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Abstract

Abstract 

  1. The brush-border membrane of the human small intestine is endowed with a total of seven glycosidases,* which give rise to free monosaccharides by splitting dietary disaccharides and oligosaccharides that arise in the intestinal lumen from the α-amylolysis of starch. The four “maltases” occur as two heterodimers (i.e., the glucoamylase complex and the sucrase-isomaltase complex); the β-glycosidase complex, which is composed of a single type of polypeptide, has two catalytic sites (lactase and glycosylceramidase). Trehalase is composed of a single type of subunit(s) (Table 75-1). These glycosidases are stalked intrinsic proteins of the membrane; the body of the protein mass, including the catalytic sites, protrudes toward the small-intestinal lumen.

  2. The glycosidases, with the exception of trehalase, are synthesized as very large polypeptide chains, each of which has an apparent molecular weight in the range of 200,000 to 250,000. These pro forms are each split into the final forms either extracellularly (as are the α-glucosidase complexes) or mostly intracellularly (the β-glycosidase complex; see Table 75-2). Since the two catalytic domains in each of these complexes belong to a single translational unit, they are subject to the same biologic control mechanism(s).

  3. Mammals other than humans are equipped at birth with the β-glycosidase and the glucoamylase complexes. Sucrase-isomaltase and trehalase develop at the time of weaning, when the β-glycosidase complex begins to decline, eventually reaching a level as low as 5 to 10 percent of that at birth. In contrast, in humans, the brush-border disaccharidases develop before birth, beginning prior to week 10 of gestation, with a developmental burst (particularly in the β-glycosidase complex) a few weeks before birth. The level of the β-glycosidase complex—in effect, the level of lactase activity—remains high throughout adulthood in most white people and a few other races.

  4. The primary site of control in the spontaneous physiological development of sucrase-isomaltase is in all likelihood at the level of transcription. Dietary and hormonal factors also control the levels of disaccharidase activities.

  5. Both secondary and primary (genetic) disaccharidase deficiencies are known, which may lead to malabsorption and intolerance of the corresponding disaccharide(s) but not of the constituent monosaccharides. Diagnosis depends on determination of enzyme activities through small-intestinal biopsies and/or on an oral tolerance test with the corresponding disaccharides. Among the latter, the breath hydrogen test is particularly reliable.

  6. All genetic variants of intestinal disaccharidases are monofactorial and autosomal. The most common polymorphic variant is adult-type hypolactasia, in which intestinal lactase declines in childhood or shortly thereafter to 10 percent or less of the level at birth. It should be considered the normal situation, since it occurs in the majority of human populations (and in essentially all mammals other than humans). The genetic basis of human adult-type hypolactasia is discussed in Chap. 76.

  7. Sucrase-isomaltase deficiency is much rarer and is also genetically heterogeneous.

  8. Congenital lactase deficiency and trehalase deficiency are very rare, and little is known about their molecular basis.

Abstract 

* In this chapter, we use the term disaccharidases to refer to the enzymes listed in Tables 75-1 and 75-2. The term is used even in cases in which the substrates of interest are oligosaccharides or glycosides other than disaccharides.

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