title: Perinatal hypophosphatasia: tissue levels of vitamin B6 are unremarkable despite markedly increased circulating concentrations of pyridoxal-5'-phosphate. Evidence for an ectoenzyme role for tissue-nonspecific alkaline phosphatase.
abstract: "Perinatal" hypophosphatasia is the most severe form of this inborn error of metabolism, which is characterized by deficient activity of the tissue-nonspecific (liver/bone/kidney) isoenzyme of alkaline phosphatase (ALP) (TNSALP). We report that autopsy tissue from three affected subjects, which was profoundly low in ALP activity, had essentially unremarkable levels of pyridoxal-5'-phosphate (PLP), pyridoxal, and total vitamin B6 content despite markedly elevated plasma PLP levels (5,800, 14,500, and 98,500 nM; adult norm, 5-109 nM). Our findings help to explain the general absence of symptoms of vitamin B6 excess or deficiency in hypophosphatasia, and provide evidence that TNSALP acts as an ectoenzyme to regulate extracellular rather than intracellular concentrations of PLP (the cofactor form of vitamin B6) and perhaps other phosphate compounds.
authors.affiliation: Metabolic Research Unit, Shriners Hospital for Crippled Children, St. Louis, Missouri 63131.
authors.forename: M P
authors.initials: MP
authors.lastname: Whyte
authors.forename: J D
authors.initials: JD
authors.lastname: Mahuren
authors.forename: K N
authors.initials: KN
authors.lastname: Fedde
authors.forename: F S
authors.initials: FS
authors.lastname: Cole
authors.forename: E R
authors.initials: ER
authors.lastname: McCabe
authors.forename: S P
authors.initials: SP
authors.lastname: Coburn
mesh_terms: D000469:Alkaline Phosphatase / Q000172:deficiency* / Q000502:physiology; D005260:Female; D005313:Fetal Death; D006801:Humans; D007014:Hypophosphatasia / Q000378:metabolism*; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011730:Pyridoxal / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000097:blood*; D011736:Pyridoxine / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D011730:Pyridoxal; D011732:Pyridoxal Phosphate; D000469:Alkaline Phosphatase; D011736:Pyridoxine