Defective SI does not hydrolyze Mal

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Mutations that disrupt the catalytic activity or strongly interfere with proper folding, glycosylation and transport of SI (sucrase-isomaltase) block the cleavage of maltose (Mal) to glucose in the gut lumen. Affected individuals can develop severe diarrhea; this symptom is managed by excluding indigestible sugars from the diet (Gray et al. 1976; Ritz et al. 2003; Semenza et al. 1965). A variety of SI mutant alleles have been described. Three missense mutations that are associated with severe loss of SI activity in vivo are annotated here (Alfalah et al. 2009;,Ouwendijk et al. 1996; Sander et al. 2006; Spodsberg et al. 2001). All missense mutant alleles that have been characterized to date encode proteins that fail to reach the lumenal plasma membrane or cannot associate stably with it; one missense mutation not annotated here encodes a polypeptide that undergoes an intracellular cleavage and is secreted as the active enzyme (Jacob et al. 2000).
Literature References
PubMed ID Title Journal Year
11340066 Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder

Jacob, R, Alfalah, M, Zimmer, KP, Spodsberg, N, Naim, HY

J. Biol. Chem. 2001
8609217 Congenital sucrase-isomaltase deficiency. Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment

Fransen, JA, Ginsel, LA, Hollenberg, CP, Moolenaar, CE, Ouwendijk, J, Naim, HY, Peters, WJ

J. Clin. Invest. 1996
14724820 Congenital sucrase-isomaltase deficiency because of an accumulation of the mutant enzyme in the endoplasmic reticulum

Jacob, R, Alfalah, M, Zimmer, KP, Ritz, V, Naim, HY, Schmitz, J

Gastroenterology 2003
19121318 Compound heterozygous mutations affect protein folding and function in patients with congenital sucrase-isomaltase deficiency

Keiser, M, Alfalah, M, Zimmer, KP, Leeb, T, Naim, HY

Gastroenterology 2009
5849827 Lack of some intestinal maltases in a human disease transmitted by a single genetic factor

Semenza, G, Rubino, A, Auricchio, S, Prader, A, Welsh, JD

Biochim. Biophys. Acta 1965
16329100 Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption

Keiser, M, Alfalah, M, Korponay-Szabo, I, Sander, P, Leeb, T, Kovács, JB, Naim, HY

Hum. Mutat. 2006
10903344 Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme

Jacob, R, Zimmer, KP, Naim, HY, Schmitz, J

J. Clin. Invest. 2000
1256470 Sucrase-isomaltase deficiency. Absence of an inactive enzyme variant

Gray, GM, Townley, RR, Conklin, KA

N. Engl. J. Med. 1976
Catalyst Activity

alpha-1,4-glucosidase activity of SI mutant dimers [plasma membrane]

Normal reaction
Functional status

Loss of function of SI mutant dimers [plasma membrane]

Orthologous Events
Cite Us!