ENPP7

Description

The ENPP7 (ectonucleotide pyrophosphatase/phosphodiesterase 7) is a protein-coding gene located on chromosome 17.

ENPP7, also known as Alkaline sphingomyelin phosphodiesterase (Alk-SMase) or Intestinal alkaline sphingomyelinase, is an enzyme encoded by the ENPP7 gene in humans. Its activity was initially identified in 1969 as a type of sphingomyelinase that breaks down sphingomyelin into ceramide in the intestinal tract. The enzyme was later purified and named alkaline sphingomyelinase (alk-SMase) due to its optimal pH of 9.0 and its primary substrate, sphingomyelin. While the name alk-SMase was commonly used, cloning studies revealed that it shares no structural similarities with acid or neutral SMase, but instead belongs to the family of ecto nucleotide pyrophosphatase/phosphodiesterase (ENPP). Therefore, it was renamed ENPP7 or NPP7. A 3D homology model of ENPP7 was recently built using the crystal structure of an NPP member in bacteria as a template. Unlike other ENPP members, ENPP7 appears to be expressed only in the intestinal mucosa in various species, with additional expression in the human liver. In the intestinal tract, ENPP7 activity is low in the duodenum and colon but high in the middle of the jejunum.

ENPP7 is a choline-specific phosphodiesterase that hydrolyzes sphingomyelin, releasing ceramide and phosphocholine. This activity plays a role in sphingomyelin digestion, ceramide formation, and fatty acid absorption in the gastrointestinal tract. ENPP7 also exhibits phospholipase C activity, cleaving phosphocholine from palmitoyl lyso-phosphatidylcholine and platelet-activating factor (PAF), leading to their inactivation. Notably, ENPP7 lacks nucleotide pyrophosphatase activity. It is suggested that ENPP7 may promote cholesterol absorption by influencing sphingomyelin levels derived from both dietary and endogenous sources within the intestinal lumen.

ENPP7 is also known as ALK-SMase, E-NPP 7, NPP-7, NPP7.

Associated Diseases

WES Whole Exome Sequencing