 is important for normal brain function , particularly in the immature brain [1]. Vitamin B 6 deficiency causes seizures and, if untreated, can lead to permanent neurological sequelae. This review describes the transport and metabolism of vitamin B 6 and the role of alkaline phosphatases. The clinical features and pathogenesis of three inborn errors of metabolism that cause deficiency of the active cofactor pyridoxal 5´-phosphate are also discussed (Table 1). Vitamin B 6 metabolism Vitamin B 6 is a water-soluble vitamin that is present in the body as six vitamers: pyridoxine (pyridoxol), pyridoxamine, pyridoxal and their 5´-phosphorylated esters. Only pyridoxal phosphate has cofactor activity. Vitamin B 6 is ingested from the diet and is present in many foods including meats, pulses, cereals, vegetables and some fruit; a proportion is also derived from intestinal bacterial flora. Animal-derived vitamin B 6 consists mostly of phosphorylated pyridoxal and pyridoxamine, whilst that from plants consists largely of free and bound pyridoxine [1]. Phosphorylated B 6 vitamers are converted to their free bases by intestinal alkaline phosphatases and these are then absorbed from the upper small intestine by a carrier-mediated system [2]. Absorption is rapid and the vitamers pass into the portal blood and are taken up by the liver. Here, pyri-doxine, pyridoxamine and pyridoxal are phos-phorylated by pyridoxal kinase to their 5´-phosphate esters and pyridoxine phosphate and pyridoxamine phosphate oxidized by pyridox(am)ine phosphate oxidase to form pyridoxal phosphate. Pyridoxal phosphate is released from the liver into the circulation where it is bound by albumin and forms approximately 60% of circulating vitamin B 6 with lesser amounts of pyridoxine, pyridoxamine and pyridoxal (Figure 1). Only the free vitamin bases can cross the blood–brain barrier, …