LATE ONSET LACTASE DEFICIENCY: EVIDENCE OF ALTERATIONS IN THE POST-TRANSLATIONAL PROCESSING OF LACTASE

摘要

Twenty volunteers with late-onset clinical lactose-intolerance have been investigated. Mean lactase activity measured in small intestinal biopsy homogenates was 8.55 IU/g protein vs 27.4 IU/g protein in controls (31/2%), mean sucrase activity was 74.6 IU/g protein vs 46.1 IU/g protein in controls (161.8%). Maltase and Isomaltase activities were not significantly different. The ratio of total lactase-protein to aminopeptidase N-protein was reduced to 14.7% as assessed by analysis of iodinated and immunoprecipitated protein on SDS-PACE. Biosynthesis of lactase, sucrase and aminopeptidase N was studied in organ culture of small intestinal biopsies, followed by analysis of immunoisolated enzymes on SDS-PAGE. In biopsies from individuals with reduced lactase activity biosynthesis of lactase was reduced to (10%, while biosynthesis of sucrase was increased to 223%.) In addition, proteolytic processing of Pro-lactase to the mature enzyme was found to be occurring at a much lower rate. After 4 h of culture, 82% of total lactase was still present in the form of Pro-lactase in tissue from lactase-deficient individuals whereas in control tissue this was only 41%. Immuno-electron-microscopy wit protein A-gold-labelling revealed an accumulation of immuno-reactive staining in the Golgi region of enterocytes from lactase-deficient tissue with almost absent staining in the microvillus membrane.Conclusion: In late-onset lactase-deficiency, biosynthesis of lactase is reduced at the transcriptional or translational level, and in addition post-translational proteolytic processing is slowed down leading to an intracellular accumulation of lactase and probably to its subsequent intracellular degradation, thus preventing the synthesised molecules from reaching the microvillus membrane. An unexpected finding was the increased level of sucrase in tissue from lactase-deficient individuals. Possibily, this is an attempt by the enterocytes to compensate for the inability to hydrolyse lactose.