Cystals and cross-linked enzyme crystals (CLEC)of fungal and bacterial lipases and correction of canine pancreatic steatorrhea

Abstract

Background: The exolipase of Burkholderia plantarii has a high specific activity and corrects canine pancreatic steatorrhea when dogs are fed a high fat diet (GE 1997;112:2048 & 1999;116:431). We hypothesized that crystals and CLECs of lipases from other organisms would exhibit a high specific activity (~5000 IV/mg vs ~30 IV/mg for porcine lipase) and correct pancreatic steatorrhea. Further, CLECs might stabilize lipase against inactivation by acid, proteolytic enzymes and by the presence of bile acids. Aims: To compare the effects of crystals and cross-linked lipases of Candida rugosa (CR) and Burkholderia cepacia (BC) with B. plantarii (BL) on fat absorption in dogs with exocrine pancreatic insufficiency. Methods: Four dogs underwent ligation of major and minor pancreatic ducts. The coefficient of fat absorption (CFA) was measured by 72-hr fecal balance studies before and after operation and 3 wk after operation with 300,000 IV of BL or 600,000 IV of lipolytic activity of CR and BC lipases. During these studies, dogs ingested a high fat diet (43% fat, 36% protein and 21% CHO as % of calories [1700 kCal/d)). ANOVA and post hoc t-tests with Bonferonni correction were used to determine if there were significant differences among treatments. Results: CFA was significantly different among treatments (ANOVA, p<O.OOOOI) and the CFA was significantly greater (p<0.05) compared to no treatment (control postop) when the dogs were given crystalline CR, crystalline BC, crosslinked BC or BL (table). Conclusions: Crystal forms of CR and PC and CLECs of BC are as effective as BL in reducing pancreatic steatorrhea and are candidate lipases for treating human pancreatic steatorrhea.