title: Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down maturation in enterocytes.
abstract: Enzymatic activity, biosynthesis, and maturation of lactasephlorizin hydrolase (LPH) were investigated in adult volunteers with suspected lactose intolerance. Mean LPH activity in jejunal biopsy homogenates of these individuals was 31% compared to LPH-persistent individuals, and was accompanied by a reduced level of LPH-protein. Mean sucrase activity in individuals with low LPH was increased to 162% and was accompanied by an increase in sucrase-isomaltase (SI)-protein. Biosynthesis of LPH, SI, and aminopeptidase N (APN) was studied in organ culture of small intestinal biopsy specimens. In individuals with LPH restriction, the rate of synthesis of LPH was drastically decreased, reaching just 6% of the LPH-persistent group after 20 h of culture, while the rate of synthesis of SI appeared to be increased. In addition, maturation of pro-LPH to mature LPH occurred at a slower rate in LPH-restricted tissue. Immunoelectron microscopy revealed an accumulation of immunoreactive LPH in the Golgi region of enterocytes from LPH-restricted individuals and reduced labeling of microvillus membranes. Therefore, lactose intolerance in adults is mainly due to a decreased biosynthesis of LPH, either at the transcriptional or translational level. In addition, intracellular transport and maturation is retarded in some of the LPH-restricted individuals, and this leads to an accumulation of newly synthesized LPH in the Golgi and a failure of LPH to reach the microvillus membrane.
authors.affiliation: Department of Gastroenterology, Children's Hospital, University of Berne, Switzerland.
authors.forename: E E
authors.initials: EE
authors.lastname: Sterchi
authors.forename: P R
authors.initials: PR
authors.lastname: Mills
authors.forename: J A
authors.initials: JA
authors.lastname: Fransen
authors.forename: H P
authors.initials: HP
authors.lastname: Hauri
authors.forename: M J
authors.initials: MJ
authors.lastname: Lentze
authors.forename: H Y
authors.initials: HY
authors.lastname: Naim
authors.forename: L
authors.initials: L
authors.lastname: Ginsel
authors.forename: J
authors.initials: J
authors.lastname: Bond
mesh_terms: D000328:Adult; D000626:Aminopeptidases / Q000096:biosynthesis; D018826:CD13 Antigens; D006801:Humans; D007422:Intestines / Q000201:enzymology*; D010694:Lactase-Phlorizin Hydrolase / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D007787:Lactose Intolerance / Q000201:enzymology*; D008715:Methionine / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology; D013394:Sucrase-Isomaltase Complex / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D008715:Methionine; D013394:Sucrase-Isomaltase Complex; D001616:beta-Galactosidase; D010694:Lactase-Phlorizin Hydrolase; D000626:Aminopeptidases; D018826:CD13 Antigens