Intestinal β-Galactosidases in Adult Low Lactase Activity1 and
in Congenital Lactase Deficiency

Asp, Nils‐Georg; Dahlqvist, Arne

doi:10.1159/000459416

Cited by 26 publications

(7 citation statements)

References 25 publications

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“…As some minor bands were observed in the electrophoresis gel, a method developed by A. Dahlqvist [30, 311 was followed to prove that no other intestinal P-galactosidases were present in the preparation. Thus, o-nitrophenyl-fi-u-galactopyranoside and p-nitrophenyl-P-D-galactopyranoside were substrates for the enzymic activity, while 2-napthyl-P-~-galactopyranoside was not a substrate, as should be expected if only lactase activity is present [31]. Equally, p-chloromercuribcnzoate did not inhibit the P-galactosidase activity of this preparation, as has been described for lactase activity [30].…”

Section: Resultssupporting

confidence: 65%

Substrate specificity of small‐intestinal lactase

Rivera‐Sagredo

Cañada

Nieto

et al. 1992

European Journal of Biochemistry

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Lactase-phlorizin hydrolase is a disaccharidase present in the small intestine of mammals. This enzyme has two active sites, one being responsible for the hydrolysis of lactose. Lactase activity is thought to be selective towards glycosides with a hydrophilic aglycon. In this work, we report a systematic study on the importance of each hydroxyl group in the substrate molecule for lactase activity. For this purpose, all of the monodeoxy derivatives of methyl b-lactoside and other lactose analogues are studied as lactase substrates. With respect to the galactose moiety, it is shown here that HO-3' and HO-2' are necessary for hydrolysis of the substrates by lactase. Using these chemically modified substrates, it has been confirmed that lactase does not behave as a typical P-galactosidase, since it does not show an absolute selectivity with respect to substitution and stereochemistry at C4' in the galactose moiety of the substrate. However, the glucose moiety, in particular the HO-6, appears to be important for substrate hydrolysis, although none of the hydroxyl groups seemed to be essential. In order to differentiate both activities of the enzyme, a new assay for the phlorizin-hydrolase activity has also been developed.Small-intestinal disaccharidases in higher animals are located in the luminal membrane of intestinal mucose where they hydrolyze the disaccharides in the diet and the oligosaccharides that arise in the intestinal lumen after a-amiIolysis of starch [l, 21. Lactase is the small-intestinal disaccharidase that splits the major 8-glycoside of the diet, lactose, to give glucose and galactose (Scheme 1). The enzyme has been the subject of considerable investigation because of its involvement in the most frequent genetically based syndrome in man, known as adult-type alactasia or lactose intolerance in the adult resulting in a remarkable decrease in lactase activity in adulthood which affects more than 33% of adult humans [I, 3,4].A biological clock appears to exist, causing a marked decline of lactase after weaning, except for individuals whose ancestors are dependent on a substantial consumption of milk and milk-derived products.It has been known for some time that, in addition to lactase activity, the enzyme carries a P-glucosidase activity refered to as phlorizin hydrolase [5-81, which is in fact a glycosylceramidase [9]. The enzyme is therefore named lactasephlorizin hydrolase or the intestinal P-glycosidase complex. We have now carried out a systematic study of the substrate specificity with respect to the lactase site of the bglycosidase complex from sheep small intestine, using chemically modified methyl P-lactoside derivatives. Methyl P-lactoside rather than lactose, has been used as a reference compound in order to simplify the analysis of the reaction mixtures. These chcmically modified substrates have been frequently used in the study of enzyme mechanisms [13 -161 and have proved extremely useful in probing the combining sites for the elucidation of specific interactions between proteins and carb...

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Section: Resultssupporting

confidence: 65%

Substrate specificity of small‐intestinal lactase

Rivera‐Sagredo

Cañada

Nieto

et al. 1992

European Journal of Biochemistry

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“…It could be demonstrated that adults with low lactase activity had a variable residual activity of seemingly normal Scand J Nutr/N%ringsforskning 4/01 lactase, whereas no residual activity could be measured in cases of congenital lactose malabsorption (10). Immunoelectrophoretic studies by Skovbjerg, Sjostrom, Nor&, Gudmand-Hoyer and Fenger (1 l,l2) confirmed that low lactase activity in adults is due to a small amount of normal lactase and not to a modified inactive enzyme.…”

Section: Digestion and Absorption Of Lactosementioning

confidence: 94%

Low intestinal lactase activity - a 40 years perspective

Asp

2001

Näringsforskning

Self Cite

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Low intestinal lactase activity (hypolactasia) was discovered in the early 1960s as a cause of lactose intolerance. Since then, it has become clear that hypolactasia in adults is a normal phenomenon in man as in other mammals. Lactase persistence is a dominant autosomal trait, enriched during thousands of years in cattle-raising populations, where continued high capacity to digest lactose might have been related to better health and more children. Hypolactasia is a cause of lactose intolerance, but it should be noted that most people with hypolactasia tolerate considerable amounts of milk products, especially when distributed throughout the day and taken with meals. Perceived intolerance to a few grams of lactose may be due to other food components or related to a general "sensitivity" of the gastrointestinal tract. Keywords: Hypolactasia, lactose intolerance, malabsorption, milk TerminologyThe original term lactase deficiency was questioned during the 70s, when it became clear that down-regulation of lactase is a normal phenomenon in man as in other mammals. Primary low intestinal lactase activity, hypolactasia and lactase restriction are terms considered more appropriate to describe the low lactase activity in adults due to down-regulation. Lactase persistence is a logical corresponding term for keeping a high intestinal lactase activity throughout life. Secondary hypolactasia means that the low intestinal lactase activity is due to damage of the small-intestinal mucosa as a result of infection, infestation, czliac disease, allergy or malnutrition. The "normal" lactase activity will then be restored when the underlying condition is cured.Lactose malabsorption or lactose maldigestion or low lactose digestion capacity means that lactose is incompletely absorbed in the small intestine, with the result that lactose passes to the large intestine. This is demonstrated through a lactose tolerance test, in which a standardised amount of lactose, usually 50 g, is given. A small blood-glucose elevation, a small blood-galactose elevation, or a small urinary galactose excretion in a lactose tolerance test with ethanol (to inhibit galactose metabolism), or an elevated breath hydrogen excretion (as a result of fermentation) are measurements used to demonstrate lactose malabsorption, which is almost always due to low intestinal lactase activity.Lactose intolerance means the experience of symptoms due to lactose malabsorption. Obviously, lactose intolerance is dosedependent, and it has been demonstrated repeatedly that hypolactasia does not always mean intolerance to normal amounts of milk products in the diet.Milk intolerance can be due to lactose intolerance, but also to milk protein allergy, and possibly related to other milk components.Pseudolactose intolerance not always means gastrointestinal symptoms related to milk in subjects with lactase persistence.

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“…The lactase was characterized in more detai l and separated fro m other smal l intestinal !3-galactosidases (17) , and analyses of the thre e different small intestina l mucosa l !3-galactosidases in small intes tinal biopsies from patie nts with low lactase activit y showed that there was a decrease in the bru sh border lact ase but not in the other !3-galactosidas es (18). On the other hand , children with congenital lactase deficiency had practically no brus h-border lactase activit y left (19) .…”

Section: Dedication To Arne Dahlqvistmentioning

confidence: 98%

Dedication to Arne Dahlqvist

1985

J. pediatr. gastroenterol. nutr.

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Intestinal β-Galactosidases in Adult Low Lactase Activity1 and in Congenital Lactase Deficiency

Cited by 26 publications

References 25 publications

Substrate specificity of small‐intestinal lactase

Substrate specificity of small‐intestinal lactase

Low intestinal lactase activity - a 40 years perspective

Dedication to Arne Dahlqvist

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