Sucrase/isomaltase

The principle of active-site-directed inactivation of glycosidases by gly-con-related epoxides can be extended to compounds having an exocyclic oxirane ring, either directly attached to the six-membered ring (32) or at some distance (33,34). Studies with -o-glucosidase from sweet almonds and intestinal sucrase-isomaltase revealed that, in spite of the higher intrinsic reactivity of these epoxides, this shift of the position of the epoxide function causes a 10- to 30-fold decrease of kj(max)/Ki, an effect which probably reflects the limited flexibility of the catalytic groups involved in the epoxide reaction. 

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... 

Zweibaum A, Traidou N, Kedinger M et al. (1983) Sucrase-isomaltase a marker of foetal and malignant epithelial cells of the human colon. Int J Cancer 32 407 112 Zweibaum A, Pinto M, Chevalier G et al. (1985) Enterocytic differentiation of a subpopulation of the human colon tumor cell line HT-29 selected for growth in sugar-free medium and its inhibition by glucose. J Cell Physiol 122 21-29... 

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. 

Insufficient digestive agents Biliary obstruction Chronic liver failure Chronic pancreatitis Cystic fibrosis Lactase deficiency Pancreatic cancer Pancreatic resection Sucrase-isomaltase deficiency... 

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 selipophilic acids near the M terminus that anchors the enzyme to the membrane is underlined. The first few are leucine isoJeudne, valine, and isoleucine,... 

Proteins also can be classified as those that are soluble and remain in the cell, those that are membrane-bound in the cell, and those that are soluble and secreted from the cell. The specific sequence and nature of the amino acids in the polypeptide chain determine the eventual location of the polypeptide in the cell. Insulin, a secretrxl polypeptide, is of great interest to nutritionaJ scientists and the medical profession, Sucrase-isomaltase is a membrane-bound protein of occasional interest in nutrition. 

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. 

FIGURE 2.43 Orientation of sucrase-isomaltase, a membrane-bound enzvme. 

Hunziker, W., Spiess, M., Semenza, C., and Lodish, H. F. (1986). The sucrase-isomaltase compje) I rimary structure, membrane orientation, and evolution of a stalked, intrinsic brush border protein. Ceff 46,227-234. 

Sucrose (saccharose) Unsuitable in hereditary fructose intolerance, glucose/ galactose malabsorption syndrome, or sucrase-isomaltase deficiency... 

FIGURE 1.26 Sequence of events during insertion of sucrase-isomaltase into the endoplasmic reticulum. 

FIGURE 1.27 First 35 amino acids of sucrase-isomaltase. 

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 and Trehalase Deficiencies and Monosaccharide Malabsorption... 

Sucrase-isomaltase deficiency usually presents clinically in infancy when sucrose and fruit are introduced in the diet, " but sometimes first presents in adulthood. The deficiency is rare in Caucasians, but more common in Eskimo groups. Deficiencies of both lactase and sucrase-isomaltase may occur secondary to other small bowel diseases (e.g., cehac disease, Crohn s disease,or acute gastroenteritis). Trehalase deficiency is a rare disorder,except in Greenland, where it occurs in 8% of the population. It is manifested by diarrhea following the ingestion of mushrooms. 

Sucrase-isomaltase deficiency can be investigated by using 50 g sucrose instead of lactose. An increase in breath hydrogen of >20 ppm (20 pL/L) within 2 hours is diagnostic. It is rarely necessary to test for trehalase deficiency, although a breath test using 25 g trehalose has been described. ... 

Muldoon C, Maguire P, Gleeson F. Onset of sucrase-isomaltase deficiency in late adulthood. Am J Gastroenterol 1999 94 2298-9. 

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