Sucrase-isomaltase Deficiency in Humans. Different Mutations Disrupt Intracellular Transport, Processing, and Function of an Intestinal Brush Border Enzyme

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1988 Aug 1

PMID 3403721

Citations 24

Authors

H Y Naim

J Roth

E E Sterchi

M Lentze

P Milla

J Schmitz

H P Hauri

Affiliations

Soon will be listed here.

Abstract

Eight cases of congenital sucrase-isomaltase deficiency were studied at the subcellular and protein level with monoclonal antibodies against sucrase-isomaltase. At least three phenotypes were revealed: one in which sucrase-isomaltase protein accumulated intracellularly probably in the endoplasmic reticulum, as a membrane-associated high-mannose precursor, one in which the intracellular transport of the enzyme was apparently blocked in the Golgi apparatus, and one in which catalytically altered enzyme was transported to the cell surface. All patients expressed electrophoretically normal or near normal high-mannose sucrase-isomaltase. The results suggest that different, probably small, mutations in the sucrase-isomaltase gene lead to the synthesis of transport-incompetent or functionally altered enzyme which results in congenital sucrose intolerance.

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References

Dahlqvist A . Assay of intestinal disaccharidases. Anal Biochem. 1968; 22(1):99-107. DOI: 10.1016/0003-2697(68)90263-7. View

Garen A, Levinthal C . A fine-structure genetic and chemical study of the enzyme alkaline phosphatase of E. coli. I. Purification and characterization of alkaline phosphatase. Biochim Biophys Acta. 1960; 38:470-83. DOI: 10.1016/0006-3002(60)91282-8. View

Dubs R, Steinmann B, GITZELMANN R . Demonstration of an inactive enzyme antigen in sucrase-isomaltase deficiency. Helv Paediatr Acta. 1973; 28(3):187-98. View

Kelly J, Alpers D . Blood group antigenicity of purified human intestinal disaccharidases. J Biol Chem. 1973; 248(23):8216-21. View

PREISER H, Menard D, CRANE R, Cerda J . Deletion of enzyme protein from the brush border membrane in sucrase-isomaltase deficiency. Biochim Biophys Acta. 1974; 363(2):279-82. DOI: 10.1016/0005-2736(74)90067-4. View

Palade G . Intracellular aspects of the process of protein synthesis. Science. 1975; 189(4200):347-58. DOI: 10.1126/science.1096303. View

Schmitz J, Commegrain C, Maestracci D, Rey J . Absence of brush border sucrase-isomaltase complex in congenital sucrose intolerance. Biomedicine. 1974; 21(11):440-3. View

Gray G, Conklin K, TOWNLEY R . Sucrase-isomaltase deficiency. Absence of an inactive enzyme variant. N Engl J Med. 1976; 294(14):750-3. DOI: 10.1056/NEJM197604012941403. View

Freiburghaus A, Dubs R, HADORN B, Gaze H, Hauri H, GITZELMANN R . The brush border membrane in hereditary sucrase-isomaltase deficiency: abnormal protein pattern and presence of immunoreactive enzyme. Eur J Clin Invest. 1977; 7(5):455-9. DOI: 10.1111/j.1365-2362.1977.tb01634.x. View

10.

Hercz A, Katona E, Cutz E, Wilson J, Barton M . alpha1-Antitrypsin: the presence of excess mannose in the Z variant isolated from liver. Science. 1978; 201(4362):1229-32. DOI: 10.1126/science.308696. View

11.

FRANK G, Brunner J, Hauser H, WACKER H, Semenza G, Zuber H . The hydrophobic anchor of small-intestinal sucrase--isomaltase: N-terminal sequence of isomaltase subunit. FEBS Lett. 1978; 96(1):183-8. DOI: 10.1016/0014-5793(78)81090-4. View

12.

Hauri H, Quaroni A, Isselbacher K . Biogenesis of intestinal plasma membrane: posttranslational route and cleavage of sucrase-isomaltase. Proc Natl Acad Sci U S A. 1979; 76(10):5183-6. PMC: 413104. DOI: 10.1073/pnas.76.10.5183. View

13.

Kobata A . Use of endo- and exoglycosidases for structural studies of glycoconjugates. Anal Biochem. 1979; 100(1):1-14. DOI: 10.1016/0003-2697(79)90102-7. View

14.

Sjostrom H, Noren O, Christiansen L, WACKER H, Semenza G . A fully active, two-active-site, single-chain sucrase.isomaltase from pig small intestine. Implications for the biosynthesis of a mammalian integral stalked membrane protein. J Biol Chem. 1980; 255(23):11332-8. View

15.

Hauri H, Quaroni A, Isselbacher K . Monoclonal antibodies to sucrase/isomaltase: probes for the study of postnatal development and biogenesis of the intestinal microvillus membrane. Proc Natl Acad Sci U S A. 1980; 77(11):6629-33. PMC: 350340. DOI: 10.1073/pnas.77.11.6629. View

16.

Skovbjerg H, Krasilnikoff P . Immunoelectrophoretic studies on human small intestinal brush border proteins. The residual isomaltase in sucrose intolerant patients. Pediatr Res. 1981; 15(3):214-8. DOI: 10.1203/00006450-198103000-00004. View

17.

Owen M, Kissonerghis A, Lodish H, Crumpton M . Biosynthesis and maturation of HLA-DR antigens in vivo. J Biol Chem. 1981; 256(17):8987-93. View

18.

Farquhar M, Palade G . The Golgi apparatus (complex)-(1954-1981)-from artifact to center stage. J Cell Biol. 1981; 91(3 Pt 2):77s-103s. PMC: 2112780. DOI: 10.1083/jcb.91.3.77s. View

19.

HERSCOVICS A, Quaroni A, Bugge B, Kirsch K . Partial characterization of the carbohydrate units of rat intestinal sucrase--isomaltase. Biochem J. 1981; 197(2):511-4. PMC: 1163153. DOI: 10.1042/bj1970511. View

20.

Sabatini D, Kreibich G, Morimoto T, Adesnik M . Mechanisms for the incorporation of proteins in membranes and organelles. J Cell Biol. 1982; 92(1):1-22. PMC: 2112015. DOI: 10.1083/jcb.92.1.1. View