{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:30:13Z","timestamp":1793914213176,"version":"4.8.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>\n                    The two major intestinal \u03b1-glycosidases, sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM), are active towards \u03b1-1,4 glycosidic linkages that prevail in starch. These enzymes share striking structural similarities and follow similar biosynthetic pathways. It has been hypothesized that starch digestion can be modulated\n                    <jats:italic>via<\/jats:italic>\n                    \u201ctoggling\u201d of activities of these mucosal \u03b1-glycosidases, suggesting a possible interaction between these two enzyme complexes in the intestinal brush border membrane (BBM). Here, the potential interaction between SI and MGAM was investigated in solubilized BBMs utilizing reciprocal pull down assays, i.e., immunoprecipitation with anti-SI antibody followed by Western blotting with anti-MGAM antibody and\n                    <jats:italic>vice versa<\/jats:italic>\n                    . Our results demonstrate that SI interacts avidly with MGAM concomitant with a hetero-complex assembly in the BBMs. This interaction is resistant to detergents, such as Triton X-100 or Triton X-100 in combination with sodium deoxycholate. By contrast, inclusion of sodium deoxycholate into the solubilization buffer reduces the enzymatic activities towards sucrose and maltose substantially, most likely due to alterations in the quaternary structure of either enzyme. In view of their interaction, SI and MGAM regulate the final steps in starch digestion in the intestine, whereby SI assumes the major role by virtue of its predominant expression in the intestinal BBMs, while MGAM acts in auxiliary supportive fashion. These findings will help understand the pathophysiology of carbohydrate malabsorption in functional gastrointestinal disorders, particularly in irritable bowel syndrome, in which gene variants of SI are implicated.\n                  <\/jats:p>","DOI":"10.3389\/fmolb.2023.1160860","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:39Z","timestamp":1678233639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Interaction between the \u03b1-glucosidases, sucrase-isomaltase and maltase-glucoamylase, in human intestinal brush border membranes and its potential impact on disaccharide digestion"],"prefix":"10.3389","volume":"10","author":[{"given":"Stephanie","family":"Tannous","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Stellbrinck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Hoter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan Y.","family":"Naim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S0960-9822(99)80263-2\/ATTACHMENT\/3B87379F-D8CC-4538-A9C3-AB85C20A8132\/MMC1.PDF","article-title":"O-linked glycans mediate apical sorting of human intestinal sucrase-isomaltase through association with lipid rafts","volume":"9","author":"Alfalah","year":"1999","journal-title":"Curr. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1053\/J.GASTRO.2008.11.038","article-title":"Compound heterozygous mutations affect protein folding and function in patients with congenital sucrase-isomaltase deficiency","volume":"136","author":"Alfalah","year":"2009","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.3390\/NU9101106","article-title":"Characterization of mucosal disaccharidases from human intestine","volume":"9","author":"Amiri","year":"2017","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1016\/j.febslet.2007.04.035","article-title":"Evidence of native starch degradation with human small intestinal maltase-glucoamylase (recombinant)","volume":"581","author":"Ao","year":"2007","journal-title":"FEBS Lett."},{"key":"B5","doi-asserted-by":"publisher","first-page":"20000","DOI":"10.1016\/S0021-9258(19)47210-4","article-title":"Posttranslational regulation of sucrase-isomaltase expression in intestinal crypt and villus cells","volume":"264","author":"Beaulieu","year":"1989","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5735","DOI":"10.1016\/S0021-9258(19)41116-2","article-title":"Human intestinal sucrase-isomaltase. Identification of free sucrase and isomaltase and cleavage of the hybrid into active distinct subunits","volume":"250","author":"Conklin","year":"1975","journal-title":"J. Biol. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1159\/000388787","article-title":"Assay of intestinal disaccharidases","volume":"11","author":"Dahlqvist","year":"1970","journal-title":"Enzym. Act. Hum. Tissue"},{"key":"B8","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1097\/MPG.0B013E3182A27438","article-title":"Maltase-glucoamylase modulates gluconeogenesis and sucrase-isomaltase dominates starch digestion glucogenesis","volume":"57","author":"Diaz-Sotomayor","year":"2013","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B9","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1021\/J100286A023\/ASSET\/J100286A023.FP.PNG_V03","article-title":"Size and shape of sodium deoxycholate micellar aggregates","volume":"91","author":"Esposito","year":"1987","journal-title":"J. Phys. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/J.BBADIS.2016.12.017","article-title":"Molecular pathogenicity of novel sucrase-isomaltase mutations found in congenital sucrase-isomaltase deficiency patients","volume":"1863","author":"Gericke","year":"","journal-title":"Biochim. Biophys. acta. Mol. basis Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"11070","DOI":"10.1074\/jbc.M117.791939","article-title":"Structure-function analysis of human sucrase-isomaltase identifies key residues required for catalytic activity","volume":"292","author":"Gericke","year":"","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1021\/J100443A008\/ASSET\/J100443A008.FP.PNG_V03","article-title":"Shape and size of a nonionic surfactant micelle. Triton X-100 in aqueous solution","volume":"84","author":"Hasko Paradies","year":"1980","journal-title":"J. Phys. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4423","DOI":"10.1073\/PNAS.82.13.4423","article-title":"Transport to cell surface of intestinal sucrase-isomaltase is blocked in the Golgi apparatus in a patient with congenital sucrase-isomaltase deficiency","volume":"82","author":"Hauri","year":"","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B14","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1083\/JCB.101.3.838","article-title":"Expression and intracellular transport of microvillus membrane hydrolases in human intestinal epithelial cells","volume":"101","author":"Hauri","year":"","journal-title":"J. Cell. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1136\/GUTJNL-2016-312456","article-title":"Functional variants in the sucrase\u2013isomaltase gene associate with increased risk of irritable bowel syndrome","volume":"67","author":"Henstr\u00f6m","year":"2018","journal-title":"Gut"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1136\/GUTJNL-2019-319411","article-title":"Impaired cell surface expression and digestive function of sucrase-isomaltase gene variants are associated with reduced efficacy of low FODMAPs diet in patients with IBS-D","volume":"69","author":"Husein","year":"2020","journal-title":"Gut"},{"key":"B17","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/NU13010009","article-title":"Differential effects of sucrase-isomaltase mutants on its trafficking and function in irritable bowel syndrome: Similarities to congenital sucrase-isomaltase deficiency","volume":"13","author":"Husein","year":"2020","journal-title":"Nutr"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.3390\/NU11102290","article-title":"Heterozygotes are a potential new entity among homozygotes and compound heterozygotes in congenital sucrase-isomaltase deficiency","volume":"11","author":"Husein","year":"2019","journal-title":"Nutrients"},{"key":"B19","doi-asserted-by":"publisher","first-page":"6566","DOI":"10.1074\/JBC.275.9.6566","article-title":"Structural determinants required for apical sorting of an intestinal brush-border membrane protein","volume":"275","author":"Jacob","year":"","journal-title":"J. Biol. Chem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1172\/JCI9677","article-title":"Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme","volume":"106","author":"Jacob","year":"","journal-title":"J. Clin. Invest."},{"key":"B21","doi-asserted-by":"publisher","first-page":"6487","DOI":"10.1021\/acs.jafc.6b01816","article-title":"Contribution of the individual small intestinal \u03b1-glucosidases to digestion of unusual \u03b1-linked glycemic disaccharides","volume":"24","author":"Lee","year":"2016","journal-title":"J Agric Food Chem"},{"key":"B22","doi-asserted-by":"publisher","first-page":"31929","DOI":"10.1074\/jbc.M112.351858","article-title":"Modulation of starch digestion for slow glucose release through \u201ctoggling\u201d of activities of mucosal alpha-glucosidases","volume":"287","author":"Lee","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"W580","DOI":"10.1093\/nar\/gkv279","article-title":"The EMBL-EBI bioinformatics web and programmatic tools framework","volume":"43","author":"Li","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1097\/01.mpg.0000421414.95751.be","article-title":"Direct starch digestion by sucrase-isomaltase and maltase-glucoamylase","volume":"55","author":"Lin","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0962-8924(91)90001-P","article-title":"Golgi retention signals: Do membranes hold the key?","volume":"1","author":"Machamer","year":"1991","journal-title":"Trends Cell. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1097\/01.MPG.0000421402.57633.4B","article-title":"Congenital sucrase-isomaltase deficiency: Heterogeneity of inheritance, trafficking, and function of an intestinal enzyme complex","volume":"55","author":"Naim","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"12313","DOI":"10.1016\/S0021-9258(18)98898-8","article-title":"Expression of a full-length cDNA coding for human intestinal lactase-phlorizin hydrolase reveals an uncleaved, enzymatically active, and transport-competent protein","volume":"266","author":"Naim","year":"1991","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7242","DOI":"10.1016\/S0021-9258(18)68634-X","article-title":"Biosynthesis of the human sucrase-isomaltase complex. Differential O-glycosylation of the sucrase subunit correlates with its position within the enzyme complex","volume":"263","author":"Naim","year":"","journal-title":"J. Biol. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"19709","DOI":"10.1016\/S0021-9258(19)77693-5","article-title":"Structure, biosynthesis, and glycosylation of human small intestinal maltase-glucoamylase","volume":"263","author":"Naim","year":"","journal-title":"J. Biol. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1097\/MPG.0000000000001561","article-title":"Improved starch digestion of sucrase-deficient shrews treated with oral glucoamylase enzyme supplements","volume":"65","author":"Nichols","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1073\/pnas.0237170100","article-title":"The maltase-glucoamylase gene: Common ancestry to sucrase-isomaltase with complementary starch digestion activities","volume":"100","author":"Nichols","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3076","DOI":"10.1074\/JBC.273.5.3076","article-title":"Human small intestinal maltase-glucoamylase cDNA cloning: Homology to sucrase-isomaltase","volume":"273","author":"Nichols","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0014-5793(93)80906-B","article-title":"Kin recognition. A model for the retention of Golgi enzymes","volume":"330","author":"Nilsson","year":"1993","journal-title":"FEBS Lett."},{"key":"B34","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1097\/MPG.0B013E31804216FC","article-title":"Luminal substrate \u201cbrake\u201d on mucosal maltase-glucoamylase activity regulates total rate of starch digestion to glucose","volume":"45","author":"Quezada-Calvillo","year":"","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1093\/JN\/137.7.1725","article-title":"Contribution of mucosal maltase-glucoamylase activities to mouse small intestinal starch alpha-glucogenesis","volume":"137","author":"Quezada-Calvillo","year":"","journal-title":"J. Nutr."},{"key":"B36","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/0005-2736(73)90434-3","article-title":"Purification of the human intestinal brush border membrane","volume":"323","author":"Schmitz","year":"1973","journal-title":"Biochim. Biophys. Acta"},{"key":"B37","doi-asserted-by":"publisher","first-page":"17763","DOI":"10.1074\/jbc.M109.078980","article-title":"Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains","volume":"285","author":"Sim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0009-8981(80)90432-5","article-title":"Peptide hydrolases of the human small intestinal mucosa: Distribution of activities between brush border membranes and cytosol","volume":"102","author":"Sterchi","year":"1980","journal-title":"Clin. Chim. Acta."},{"key":"B39","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1515\/BC.2009.077","article-title":"Impact of glycosylation and detergent-resistant membranes on the function of intestinal sucrase-isomaltase","volume":"390","author":"Wetzel","year":"2009","journal-title":"Biol. Chem."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2023.1160860\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:40Z","timestamp":1678233640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2023.1160860\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":39,"alternative-id":["10.3389\/fmolb.2023.1160860"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2023.1160860","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]},"article-number":"1160860"}}