Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency
Congenital sucrase-isomaltase deficiency (CSID) is a rare metabolic intestinal disorder with reduced or absent activity levels of sucrase-isomaltase (SI). Interestingly, the main symptoms of CSID overlap with those in irritable bowel syndrome (IBS), a common functional gastrointestinal disorder with...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/1/9 |
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| author | Diab M. Husein Sandra Rizk Hassan Y. Naim |
| author_facet | Diab M. Husein Sandra Rizk Hassan Y. Naim |
| author_sort | Diab M. Husein |
| collection | DOAJ |
| description | Congenital sucrase-isomaltase deficiency (CSID) is a rare metabolic intestinal disorder with reduced or absent activity levels of sucrase-isomaltase (SI). Interestingly, the main symptoms of CSID overlap with those in irritable bowel syndrome (IBS), a common functional gastrointestinal disorder with unknown etiology. Recent advances in genetic screening of IBS patients have revealed rare SI gene variants that are associated with IBS. Here, we investigated the biochemical, cellular and functional phenotypes of several of these variants. The data demonstrate that the SI mutants can be categorized into three groups including immature, mature but slowly transported, and finally mature and properly transported but with reduced enzymatic activity. We also identified SI mutant phenotypes that are deficient but generally not as severe as those characterized in CSID patients. The variable effects on the trafficking and function of the mutations analyzed in this study support the view that both CSID and IBS are heterogeneous disorders, the severity of which is likely related to the biochemical phenotypes of the SI mutants as well as the environment and diet of patients. Our study underlines the necessity to screen for SI mutations in IBS patients and to consider enzyme replacement therapy as an appropriate therapy as in CSID. |
| first_indexed | 2024-03-10T13:51:53Z |
| format | Article |
| id | doaj.art-fd0b7b9e0aba431eb792597b63990303 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T13:51:53Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-fd0b7b9e0aba431eb792597b639903032023-11-21T02:04:28ZengMDPI AGNutrients2072-66432020-12-01131910.3390/nu13010009Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase DeficiencyDiab M. Husein0Sandra Rizk1Hassan Y. Naim2Department of Biochemistry, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, GermanyDepartment of Natural Sciences, Lebanese American University, Beirut 1102-2801, LebanonDepartment of Biochemistry, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, GermanyCongenital sucrase-isomaltase deficiency (CSID) is a rare metabolic intestinal disorder with reduced or absent activity levels of sucrase-isomaltase (SI). Interestingly, the main symptoms of CSID overlap with those in irritable bowel syndrome (IBS), a common functional gastrointestinal disorder with unknown etiology. Recent advances in genetic screening of IBS patients have revealed rare SI gene variants that are associated with IBS. Here, we investigated the biochemical, cellular and functional phenotypes of several of these variants. The data demonstrate that the SI mutants can be categorized into three groups including immature, mature but slowly transported, and finally mature and properly transported but with reduced enzymatic activity. We also identified SI mutant phenotypes that are deficient but generally not as severe as those characterized in CSID patients. The variable effects on the trafficking and function of the mutations analyzed in this study support the view that both CSID and IBS are heterogeneous disorders, the severity of which is likely related to the biochemical phenotypes of the SI mutants as well as the environment and diet of patients. Our study underlines the necessity to screen for SI mutations in IBS patients and to consider enzyme replacement therapy as an appropriate therapy as in CSID.https://www.mdpi.com/2072-6643/13/1/9sucrase-isomaltasecongenital sucrase-isomaltase deficiencyirritable bowel syndromeprotein trafficking |
| spellingShingle | Diab M. Husein Sandra Rizk Hassan Y. Naim Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency Nutrients sucrase-isomaltase congenital sucrase-isomaltase deficiency irritable bowel syndrome protein trafficking |
| title | Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency |
| title_full | Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency |
| title_fullStr | Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency |
| title_full_unstemmed | Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency |
| title_short | Differential Effects of Sucrase-Isomaltase Mutants on Its Trafficking and Function in Irritable Bowel Syndrome: Similarities to Congenital Sucrase-Isomaltase Deficiency |
| title_sort | differential effects of sucrase isomaltase mutants on its trafficking and function in irritable bowel syndrome similarities to congenital sucrase isomaltase deficiency |
| topic | sucrase-isomaltase congenital sucrase-isomaltase deficiency irritable bowel syndrome protein trafficking |
| url | https://www.mdpi.com/2072-6643/13/1/9 |
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