Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.26 (invertase)
 4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sucrase-isomaltase deficiency is an inherited disaccharidase deficiency that leads to malabsorption of sucrose, with resulting diarrhea and abdominal distention and cramps. We investigated the sucrose-splitting effect of viable yeast cells in eight children with congenital sucrase-isomaltase deficiency, by means of the sucrose hydrogen breath test. This test is based on the fact that hydrogen is released from the malabsorbed sucrose by the colonic microflora. We found that 0.3 g of lyophilized Saccharomyces cerevisiae, given after loading with 2 g of sucrose per kilogram of body weight, reduced hydrogen excretion in all patients, on average by 70 percent, in parallel with a complete loss or evident reduction of clinical symptoms. In vitro, lyophilized and fresh S. cerevisiae (fresh baker's yeast) had appreciable sucrase activity, a low isomaltase and maltase activity, and virtually no lactase activity. The sucrase activity was more inhibited by undiluted than by diluted gastric juice. We conclude that patients with congenital sucrase-isomaltase deficiency who intentionally or unintentionally consume sucrose can ameliorate the malabsorption by subsequently ingesting a small amount of viable yeast cells, preferably on a full stomach.
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PMID:Enzyme-substitution therapy with the yeast Saccharomyces cerevisiae in congenital sucrase-isomaltase deficiency. 355 46

Phenotype II of congenital sucrase-isomaltase deficiency in man is characterized by a retention of the brush border protein sucrase-isomaltase (SI) in the ER/cis-Golgi intermediate compartment (ERGIC) and the cis-Golgi. The transport block is due to the substitution of a glutamine by a proline at amino acid residue 1098 that generates a temperature-sensitive mutant enzyme, SI(Q1098P), the transport of which is regulated by several cycles of anterograde and retrograde transport between the ER and the cis-Golgi (Propsting, M. J., Jacob, R. and Naim, H. Y. (2003). J. Biol. Chem. 278, 16310-16314). A quality control beyond the ER has been proposed that implicates a retention signal or a folding determinant elicited by the Q1098P mutation. We have used alanine-scanning mutagenesis to screen upstream and downstream regions flanking Q(1098) and identified a putative motif, F(1093)-x-F(1095)-x-x-x-F(1099) that is likely to be implicated in sensing the folding and subsequent trafficking of SI from the ER to the Golgi. The characteristics of this motif are three phenylalanine residues that upon substitution by alanine generate the temperature-sensitive SI(Q1098P) phenotype. This mutant protein undergoes transport arrest in the ERGIC and cis-Golgi compartments and acquires correct folding and functional activity at reduced temperatures as a consequence of cycles of anterograde and retrograde transport between the ER and cis-Golgi. Other amino acid residues in this motif are not significant in the context of phenotype II. We propose that the phenylalanine cluster is required for shielding a folding determinant in the extracellular domain of SI; substitution of a Q by a P at residue 1098 of sucrase disrupts this determinant and elicits retention of SI(Q1098P) in ERGIC and cis-Golgi in phenotype II of CSID.
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PMID:A phenylalanine-based folding determinant in intestinal sucrase-isomaltase that functions in the context of a quality control mechanism beyond the endoplasmic reticulum. 1594 3