HUMAN GASTRIC LIPASE

Abstract

Ninety percentofthe dietary lipids in humans are triglycerides which constitute the essential part of the 100g to 150g daily fat intake in industrialized countries. It was thoughtuntil recently that the hydrolysis of dietary triglycerides began in the intestinal lumen and was catalysed exclusively by pancreatic lipase. Studies on gastrointestinal lipolysis have underestimated several importantpoints, particularly the role of gastric lipolysis. It is now well established that Human Gastric Lipase (HGL), is the first lipolytic enzyme involved in dietary fat digestion. HGL originates entirely from the fundic mucosa. Nolipolytic activity was detected in the lingual, pharyngeal or oesophagus areas. Using immunocytolocalization techniques, cells producing HGLwereidentified as the chief cells of gastric fundic glands already known to biosynthesize pepsin. HGL was purified to electrophoretic homogeneity (MW = 50 kDa)from gastric juice. It is a glycoprotein with a glycan moiety amounting about 15 to 20 % ofthe total protein weight. The complete amino acid sequence of HGL,derived from cDNA sequence, shows 80 % homology with rat lingual lipase. No structural homology exists between human gastric lipase and pancreatic lipase, except the G-X-S-X-G sequence found in otherlipases andserine esterases. This sequence containsa serine analogousto the essential Ser- 152 in human pancreatic lipase. HGL contains one free sulfhydryl group whichis essential to the expressionoflipaseactivity. HGL hydrolyses short chain (tributyrin) and long chain (Intralipide) triacylglycerols at similar rates. HGL activity is very dependentupon the interfacial tension between triacylglycerol and water. In the presence of amphiphiles such as bile salts or alimentary proteins, the tributyrin-waterinterfacial tension decreases and HGLis activated. Thus HGLis capable of hydrolyzing triglyceride emulsionsin the presence ofbile salts concentration prevailing in the upper small intestine and in the presence of alimentary proteins. These observations could explain the high dietary lipid absorption observed underpancreatic lipase deficiency. In vitro studies showed that prehydrolysis by HGLofIntralipide emulsion enable it to be subsequently hydrolyzed by humanpancreatic lipase. Fatty acid liberated by HGL probablytriggerthe later action of pancreatic lipase by changing the interfacial tension.