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At least 19 recordsLinked to original sources
PubMed1990

Age dependency of the lactase persistence and lactase restriction phenotypes among children in Sri Lanka and Britain.

All neonates are born with intestinal lactase activity. In most of them the intestinal lactase activity is lost during childhood (lactase restriction phenotype). In a minority of children normal intestinal lactase activity is retained (lactase persistence phenotype). In this study the progression of the lactase restriction phenotypes has been studied in 94 Sri Lankan children by oral lactose loads and 162 British children by intestinal lactase estimation (adult Sri Lankans and British predominantly belong to the lactase restriction and lactase persistence phenotypes, respectively). Lactase was present in infancy at birth in all Sri Lankan children and declined around the age of eight years, the majority (59 per cent) of the 10-15-year-olds belonging to the lactase restriction phenotype. In contrast the majority of the British children (95 per cent of all the British children studied) demonstrated the lactase persistence phenotype. The low prevalence rate of the restriction phenotype found among British children was largely contributed by children of African and Asian origin.

Age Factors↗
PubMed1989

New insights into lactase and glycosylceramidase activities of rat lactase-phlorizin hydrolase.

Lactase-phlorizin hydrolase, a small intestinal disaccharidase, has been considered mainly an enzyme important only for the hydrolysis of lactose. After weaning in most mammals lactase-specific activity falls markedly, and, functionally, adult mammals are considered to be lactase deficient. However, the persistence of low levels of lactase activity in adulthood has never been explained. In addition, it has been suggested that lactase-phlorizin hydrolase is associated with glycosylceramidase activity when the enzyme is prepared by column chromatography, but it is unclear whether this represents copurified activities or two catalytic sites on one peptide. The developmental patterns of lactase-phlorizin hydrolase and other disaccharidases were investigated in homogenates of total rat small intestine; lactase and several glycosylceramidases were measured in immunoprecipitates from these homogenates using a monoclonal antibody. The developmental pattern of total lactase activity showed a steady 2.3-fold increase to adult levels (specific activity decreased eightfold), whereas total phlorizin-hydrolase activity increased 10.7-fold (specific activity decreased threefold). As expected, levels of both total and specific sucrase and maltase activities increased during development. In lactating rats total lactase activity showed a significant increase compared with adult males. The developmental pattern of the enzyme activities for the glycolipid substrates was similar to that found for lactase, and the immunoprecipitated enzyme showed a 40- to 55-fold higher affinity for the glycolipids than for lactose. Galactosyl- and lactosylceramide inhibited lactose hydrolysis by 38%, without a competitive pattern, suggesting two different active sites for lactose and glycolipid hydrolysis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1989

Yogurt and fermented-then-pasteurized milk: effects of short-term and long-term ingestion on lactose absorption and mucosal lactase activity in lactase-deficient subjects.

Lactase-deficient subjects absorb lactose in yogurt more effectively than lactose in other dairy products. However, as all previous studies were performed without a double-blind design and only after a single ingestion of the test product, the mechanism of this enhanced absorption remains unclear. The aims of this double-blind study were 1) to evaluate lactose absorption after prolonged ingestion of yogurt and fermented-then-pasteurized milk (FPM) and 2) to assess the modification of the lactase activity of the duodenal mucosa. In 16 lactase-deficient subjects we confirmed that yogurt enhances lactose digestion, this beneficial effect being destroyed by pasteurization. Moreover, the long-term (8 d) ingestion of either yogurt or FPM does not modify the results of hydrogen breath tests in comparison with a 24-h ingestion. The mucosal lactase (Dahlquist method) and beta-galactosidase (ONPG method) activities were not significantly modified by yogurt or FPM ingestion. These results suggest that in lactase-deficient subjects no adaptation occurs after eating yogurt or FPM and that the increased lactose absorption in yogurt must be mainly related to an intraluminal process.

Adolescent↗
PubMed1992

Location of the two catalytic sites in intestinal lactase-phlorizin hydrolase. Comparison with sucrase-isomaltase and with other glycosidases, the membrane anchor of lactase-phlorizin hydrolase.

Lactase-phlorizin hydrolase was isolated by immunoadsorption chromatography from rabbit brush-border membrane vesicles. Inactivation of the enzyme with [3H]conduritol-B-epoxide, a covalent active site-directed inhibitor, labeled glutamates at positions 1271 and 1747. Glu1271 was assigned to lactase, Glu1747 to phlorizin hydrolase activity. In contrast, the nucleophiles in the active sites of sucrase-isomaltase are aspartates (Asp505 and Asp1394). Asp505 is a part of the isomaltase active site and is localized on the larger subunit, which carries the membrane anchor also, while Asp1394 is a part of the active of sucrase. Alignment of these 2 nucleophilic Glu residues in lactase-phlorizin hydrolase and of their flanking regions with published sequences of several other beta-glycosidases allows the classification of the configuration retaining glycosidases into two major families: the "Asp" and the "Glu" glycosidases, depending on the carboxylate presumed to interact with the putative oxocarbonium ion in the transition state. We offer some predictions as to the Glu acting as the nucleophile in the active site of some glycosidases. By hydrophobic photolabeling, the membrane-spanning domain of lactase-phlorizin hydrolase was directly localized in the carboxyl-terminal region thus confirming this enzyme as a monotopic type I protein (i.e. with Nout-Cin orientation) of the brush-border membranes. A simplified version of the Me2+ precipitation method to efficiently and simply prepare brush-border membrane vesicles is also reported.

1-Deoxynojirimycin↗
PubMed1990

Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans.

Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption.

Adult↗
PubMed1991

Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase.

Lactase-phlorizin hydrolase (LPH) splits lactose in the small intestine. LPH activity is high in the suckling; in many human populations the activity declines in adults, leading to adult-type hypolactasia, whereas in other populations the high LPH activity persists in adults. In the present work, we compared LPH sequences at the gene and cDNA level among adult subjects with high and low LPH activity. The complete intron-exon organization, including the sequences of all 17 exons and of the borders of all introns (as well as about 1,000 bp of 5' flanking region), was established for the cloned chromosomal LPH gene of a subject with persistence of lactase. Using PCR, we directly sequenced the exons of a hypolactasic subject. Except for silent mutations and the unknown linkage phase at two heterozygous positions, both coding sequences were identical. We further examined the LPH mRNA of a hypolactasic subject by S1 mapping and by sequencing a set of overlapping PCR products produced from cDNA templates. Except for allelic differences, the LPH sequence of the hypolactasic subject was identical to that of the LPH cDNAs of three subjects with persistence of lactase (one cDNA isolated previously by cloning and two characterized in the present work by PCR). No allele was peculiar to the hypolactasic subject. We conclude that humans with high or low levels of lactase can code for identical LPH enzymes.

Amino Acid Sequence↗
PubMed1976

[Azoindoxyl methods for the histochemical investigation of hydrolases. I. Lactase (lactase-beta-glucosidase complex) (author's transl)].

An azoindozyl method for the histochemical demonstration of lactase (lactase-beta-glucosidase complex) is described. The incubation medium consists of 5 mg 5-Br-4-Cl-3-indolyl-beta-D-fucoside (dissolved in 0.5 ml N,N-dimethylformamide) and 0.02 ml hexazotized prosaniline in 10 ml 0.1 M citric acid phosphate buffer, pH 6-6.5. By means of this method lactase can be exactly localized in the brush border of the enterozytes in the jejunum of suckling rats. Compared to the corresponding indigogenic method the azoindoxyl reaction proceeds faster and the reaction product is often precipitated more precisely.

Animals↗
PubMed1975

Suitability of the azocoupling reaction with 1-naphthyl-beta-D-glucoside for the histochemical demonstration of lactase (lactase-beta-glucosidase complex) in human enterobiopsies.

The suitability of the simultaneous azocoupling reaction with 1-naphthyl-beta-D-glucoside and hexazonium-p-rosanilin in the detection of the activity of lactase (or lactase-beta-glucosidase complex) in jejunal biopsies of patients with various forms of the malabsorption syndrome was tested. Results were compared with those obtained with the indigogenic method using 4-Cl-5-Br-3-indolyl-beta-D-fucoside which is the method of choice. Both methods gave identical results as far as the relative intensity of the brush border staining was concerned. The azocoupling method applied in unfixed cold microtome sections can be recommended for the routine diagnostics of the malabsorption syndrome when the indolyl substrate is not available.

Adult↗
PubMed1990

Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development.

The development of rat intestinal lactase-specific activity displays a well-known post-weaning decline. In contrast, total lactase activity increases to reach maximal levels around weaning, and remains high subsequently. In order to elucidate the molecular basis for these patterns, a rat lactase cDNA was isolated and characterized, and used in the quantification of lactase mRNA during development. This lactase cDNA uniquely hybridized to a 6.8-kilobase mRNA in the small intestine. To assess the amount of lactase mRNA encoding for lactase enzyme activity in the small intestine, total intestinal RNA was isolated and analyzed by Northern and dot-blot hybridization. The pattern of total lactase mRNA during development followed that of total lactase activity, suggesting that over this time span the level of lactase activity is primarily controlled at the transcriptional level. However, the magnitude of increase of total lactase activity during lactation compared to that of total lactase mRNA suggests that additional mechanisms are involved in regulating lactase levels. Analysis of the regional distribution of lactase mRNA along the small intestine at 14 days revealed that mRNA was high in the proximal three regions, but was dramatically lower in the distal regions. Total lactase activity, in contrast, displayed maximum activity in the mid-intestine with decreased levels both proximally and distally. Thus, lactase activity in the intestine appears to be regulated during development predominantly by transcriptional mechanisms, while alterations during lactation, and along the proximal to distal gradient, are the result of other control mechanisms.

Aging↗
PubMed1991

Posttranslational cleavage of rat intestinal lactase occurs at the luminal side of the brush border membrane.

The intestinal sucrase-isomaltase precursor is cleaved at the brush border membrane by luminal proteases. Whether the lactase precursor also is cleaved by luminal proteases is uncertain. Lactase synthesis and processing was studied in 0- and 15-day-old rats after IP administration of [35S]methionine, and changes in precociously cortisone-induced sucrase-isomaltase were used as an internal control. Mucosal lactase and sucrase-isomaltase were separately immunoprecipitated and analyzed by autoradiography after electrophoresis. In both 0- and 15-day-old rats, mucosal lactase appeared as a 200K lactase precursor band at 30 minutes and as 200K and 225K lactase precursor bands at 60 minutes and was cleaved to form a 130K lactase band 120-240 minutes after labeling; sucrase-isomaltase similarly appeared as 210K and 220K bands at 30-60 minutes and was cleaved to form 140K I and 120K S subunits by 240 minutes in day 15 rats. To determine the role of luminal proteases, intestinal segments were isolated in situ and the luminal contents were flushed 30 minutes after labeling. Unflushed segments were used as controls. Only lactase precursor and sucrase-isomaltase precursor were present 240 minutes after labeling in flushed intestinal segments, but lactase precursor and sucrase-isomaltase precursor were cleaved in unflushed segments. Addition of trypsin or elastase into the lumen of flushed segments resulted in partial cleavage of lactase precursor but not of sucrase-isomaltase precursor. Luminal contents collected from the small intestine of day 15 rats 120 and 240 minutes after labeling showed 35S-labeled 130K and 80K polypeptides in lactase immunoprecipitates. It is concluded that intestinal lactase is synthesized as lactase precursor and transported to brush border membrane and cleaved by luminal proteases, and the amino end polypeptide cleaved from lactase precursor is released into the lumen.

Animals↗
PubMed1989

Control of lactase in human adult-type hypolactasia and in weaning rabbits and rats.

Lactase is an enterocyte brush-border membrane beta-glycosidase that splits lactose, the sugar of milk. In mammals, including many human populations, intestinal lactase activity is very high in the suckling and declines to low levels after weaning. There are two human adult lactase phenotypes, one in which high lactase activity persists and another in which it declines. Two alleles have been postulated to explain these different phenotypes. In the present study lactase mRNA levels have been investigated in the small intestine (a) of rabbits and rats, at different ages, considered as models for mammals, and (b) of human adults with the two lactase phenotypes. In rabbits and rats, high levels of lactase mRNA are present up to the weaning period, a time at which a consistent decrease of this mRNA is found, a decrease that parallels that of lactase activity. It is surprising that after this period adult animals of both species express again high levels of lactase mRNA, whereas lactase activity remains at very low levels. Our results suggest that in the adult rabbits and rats the main control of lactase gene expression is likely to be at a posttranscriptional level. Similarly, in man no clear difference was found at the RNA level between adults with hypolactasia and adults with persistent high lactase activity, a result that also indicates a posttranscriptional control of lactase expression.

Adult↗
PubMed1975

Correlation of lactase activity, lactose tolerance and milk consumption in different age groups.

Small intestinal lactase activity in the health adult is either the same as in early infancy or may drop to very low levels. The behavior of the enzymatic state varies with the ethnic group studied. In those adults with low lactase activity little information is availalbe as to the age at which the lactase decreases. We attempted to determine a) the frequency of low intestinal lactase activity and b) the age at which the change occurs. For this purpose we reviewed in a large number of intestinal biopsies both histologically as well as for disaccharidase activities. The biopsies were obtained from a heterogeneous group of Caucasians, including patients, their siblings and parents. The patients were those with failure to thrive in whom no organic cause could be elicited, and those with the irritable colon syndrome. Patients ranged in age from 6 weeks to 50 years and out of a total of 1, 077 jejunal biopsies, 172 morphologically normal biopsies were selected. The milk drinking habits of 118 subjects and their families were elicited and 31 oral lactose tolerance tests performed. The mucosal lactase activity and sucrase-to-lactase ratio in those 172 individuals were plotted against age. In the first 3 years the mean lactase activity was 32.1 plus or minus 10.1 mumoles/g protein per min and the sucrase-to-lactase ratio was 1.7 plus or minus 0.5 with no change from year to year. However, after age 5 two separate groups emerge. A small group (24.6% of the population) with low lactase activity, and a second group possessing the same mean value for lactase activity as noted in the first 3 years. The low lactase activity group included children and adults with clinical lactose intolerance. These individuals consumed relatively small amounts of milk and when 12 of them were tested with an oral lactose tolerance test the result was a "flat" curve with a maximum rise in blood glucose of 9 plus or minus 3.2 mg/100 ml. The second group consumed more milk averaging 1 quart/day with no discomfort and when 19 were tested with oral lactose tolerance tests the values were normal. This study indicates that low lactase activity in the Caucasian population may make its appearance at the age of 5 years.

Adolescent↗
PubMed1992

Lactase gene expression during early development of rat small intestine.

Expression of lactase messenger (m) RNA and protein in rat small intestine during fetal and postnatal development was analyzed using in situ hybridization and immunohistochemistry. Lactase mRNA was first identified at 18 days of development, and lactase protein was first detected at day 20. Lactase mRNA and protein were present along the entire villus. Lactase mRNA increased, reaching a maximum at day 20. Just before birth a decrease in lactase mRNA was observed. In newborn intestine, lactase mRNA was present only from the base of the villus up to the mid-villus region and was undetectable up to the villus tips. Lactase protein continued to be expressed along the entire villus. These data show that expression of lactase mRNA and protein do not parallel, indicating a posttranscriptional control in fetal development. Lactase gene transcription is initiated late in gestation concomitant with villus formation and is exclusively seen in villus epithelial cells. The restriction after birth of lactase mRNA expression to cells at the villus base suggests the occurrence of a previously unknown step in postnatal differentiation of the enterocyte.

Age Factors↗
PubMed1991

Intestinal lactase expression and epithelial cell transit in hormone-treated suckling rats.

Cortisone- and/or thyroxine (T4)-induced changes in jejunal lactase activity and epithelial cell migration were studied to determine the relationship of these two events. In suckling rats given a single dose of cortisone on day 6, jejunal lactase activity increased by 37% and cell turnover rate by 95% 3 days later, whereas T4 alone induced no changes. After cortisone plus T4, jejunal lactase activity decreased by 23% while cell turnover rate increased by 176%. Among all animal groups, the patterns of lactase expression along the crypt-villus (C-V) axis were similar, being low at the C-V junction, increasing to a high plateau at the mid- or third quarter villus level, and decreasing slightly at the villus tip. The calculated epithelial cell age at half maximum lactase expression in cortisone-treated and cortisone plus T4-treated rats was 30 and 53% younger than in control rats. Maximum lactase activity in villus cells was approximately 45% higher in cortisone-treated than in control or cortisone plus T4-treated rats. Parallel measurements of sucrase and lactase activities along C-V axis showed elevated lactase activity at higher villus positions than lead sucrase activity, suggesting that cortisone action occurs in villus cells. Thus jejunal lactase expression may be modulated by 1) adjusting villus cell age required for maximum expression, 2) altering the level of lactase activity in villus cells, and 3) changing the turnover rate of lactase containing epithelial cells.

Aging↗
PubMed1977

Lactase deficiency: a common genetic trait of the American Indian.

Intestinal lactase activity was assessed indirectly in 156 American Indians by measuring breath hydrogen after an oral lactose load. Lactase deficiency was present in 66% of subjects and correlated highly with the percentage of Indian blood. Lactase deficiency was present by the age of 5 years and was unrelated to sex. Most lactase-deficient subjects (81%), but only a minority (23%) of lactase-sufficient subjects, developed symptoms after the oral lactose load, and among lactase-deficient subjects, symptoms occurred more frequently in adults than in children (P = 0.05). Indeed, by history, 53% of lactase-deficient adults, but only 10% of lactase-deficient children under 18 years of age, were aware of milk intolerance. Despite these differences, milk consumption was only slightly less (19 g) in the lactase-deficient subjects than in those with normal lactase activity (25 g) (P less than 0.05). The results indicate that lactase deficiency is a common autosomal genetic trait in the American Indian that becomes manifest in early childhood. Tolerance to dietary lactose appears to decline in the American Indian as he reaches adulthood, but in this population the decline in tolerance had only minor influence on lactose intake.

Adolescent↗
PubMed1977

Family studies of lactase deficiency in the American Indian.

To determine the pattern of inheritance of lactase deficiency, we studied 104 American Indian and 2 white subjects in 19 families. Subjects were considered deficient in lactase if breath-hydrogen excretion exceeded 0.20 ml per min above fasting at 2 hr after a lactose load of 2 g per kg of body weight (maximum 50 g). Seventy-one per cent of the males and 75% of the females were lactase deficient. In three families in which both parents were lactase normal, 40% of the children were lactase deficient; and in the three families with one parent lactase normal and the other lactase deficient, 65% of the children were deficient in lactase; and finally, in the seven families with both parents lactase deficient, 93% of the children were lactase deficient. This distribution of lactase deficiency in the families suggests that this trait shows an autosomal-recessive pattern of inheritance.

Adolescent↗
PubMed1991

Lactose intolerance and the genetic regulation of intestinal lactase-phlorizin hydrolase.

Lactase-phlorizin hydrolase, which hydrolyzes lactose, the major carbohydrate in milk, plays a critical role in the nutrition of the mammalian neonate. Lactose intolerance in adult humans is common, usually due to low levels of small intestinal lactase. Low lactase levels result from either intestinal injury or (in the majority of the world's adult population) alterations in the genetic expression of lactase. Although the mechanism of decreased lactase levels has been the subject of intensive investigation, no consensus has yet emerged. Recent studies have begun to define the cellular and molecular biology of this enzyme. In animals and humans, a glycosylated precursor is proteolytically cleaved to yield the mature enzyme on the microvillus membrane of the enterocyte, bound to the lipid bilayer only by a hydrophobic anchor sequence. The enzyme hydrolyzes lactose, phlorizin, and glycosylceramides. A decline in lactase specific activity occurs at the time of weaning in most mammalian species; in most humans who have low lactase activity as adults, the decline occurs at approximately 3-5 years of age. In a few human groups, the elevated juvenile level of lactase specific activity persists throughout adulthood. These developmental patterns of lactase expression are most likely regulated at the level of gene transcription.

Animals↗