Kinetic mechanism of ENPP1 ATPase: Implications for aberrant calcification disorders and enzyme replacement therapy.

Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is a transmembrane glycoprotein enzyme with an extracellular catalytic domain that hydrolyzes ATP into AMP and pyrophosphate (PP). The ENPP1 ATPase is the major source of extracellular PP, a critical physiological regulator of calcium phosphate crystal formation and biomineralization. ENPP1 deficiency lowers systemic PP levels and induces life-threatening arterial calcifications.

Improvements in hearing loss with bone-targeted enzyme replacement therapy are associated with corrected hypomineralization and osteocyte properties of auditory ossicles in Enpp1-deficient mice.

Hearing loss is common in conditions caused by ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency, such as generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2. Mechanistically, it is hypothesized that poor mineralization of the auditory ossicles leads to impaired sound transmission in the middle ear. Here we investigated whether enzyme replacement therapy (ERT) improves hearing loss in an Enpp1-deficient mouse model and whether this is associated with corrected bone properties in the ossicles.

Bromophosphatation as a Mode of Chiral Phosphoric Acid Catalyst Deactivation as Elucidated by Kinetic Profiling.

A BINOL-derived chiral phosphoric acid ()- was shown by kinetic profiling to be deactivated during the catalytic bromoesterification of cyclohexene. The products of the deactivation were identified as diastereoisomeric phosphates (,1,2)- and (,1,2)- and are formed via an alkene bromophosphatation process where the phosphate of behaves as a competitive nucleophile, as confirmed by authentic preparations of and from a stoichiometric bromophosphatation reaction. HPLC separation of the diastereoisomers gave pure whose absolute and relative configurations were proven by single-crystal X-ray diffraction.

Structure confirmation, reactivity, bacterial mutagenicity and quantification of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in drinking water.

The presence of two new disinfectant by-product (DBP) groups in the UK was recently shown using non-target analysis, halogenated-hydroxycyclopentenediones and halogenated-methanesulfonic acids. In this work, we confirmed the structure of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione (TBHCD), and quantified it together with dibromomethanesulfonic acid at 122 ± 34 and 326 ± 157 ng L on average in London's drinking water, respectively (n = 21). We found TBHCD to be photolabile and unstable in tap water and at alkaline pH.

Effect of Mutation Type on Ectopic Ossification Among Adult Patients With X-Linked Hypophosphatemia.

Context: Causative factors for ectopic ossifications in X-linked hypophosphatemia (XLH) remain to be elucidated.

Objective: This work aimed to investigate the genotype-phenotype correlations between the phosphate-regulating endopeptidase homologue, X-linked gene () and ectopic ossifications in XLH.

Methods: Biochemical data, spinal computed tomography scans, and x-rays of hip/knee joints were retrospectively reviewed.