Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine whether the developmental decline in lactase specific activity (mumol/min/g protein) in the rat was associated with (a) changes in the relative quantities of immunoisolated precursor and mature forms of the enzyme purified by SDS-PAGE and/or (b) immunohistologic changes in the jejunal mucosa. We studied 10- and 16-day-old suckling rat pups, 22-day-old weaned rat pups, and adult female rats (nongravid, pregnant, and lactating). Lactase activity was three- to fourfold higher in 10-day-old pups than in adult rats. Lactase activity was 27% greater in lactating compared with nongravid or pregnant rats. Three molecular forms of the enzyme that migrated identically in all animals were observed on SDS-polyacrylamide gels stained with Coomassie blue: 140-kDa (mature brush border form), 200-kDa, and 220-kDa (apparent precursor forms). There was a striking difference in the proportions of the three polypeptides at different ages that was unrelated to animal status, i.e., pregnant or lactating. As the animals aged, the relative amount of the 140-kDa band declined from 86 +/- 1.1% of the total immunoprecipitated lactase in 10-day old suckling pups to 68 +/- 0.7% in adults. Simultaneously, the relative concentration of the 200-kDa band rose from 1.7 +/- 0.4% in the 10-day-old to 19 +/- 0.6% in adults. The relative concentration of the 220-kDa polypeptide did not change as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Developmental changes in lactase-phlorizin hydrolase precursor isoforms in the rat. 143 63

Lactase is synthesized as a high-mannose large precursor (200 kDa) which is subsequently complex-glycosylated (215 kDa) and split into the 150 kDa mature form. The regulatory mechanisms responsible for the decline of activity at weaning are not yet known. We have set up in vitro cultures of intestinal mucosa from suckling and adult rabbit and found that suckling and adult animals synthesize the same four forms of lactase-phlorizin hydrolase (LPH) but with a different distribution. In the proximal adult small intestine there is very little 180 kDa form, which is most probably a product of the 215 kDa complex-glycosylated precursor. The 180 kDa form comprises a greater percentage of total LPH in the middle of the small intestine in adult and particularly in suckling rabbits. In the latter tissue this form is apparently more stable than in the adult tissue. Posttranscriptional control of lactase synthesis is therefore different in the various parts of the adult small intestine, and it is different in the suckling as compared to adult tissue.
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PMID:In vitro biosynthesis of lactase in preweaning and adult rabbit. 144 46

We determined along the small intestine of young and adult rabbits the activities of lactase (LPH) and sucrase (SI), the levels of their cognate mRNAs, and examined the in vitro biosynthesis of LPH and pro-SI. Lactase activity is low in the proximal 1/3 of the intestine, whereas the mRNA levels are high. However, the rates of biosynthesis of the LPH forms correlated well with the steady-state levels of LPH mRNA in all segments, indicating that factor(s) acting post-translationally produce a decline in brush border LPH in the proximal small intestine. These factor(s) are not involved in the processing of pro-LPH to mature LPH, since the relative amounts of the various forms of LPH are almost the same along the small intestine. Unexpectedly, we find that also for SI the ratio of activity to mRNA is low in proximal intestine. The biosynthesis of pro-SI correlates with the steady-state levels of its mRNA. Hence, the steady-state levels of LPH and SI along the small intestine are regulated both by mRNA levels and by posttranslational factor(s).
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PMID:The levels of lactase and of sucrase-isomaltase along the rabbit small intestine are regulated both at the mRNA level and post-translationally. 144 47

The evidence indicating a mucosal source for the jejunal fluid lactase activity of children is so far inconclusive. Samples of jejunal mucosa and the adjacent fluid were obtained simultaneously from 15 children. Lactase activity was measured at pH 5.9 in mucosa and fluid. Fluid activities showed a significant positive correlation with the activity of the corresponding mucosal homogenate but a stronger correlation was found with an enterocyte microvillous membrane fraction prepared from the same homogenate (r = 0.807 and 0.889, respectively). Kinetic and pH optima studies were consistent with a microvillous membrane origin. Fluid activity and pH optimum were not changed detectably when measured in the presence of an enterocyte lysosomal acid lactase inhibitor. Jejunal fluid lactase activity and its properties closely reflect the microvillous membrane enzyme. Lysosomal acid lactase does not contribute measurably to the total lactase activity of jejunal fluid.
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PMID:The nature of small bowel luminal fluid lactase. 181 57

Researchers do not understand what causes ovarian cancer. Some studies find galactose to be toxic to oocytes which renders ovaries susceptible to cancer. 1 hypothesis is that high levels of lactose consumption and retained ability to digest lactose (lactase persistence) lead to high levels of galactose exposure which increases the ovarian cancer risk. Denmark, Sweden, and Switzerland have the highest risk of ovarian cancer in the world. They also have the highest levels of lactase persistence and among the highest levels of milk supply for the population. Conversely, Hong Kong, Japan, Shanghai, and Singapore have low ovarian cancer risk, low consumption of milk, and low levels of lactase persistence. yet other researchers using the same data did not find per capita availability of milk to be significant independent of nondairy animal fat. Lactase persistence did have an independent association, however, but data was not standardized across populations. In a case control study, researchers took the dietary history of 11 dairy products to measure lactose consumption. A significant increase in ovarian cancer risk only existed with frequent intake of yogurt and cottage cheese. Researchers hypothesized that the prehydrolyzed lactose in both foods was the main contributor. Using the case control data, others found an increased risk for total lactose intake in women who never used oral contraceptives (OCs). The strongest predictor to date is the lactose/transferase ratio, yet those who found this association did not define this index based on an earlier study or examination. 1 problem with these studies is that dietary fat confounds the association. 2 studies showed that low fat milk was associated with decreased risk, even though both milks have the same lactose content. Another problem is that the subsets of exposure or subgroups of the population are unpredictable. Further research in nutritional epidemiology of ovarian cancer is needed.
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PMID:Invited commentary: progress in the nutritional epidemiology of ovary cancer. 189

Interactions of cortisone and thyroxine (T4) in modulating jejunal sucrase and lactase expression were studied in rats during early postnatal life. Cortisone (50 micrograms/g body wt) precociously induced sucrase activity in days 5-16 rats and enhanced activity thereafter until day 22. T4 (1 microgram/g) plus cortisone evoked greater sucrase expression in day 9 or younger rats. T4 did not induce sucrase expression until day 13. Lactase activity was enhanced in rats younger than day 9 by cortisone, and this effect was abolished when T4 was added. In days 19 and 22 rats, cortisone depressed lactase; with T4, lactase activity was further decreased. T4 alone did not suppress lactase activity until day 19. Quantitation of jejunal enzyme content showed that sucrase catalytic activity was higher in day 22 than 19 or younger rats and lower in rats given T4 than cortisone. In contrast, lactase activity remained constant in all animal groups. In vivo [35S]methionine-labeling studies using day 9 rats showed that cortisone induced de novo synthesis of sucrase and increased 35S incorporation into lactase. Cortisone plus T4 increased 35S incorporation into sucrase further and significantly increased 35S incorporation into lactase. We conclude that 1) cortisone and T4 cooperatively stimulate sucrase expression and reduce lactase activity during early postnatal life and 2) reduction in lactase activity accompanied by increase in lactase synthesis suggests that cortisone and T4 regulate lactase activity at posttranslational level.
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PMID:Thyroxine and cortisone cooperate to modulate postnatal intestinal enzyme differentiation in the rat. 190 Jun 72

Gastric intubation was adopted to examine the effect of continuous nutrient supply on digestive development of the pig during the immediate post-weaning period. The 14 d-weaned animals were slaughtered at 3, 5 and 7 d post-weaning (3W, 5W and 7W respectively) and the suckled animals were slaughtered at 14 and 22 d of age (14SR and 22SR respectively). The weight of the pancreas (g/kg bodyweight) was significantly greater (P less than 0.05) in the 5W and 7W groups, as was the weight of large intestine (g/kg) in all weaned groups (P less than 0.01) compared with sow-reared pigs. The stomach weight (g/kg) tended to be greater in the weaned groups. Weaning, in conjunction with a continuous nutrient supply, did not significantly alter the time-related changes in the weight of the small intestine (SI) or the SI mucosa, although both variables tended to be lowest in the 3W group. However, there was a 20% reduction in the protein content of the mucosa within the first 3 d post-weaning (P less than 0.01) which persisted during the 7 d experimental period. Lactase, (beta-galactosidase; EC 3.2.1.23) activity (mumol/g protein and mol/d) of the 7W group was reduced to approximately 40% of the 22SR value. Hence, continuous nutrient supply may have delayed, but did not prevent, the loss of lactase activity at weaning. The activity of sucrase (sucrose-alpha-glucosidase; EC 3.2.1.48) was significantly higher in 22SR compared with 14SR animals. Sucrase activity in weaned pigs was intermediate to the values for sow-reared pigs whereas maltase (alpha-glucosidase; EC 3.2.1.20) and glucoamylase (glucan 1,4-alpha-glucosidase; EC 3.2.1.3) were significantly increased in relation to their sow-reared counterparts. Continuous nutrient supply did not prevent the reduction in villous height and the crypt hypertrophy associated with weaning. The results of the present study suggest that there may be some degree of interaction between nutrient intake and gut development during the immediate post-weaning period but that there is also a component of the adaptive response which is independent of nutrient intake. They confirm the rapid substrate induction of the brush-border glucoamylases and indicate the importance of considering total as well as specific enzyme activity for satisfactory interpretation of changes in digestive function.
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PMID:Digestive development of the early-weaned pig. 1. Effect of continuous nutrient supply on the development of the digestive tract and on changes in digestive enzyme activity during the first week post-weaning. 190 70

The relationship between intestinal morphology, disaccharidase activity, and disaccharide absorption is controversial. A retrospective study of 798 consecutive biopsies was performed to determine whether disaccharidase activities varied by subject age, biopsy technique, and degree of villus atrophy. Lactase activity was inversely correlated with age in the absence or presence of villus atrophy; sucrase, maltase, and palatinase activities did not correlate with age. Biopsies obtained by capsule or endoscopy had similar disaccharidase activities. In subjects 24 months of age or younger, the degree of mucosal injury was inversely correlated with lactase activity. In subjects older than 24 months, the degree of mucosal injury was inversely correlated with maltase and, to a lesser extent, lactase activities. The data suggest that disaccharidase activities in mucosal biopsies, whether obtained by endoscopy or capsule, are diminished in the presence of mucosal injury and correlate inversely with the degree of injury.
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PMID:Human intestinal disaccharidase activities: correlations with age, biopsy technique, and degree of villus atrophy. 161 46

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.
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PMID:Posttranslational cleavage of rat intestinal lactase occurs at the luminal side of the brush border membrane. 190 27

The purpose of this study was to evaluate the effect of withdrawal of lactose from the diet for 72 hours on lactase activity in the jejunal mucosa of conventionally raised calves. The descending portion of the duodenum of six Holstein calves less than 24 hours old was cannulated. The calves were fed milk except on days 5, 6 and 7 when they were given the same volume of an electrolyte solution. Sequential biopsy specimens of the proximal jejunal mucosa were obtained for three weeks and the lactase activity determined. Lactase activity was highest on day 1 and a trend toward decreased lactase activity from birth until three weeks was observed. Mean lactase activity was significantly (p less than 0.05) higher for days 1, and 3 compared to days 9, 13 and 17. The withdrawal of milk and replacement by an electrolyte solution during three days had no significant effect on jejunal mucosal lactase activity in neonatal calves.
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PMID:Jejunal mucosal lactase activity from birth to three weeks in conventionally raised calves fed an electrolyte solution on days 5, 6 and 7 instead of milk. 190 7


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