The generation of lysolecithin by enterokinase in trypsinogen prophospholipase A2 lecithin mixtures, and its relevance to the pathogenesis of acute necrotising pancreatitis.
The cascade enterokinase-trypsinogen-prophospholipase A2 lecithin, generating trypsin, phospholipase A2 and lysolecithin, respectively, was studied in vitro using a novel phospholipase A2 assay. The rate of enterokinase catalysed activation of trypsinogen was maximal at 4 mmol/1 glycodeoxycholic acid; higher concentrations of bile salt progressively inhibited enterokinase activity. Net phospholipase A2 activity in reaction mixtures was critically dependent on the trypsin/prophospholipase A2 molar ratio. Lecithin hydrolysis by phospholipase A2 was dependent on the bile salt/lecithin molar ratio and was optimal at 1.25 to 1. The addition of enterokinase to lecithin and bile salt mixtures, containing trypsinogen and prophospholipase A2 at presumed pathophysiological concentrations, resulted in the generation of concentrations of lysolecithin lytic for pancreatic acinar cells within 5 min. These findings would support the concept that the entry of bile containing active enterokinase into the pancreatic duct system in vivo may in some cases be involved in the initiation of necrotising acute pancreatitis in man.
D000208:Acute Disease; D010450:Endopeptidases / Q000378:metabolism*; D004765:Enteropeptidase / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006002:Glycodeoxycholic Acid / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000096:biosynthesis*; D009336:Necrosis; D010195:Pancreatitis / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism*
D004792:Enzyme Precursors; D008244:Lysophosphatidylcholines; D006002:Glycodeoxycholic Acid; D014362:Trypsinogen; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010450:Endopeptidases; D014357:Trypsin; D004765:Enteropeptidase