Alkaline sphingomyelinase (NPP7) in hepatobiliary diseases: A field that needs to be closely studied

Figure 1 Metabolism of sphingomyelin in the liver and potential implications of alk-SMase in liver diseases. Liver alk-SMase is localized on the hepatocyte canaliculi membrane. It hydrolyzes SM, PAF, and lyso-PC, resulting in increased ceramide (Cer) and decreased PAF and LPA, thus having anticancer and anti-inflammatory effects. Together with PC, cholesterol, and bile salts, SM is released in canaliculi and transported to gallbladder, where the interactions of these compounds affect gallstone formation. When the bile is delivered into the intestinal tract, bile salt will release additional alk-SMase from intestinal mucosa, and digest intestinal SM to ceramide and phosphocholine (Pch). Meanwhile, PC will be hydrolyzed by enzymes from pancreas and intestinal mucosa to choline compounds such as free choline, lyso-PC, and Pch. These choline compounds will be transported to liver where to be used for synthesis of PC. Pch moiety in PC can be transferred to ceramide to form SM by SM synthases. Part of the SM formed will be released into blood together with lipoproteins, part to bile, and part to be degraded by alk-SMase and acid SMase (ASMase) in the liver.