General Information:

Id: 9,380 (click here to show other Interactions for entry)
Diseases: Hypophosphatasia, adult - [OMIM]
Mammalia
review
Reference: Orimo H(2016) Pathophysiology of hypophosphatasia and the potential role of asfotase alfa Ther Clin Risk Manag 12: 777-786 [PMID: 27274262]

Interaction Information:

Comment A physiological role of TNAP is associated with neurotransmitter synthesis in the central nervous system. One of the physiological substrates of TNAP is pyridoxal 5'-phosphate, a derivative of vitamin B6, which is necessary for the biosynthesis of GABA, a cofactor of glutamic acid carboxylase in neuronal cells. GABA is known to act as a repressive neurotransmitter. For pyridoxal 5'-phosphate entry into cells, the phosphate moiety has to be first released, and then pyridoxal is incorporated into the cells, followed by rephosphorylation within the cells. It has been confirmed in fibroblasts from normal and HPP patients that TNAP hydrolyzes pyridoxal 5'-phosphate to release phosphate outside the cell membrane, and therefore a similar mechanism is presumed to operate in the neuronal cell membrane. Failure of this role of TNAP leads to epileptic seizures in HPP patients because reduced GABA in the neuronal cells results in hyperactivity of the central nervous system.
Formal Description
Interaction-ID: 102025

gene/protein

ALPL

affects_quantity of

drug/chemical compound

GABA