Enzyme sucrase-isomaltase

This enzyme [EC 3.2.1.10] (also referred to as oUgo-1,6-glucosidase, sucrase-isomaltase, and limit dextrinase) catalyzes the hydrolysis of l,6-o -D-glucosidic linkages in isomaltose and dextrin products generated from starch and glycogen via a-amylase. See also Sucrase... 

Harms, H. K., Bertele-Harms, R. M., and Bruer-Kleis, D. (1987), Enzyme-substitution therapy with the yeast Saccharomyces cerevisiae in congenital sucrase-isomaltase deficiency, N. Engl. J. Med., 316,1306-1309. 

A variety of membrane-bound proteins are of vital interest to the medical and nutritional ientist, because defects or changes in these proteins can cause such problems as lactose intolerance, cardiovascular disease, cystic fibrosis, and diabetes. Sucrase-isomaltase, an enzyme of the small intestine, is a membrane-bound protein, bound to the plasma membrane of the cnterocyte (gut cell). Part of the production of this enzyme is depicted in Figure 1,26. in Step 1, the polypeptide chain is polymerized on the ribosome (shown in black). In Step 2, part of the amino add chain near the N terminus crosses the membrane of the ER into the lumen but some of the amino acids at the N terminus remain outside. Step 3 shows the protein assuming a three-dimensional shape within the lumen both the C and N... 

The first 35 amino acids in the sesucrase-isomaltase are shown in Figure 1.27, The stretch of lipophilic acids near the M terminus that anchors the enzyme to the membrane is underlined. The first few are leucine isoJeudne, valine, and isoleucine,... 

Dextrins are hydrolyzed by a membrane-bound enzyme isomaltase, which occurs in the same polypeptide chain as sucrase, the enzyme that hydrolyzes sucrose, Two active sites (catalytic sites) reside on one polypeptide chain. The entire protein is called sucrase-isomaltase. Enzymes containing more than one active site on one polypeptide chain are called multi functional. The orientation of sucrase-isomaltase in the gut cell, or enterocyte, is shown in Figure 2.43. Both active sites are situated in the lumen of the gut the N-terminal region is anchored in the membrane. Each of the active sites of sucrase-isomaltase is capable of hydrolyzing maltose. Perhaps a better, although cumbersome, name for the enzyme would be sucrase/maltase-isomaltase/maliase. The isomaltase catalytic site is closest to the membrane, whereas the sucrasc site is the C-terminal portion of the enzyme. 

The brush border enzymes with disaccharidase and ohgosaccharidase activity are listed in Table 48-1. The sucrase-isomaltase complex comprises most of the sucrase, isomaltase, and maltase (80%) activity of the small intestine. It hydrolyzes sucrose to its constituent monosaccharides, cleaves glucose from a-limit dextrins with 1,6 bonds, and hydrolyzes maltose. The activity of the complex is fourfold to fivefold greater in the jejunum than in the ileum. Changes in diet have a marked effect on the expression of the complex starvation leads to a rapid decline in activity, which is rapidly restored on refeeding. AH small intestinal saccha-ridases may decrease with infection or inflammation of the small bowel to the extent that carbohydrate malabsorption... 

Sucrase-isomaltase complex An enzyme complex comprised of two enzyme units. Both units have high a-l,4-glucosidase activity and will hydrolyze maltose and maltotriose to glucose. The sucrase unit will also hydrolyze sucrose to fructose and glucose, whereas the isomaltase unit will hydrolyze a-1,6 bonds found in isomaltose and the limit dextrins of starch. 

Fig. 27.5. The major portion of the sucrase-isomaltase complex, containing the catalytic sites, protrudes from the absorptive cells into the lumen of the intestine. Other domains of the protein form a connecting segment (stalk), and an anchoring segment that extends through the membrane into the cell. The complex is synthesized as a single polypeptide chain that is split into its two enzyme subunits extracellularly. Each subunit is a domain with a catalytic site (sucrase-maltase) and isomaltase-maltase sites. In spite of their maltase activity, these catalytic sites are often called just sucrase and isomaltase.

The intestinal surface membrane from rats contains both (1 4)-a- and (1 6)-a-D-glucosidase (-glucanase) activities and these enzymes have been given the trivial names of sucrase and isomaltase , respectively. The concurrent action of the sucrase and isomaltase active sites of the hybrid sucrase-isomaltase enzyme complex has been studied on the hexasaccharide (1). Hydro-... 

Oligo-1,6-D-glucosidase-sucrose a-D-glucohydrolase ( sucrase-isomaltase ) is an intestinal membrane enzyme consisting of two active moieties, each with its hydrolytic site available for nutrient digestion at the luminal-cell interface. 

Studies on the enzyme complex oligo-l,6-D-glucosidase-sucrose a-D-glucohydro-lase ( sucrase-isomaltase ) of the AB intestinal brush border membrane have shown that a hydrophobic section of the oligo-l,6-D-glucosidase is responsible for binding of the complex to the membrane (see p. 522). ... 

The specificity of conduritol B epoxide is such that -glucosidases from widely differing sources have been found to react with loss of enzymic activity from various Aspergillus species, > yeast, snail Helix pomatia) sweet almonds, and mammals. The only exceptions have been the / -glucosidases from garbanzo plants Cicer arietum L.) and from Alocasia macrorrhiza The only other enzymes that have been found to be covalently inhibited are a-glucosidase from yeast Saccharo-myces cerevisiae) and the sucrase-isomaltase complex from rabbit small intestine. ... 

The time dependence of the inhibition usually follows a first-order rate law. Epoxide concentrations necessary to achieve more than 98% inhibition in about 8 hr are in the range of 0.2 to 2 mAf (40 mM with sucrase-isomaltase ). Deviations may occur that are due to an enzyme-catalyzed reaction of the epoxide with halide ions in the medium high concentrations of these ions should be avoided. If salt is necessary to keep the enzyme in solution, sodium perchlorate or another salt with a nonnucleophilic anion should be used. 

Sucrase—isomaltase is a bifunctional enzyme that catalyses the hydrolysis of sucrose to glucose and fructose, and of isomaltose to two molecules of glucose. 

Rarely, people may lack sucrase—isomaltase, maltase and/or trehalase. This may be either a genetic lack of the enzyme or an acquired loss as a result of intestinal infection, when all four disaccharidases are lost. These people are intolerant of the sugar(s) that... 

An intestinal disaccharidase which catalyses the hydrolysis of sucrose into glucose and fructose. A deficiency of the enzyme occurs, along with a deficiency of the other intestinal dis-accharidases, in conditions where there is generalised disease of the intestinal wall. A congenital deficiency of sucrase, usually co-existing with isomaltase deficiency, can occur. Acquired sucrase-isomaltase deficiency has also been described but is much rarer. 

Sucrase-isomaltase deficiency Urea cycle enzyme deficiencies Phenylketonuria... 

A case similar to the slow, practically irreversible inhibition of jack bean a-D-mannosidase by swainsonine is represented by the interaction of castanospermine with isomaltase and rat-intestinal sucrase. Whereas the association constants for the formation of the enzyme-inhibitor complex were similar to those of other slow-binding glycosidase inhibitors (6.5 10 and 0.3 10 M s for sucrase and isomaltase, respectively), the dissociation constant of the enzyme-inhibitor complex was extremely low (3.6 10 s for sucrase) or could not be measured at all (isomaltase), resulting in a virtually irreversible inhibition. Danzin and Ehrhard discussed the strong binding of castanospermine in terms of the similarity of the protonated inhibitor to a D-glucosyl oxocarbenium ion transition-state, but were unable to give an explanation for the extremely slow dissociation of the enzyme-inhibitor complex. 

Isomaltase-sucrase deficiency This enzyme deficiency results in an intolerance of ingested sucrose. This disorder is found in about ten percent of Greenland s Eskimos, whereas two percent of North Americans are heterozygous for the deficiency. Treatment is to withhold dietary sucrose. 

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