Biogenesis of intestinal lactase-phlorizin hydrolase in adults with lactose intolerance. Evidence for reduced biosynthesis and slowed-down maturation in enterocytes.
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.
Sterchi
E E
EE
Department of Gastroenterology, Children's Hospital, University of Berne, Switzerland.
Mills
P R
PR
Fransen
J A
JA
Hauri
H P
HP
Lentze
M J
MJ
Naim
H Y
HY
Ginsel
L
L
Bond
J
J
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
D008715:Methionine; D013394:Sucrase-Isomaltase Complex; D001616:beta-Galactosidase; D010694:Lactase-Phlorizin Hydrolase; D000626:Aminopeptidases; D018826:CD13 Antigens