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

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

In this review, the relationship between lactose and human cataract is examined from the presently available biochemical, metabolic, and epidemiological data. The exceptional cases of homozygous enzyme deficiency being excluded, fragmentary data give reason to believe that a risk of cataract secondary to lactose and galactose ingestion is present in certain subpopulations. In these population groups, the size of which is unknown, the lens could be exposed to intermittent episodes of hypergalactosemia due to the presence of a partial enzyme deficiency in the galactose metabolic pathway, and/or the persistence of a high adult jejunal lactase activity, and/or to a large and repeated consumption of either whole lactose or easily absorbed lactose (hydrolyzed forms and nonpasteurized yogurt).
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PMID:Lactose and cataract in humans: a review. 190 25

The present work investigates the ability of galactose to affect enterocyte differentiation during normal development in vivo. Energy intake has also been varied to take account of the fact that galactose is poorly metabolized in mice. Brush-border lactase, alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N, alkaline phosphatase and microvillus length were measured as markers of enterocyte differentiation in mice fed diets containing galactose (G diet), corn oil (E diet) or galactose + corn oil (G + E diet). Maintaining mice on a G instead of E diet reduced brush-border lactase activity and enterocyte migration rates; alpha-glucosidase, dipeptidylpeptidase-IV, aminopeptidase N and microvillus length expression increased and alkaline phosphatase activity remained unchanged. Feeding the G + E diet restored enterocyte migration rates, lactase, aminopeptidase N and dipeptidylpeptidase-IV activities to values found in mice fed the E diet. Galactose stimulation of alpha-glucosidase and microvillus length expression was, however, fully maintained in mice fed the G + E diet. Present results show that enterocyte differentiation is affected independently by varying dietary galactose and energy levels; that galactose effects always increase and energy effects usually decrease expression of enterocyte components and that energy stimulation of lactase activity is exceptional.
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PMID:Galactose effects on enterocyte differentiation in the mouse jejunum. 190 92

Oral administration of embelin (75 mg/kg per day, daily for 15 and 30 days) to male rats caused significant elevation in the uptake of D-glucose, L-alanine, L-leucine and calcium in small intestinal segments. Embelin also produced significant increases in intestinal brush border membrane-associated enzymes (sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase) in both intestinal homogenates and partially purified brush border membrane preparations. Significant increases were also noted for microsomal glucose-6-phosphatase and cytosolic lactate dehydrogenase. Increase in brush border membrane-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids and ganglioside sialic acid were seen but not in the cholesterol/phospholipid molar ratio. All these changes returned to control or near control levels following withdrawal of the drug.
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PMID:Effects of embelin, a male antifertility agent, on absorptive and digestive functions of rat intestine. 192 15

In vitamin A-deficient children, increased rates of bacterial infections in the intestine have been observed. The adherence of bacteria is a prerequisite for invasion. Thus, the effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes was studied. Male weanling rats matched by weight were divided into three groups: one group was fed a vitamin A-free diet for 8-12 weeks; another was given the same diet supplemented with retinol acetate; a third group matched for age served as controls. The vitamin A-deficient group showed a significantly lower growth rate and lower serum retinol levels than either the retinol acetate-supplemented or control groups. In all the groups, S. typhimurium possessing mannose-sensitive fimbriae adhered to enterocytes in significantly larger numbers than the nonfimbriated strains. The number of fimbriated S. typhimurium bound to enterocytes from the proximal small intestine was significantly higher in the vitamin A-deficient rats than in the pair-fed vitamin A-supplemented group (19.3 +/- 14.9 versus 7.8 +/- 5.0; p less than 0.05) or the control group (19.3 +/- 14.9 versus 8.7 +/- 3.5, p = 0.01). The specific activities of the enterocytes lactase, sucrase, and maltase and the protein content in the vitamin A-deficient rats were similar to those in the controls. These results demonstrate that vitamin A deficiency in rats is associated with the increased ability of S. typhimurium to adhere to proximal small intestinal enterocytes. However, the possible changes in the membrane of the enterocyte do not include decreases in brush border disaccharidases or protein content.
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PMID:Effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes. 197 42

The purpose of this investigation was to determine if the presence of carbohydrate in milk, either lactose or its hydrolysis products, enhance the bioavailability of calcium (Ca) in milk. Two studies were performed. In study A, fractional Ca absorption was measured in 11 lactose-tolerant postmenopausal women after an oral dose of 47Ca-equilibrated milk formula containing no carbohydrate (NOCHO), lactose (LACTOSE), or an equivalent amount of glucose plus galactose (SUGAR); all participated in three absorption studies in random order. The NOCHO formula contained 10.0 g protein and 217 mg Ca from a combination of milk mineral and protein isolates; the LACTOSE and SUGAR formulae contained in addition 12 g lactose or 6 g glucose plus 6 g galactose, respectively. In study B, fractional Ca absorption was measured in five postmenopausal women after an oral dose of 47Ca-equilibrated skim milk (217 mg Ca) and lactase-treated milk, each with sufficient carbohydrate added to equal 12 g. For both studies, the increase in forearm radioactivity 4 and 8 hours after oral 47Ca administration relative to the increase observed after IV administration was used to estimate fractional Ca absorption. The addition of lactose but not glucose plus galactose to the NOCHO formula enhanced Ca absorption (p less than 0.05). Fractional absorption at 4 hours was 0.386 from the LACTOSE formula compared with 0.310 for both the NOCHO and SUGAR formulae. Those individuals with the lowest absorption in the absence of carbohydrate had the greatest increase with lactose. In contrast, Ca absorption was the same from skim milk as from lactase-treated skim milk (study B).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of carbohydrates in milk on the absorption of calcium by postmenopausal women. 203 Feb 55

Present work uses a combination of quantitative cytochemistry and measurements of cell migration rates to describe galactose effects on lactase expression by mouse enterocytes. Mice fed galactose were found to eat less, weigh less and drink more than mice maintained on a low-carbohydrate isocalorific diet. The enterocyte migration rate in these mice was also only one third of that determined in low-carbohydrate-fed animals. The rate at which lactase activity increased in the brush border membrane of migrating enterocytes was 3-times greater in low-carbohydrate- compared with galactose-fed mice. The time during which this increase persisted was, however, 3-times less in low-carbohydrate-fed animals. The maximum rate of sucrase-maltase appearance, measured as control in these experiments, remained unaffected by galactose feeding. Galactose effects on lactase expression might in part result from mice being unable to metabolise this substrate. Previously it has been stated that galactose increases lactase biosynthesis in rat intestine (Koldovsky, O., Bustamonte, S. and Yamada (1981) In Mechanisms of intestinal adaptation (Robinson, J.W.L., Dowling, R.H. and Ricken, E.O., eds.), pp. 153-156, MTP Press, Lancaster). This result is discussed in relation to the opposite finding reported in the present work for mouse jejunal enterocytes. The need to relate enzyme appearance to age and developmental state of enterocytes in this type of study is also emphasized.
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PMID:Galactose inhibits lactase expression by mouse jejunal enterocytes. 210 3

Age-specific changes in glycosylation of rat intestinal lactase-phlorizin hydrolase were analyzed using enzyme immunoprecipitated from microvillus membranes of suckling, weaning, and adult rats, and carbohydrate moieties were examined by lectin affinity binding, metabolic labeling, and neuraminidase treatment. Lectin binding indicated the presence of N-linked and O-linked oligosaccharide chains containing mannose and galactose throughout development. An age-dependent shift in sialic acid and fucose was seen during the period of weaning; no fucose was detectable in lactase-phlorizin hydrolase until after the rats were 20 days of age, whereas sialic acid was reduced in adult lactase-phlorizin hydrolase. The presence of sialic acid in suckling intestines and fucose in adult was confirmed by metabolic labeling with appropriate radioactive precursors. Sodium dodecyl phosphate-polyacrylamide gel electrophoresis analysis of immunoprecipitated lactase-phlorizin hydrolase from the proximal and mid small intestine showed two bands of approximately 220 and 130 kilodaltons in all age groups. In the distal part of the adult small intestine, lactase-phlorizin hydrolase appeared as two bands of similar size to those found in the proximal and mid portions. In contrast, during the suckling and weaning periods, these distal bands were approximately 225 and 135 kilodaltons. [35S]-methionine labeling and fluorography of neonatal intestines confirmed these observations. The size difference between proximal and distal small intestines was virtually eliminated by neuraminidase treatment. These data indicate that the core structure of microvillus membrane lactase-phlorizin hydrolase, consisting of both N-linked and O-linked oligosaccharides, remains constant during development, although terminal sugars shift from predominantly sialic acid during the suckling period to fucose in adulthood. This alteration in glycosylation of the protein occurs in a different pattern from the postweaning decline in lactase specific activity. Consequently, age-dependent changes in glycosylation cannot account for the decrease in lactase-phlorizin hydrolase-specific activity observed during development.
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PMID:Glycosylation of lactase-phlorizin hydrolase in rat small intestine during development. 210 55

Administration of Embelin, an experimental antifertility agent, to male rats (20 mg/kg body wt/day, daily for 15 and 30 days), caused an elevation in the uptake of D-glucose, L-alanine, L-leucine, and calcium in the small intestinal segments. An increase was also noted in the intestinal brush border membrane (BBM)-associated enzymes, sucrase, lactase, maltase, alkaline phosphatase, and leucine aminopeptidase in both the intestinal homogenates and partially purified BBM preparations, particularly after 30-day administration of the drug. Embelin treatment also caused a significant increase in the microsomal glucose-6-phosphatase and the cytosolic enzyme, lactate dehydrogenase. In the Embelin-treated animals BBM-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids, ganglioside-sialic acids as well as the cholesterol/phospholipids molar ratio showed a considerable increase. All these changes in the Embelin-treated animals were restored back to the normal or near normal biochemical makeup when the drug therapy was withdrawn and the animals were allowed to recover for another 15 and 30 days, respectively.
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PMID:Changes in glucose/amino acid/calcium uptake and brush-border membrane-associated enzymes in rat small intestine after the administration of embelin (plant benzoquinone), an antifertility agent. 211 47

The intestinal brush-border enzyme lactase splits lactose into its component monosaccharides, glucose and galactose. Relative deficiency of the enzyme during adulthood is a common condition worldwide and is frequently associated with symptoms of lactose intolerance. We studied the synthesis and processing of lactase in normal and adult hypolactasic subjects using human intestinal explants in organ culture. Metabolic labeling experiments in our control subjects with [35S]methionine followed by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, and fluorography demonstrated that newly synthesized lactase is initially recognized as a precursor molecule with a relative molecular weight (Mr) of 205,000. Over the course of several hours most of the labeled lactase was converted to a mature form of 150,000 Mr. Transiently appearing forms of 215,000 and 190,000 Mr were identified and were felt to represent intermediary species generated during intracellular processing. We identified two distinct alterations in lactase biosynthesis accounting for adult hypolactasia. Studies in three deficient subjects demonstrated markedly reduced synthesis of the precursor protein though posttranslational processing appeared identical to normal. Multiple studies in a fourth deficient subject demonstrated synthesis of ample amounts of precursor lactase but reduced conversion to the mature active form of the enzyme.
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PMID:The biosynthetic basis of adult lactase deficiency. 212 Feb 87


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