Inorganic Pyrophosphate, a Potent Inhibitor of Mineralization, is a Natural Substrate of Alkaline Phosphatase.
The TNSALP The biological unit of heredity that is made up of a DNA sequence, occupies a precise location (locus) on a chromosome, and contains instructions for the production of a particular protein.gene expresses tissue non-specific alkaline phosphatase (TNSALP) especially in bone and liver.
Genetic mutation that results in a protein with little or no function.Loss-of-function mutations in this gene result in deficiency of TNSALP. TNSALP is an An enzyme that works outside of the cell that secretes it.ectoenzyme tethered to the outer surface of osteoblast and chondrocyte cell membranes (see figure). TNSALP hydrolyzes several substrates, including Regulates certain intracellular functions and extracellular crystal formation.inorganic pyrophosphate (PPi) and The active form of vitamin B6.pyridoxal 5’-phosphate (PLP) a major form of vitamin B6.
In a TSNALP deficient environment, inorganic pyrophosphate (PPi) accumulates extracellularly and potently inhibits formation of hydroxyapatite (mineralization) causing A softening of bones in children leading to fractures and deformity, which is predominantly caused by a vitamin D deficiency.rickets in infants and children and The adult form of rickets, which is a softening of the bones caused by defective bone mineralization.osteomalacia in adults. PLP is the principal form of vitamin B6 and must be The removal of a phosphate group to a protein or other organic molecule.dephosphorylated by TNSALP for PL to cross over the cell membrane and blood brain barrier. PLP accumulation causes PL deficiency and impaired synthesis of neurotransmitters, which can cause vitamin B6 responsive seizures. In some cases, deposition of calcium pyrophosphate dehydrate (CPPD) crystals in the joint can cause Clinically evident acute inflammation of synovial joints that resembles gouty arthritis.pseudogout .
Pathophysiology of A rare, inherited, and sometimes fatal metabolic bone disease characterized by poor bone mineralization and profound skeletal defects.Hypophosphatasia
(Courtesy of McKee, 2009)
