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)

This study describes the intracellular compartmentalization of three different mRNAs in the polarized rat fetal enterocyte. They encode proteins that are known to be localized within different regions of the epithelial cell namely (i) the apical, membrane-bound glycoprotein, lactase-phlorizin hydrolase (lactase), (ii) the mitochondrially localized enzyme, carbamoylphosphate synthetase (CPS), and (iii) the cytoplasmically localized enzyme, phosphoenolpyruvate carboxykinase (PEPCK). These mRNAs are found in close proximity to their respective protein products, i.e. the apical membrane, mitochondria and cytoplasm, respectively. The significance of these observations is twofold; (i) they indicate that mRNAs are sorted into specific domains of the cytosol of intestinal epithelial cells; and (ii) they imply the presence of two distinct pathways of mRNA targeting one that allows transport of mRNAs that are translated on ribosomes associated with the rough endoplasmic reticulum (lactase mRNA), and the other that allows sorting of mRNAs that are translated on free polysomes (CPS and PEPCK mRNA).
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PMID:Messenger RNA sorting in enterocytes. Co-localization with encoded proteins. 156 19

In the rat, starvation lowers jejunal sucrase activity and increases or has no effect upon jejunal lactase activity. The mechanism by which starvation influences these intrinsic microvillus proteins remains unclear. Jejunal sucrase and lactase activities were studied during starvation or refeeding after a three-day fast. Using polyclonal monospecific antibodies, sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH) protein contents were measured in parallel to determine changes in enzyme activation. Sucrase activity and SI protein fell after two and three days of fasting and rose during refeeding. In contrast, lactase activity and jejunal LPH content increased after starvation and decreased after refeeding for 48 hr. For both enzymes, changes in catalytic activity and protein content occurred in parallel. [3H]Leucine incorporation studies in vivo showed more labeling of immunoprecipitable LPH than SI during starvation, but refeeding induced relatively more labeling of SI than of LPH. Therefore, starvation and refeeding produce opposing effects upon jejunal lactase and sucrase activities by modulating LPH and SI protein production and not by modifying enzyme activation.
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PMID:Effects of starvation and refeeding on jejunal disaccharidase activity. 158 86

At weaning, the lactase-phlorizin hydrolase (LPH) mRNA was shown to disappear specifically from the distal part of ileum while remaining abundant in the more proximal segments of the small intestine. The purpose of this study was to analyze the longitudinal distribution of this transcript in rats whose intestinal lumen content was modified before and after weaning. Preweaned animals force-fed with an artificial diet retained a high amount of LPH mRNA in the jejunum, whereas this transcript precociously decreased in the distal ileum. Conversely, prolonged nursing delayed the specific decay of the LPH mRNA in the latter segment. Food deprivation in preweaned animals did not alter the longitudinal distribution of this transcript in that it remained abundant in the distal ileum. In adult rats, rearranging the order of the small intestinal segments with regard to the intraluminal flow of nutrients did not modify the typical distribution of the LPH mRNA. These results suggest that switching over from milk to the adult-type diet at weaning contributes to the modification of the longitudinal distribution of the LPH mRNA that normally occurs at this stage. However, once the adult pattern of expression of this transcript is established, it cannot be significantly altered by changing the position of each intestinal segment as well as its luminal content.
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PMID:Dietary control of the lactase mRNA distribution along the rat small intestine. 161 44

Intracellular processing of human intestinal lactase-phlorizin hydrolase (LPH) includes an essential proteolytic cleavage step that generates the mature brush border enzyme from the single-chain polypeptide precursor (pro-LPH). Previous work in organ culture of small intestinal biopsy samples [Naim, Sterchi & Lentze (1987) Biochem. J. 241, 427-434] has demonstrated that this cleavage occurs intracellularly. Since no intermediate forms of pro-LPH (trimmed or complex glycosylated) could be discerned in pulse-chase analyses it was suggested that the cleavage process occurs at a fast rate. To identify intermediate forms of pro-LPH prior to cleavage, I studied the biosynthesis of LPH by employing a pulse-chase protocol in mucosa explants (or biopsies) at reduced temperatures (22 degrees C). Here, I could identify by immunoprecipitation with monoclonal anti-LPH antibodies four LPH forms that exhibited a product-precursor relationship:mannose-rich precursor (pro-LPHh), trimmed pro-LPH (LPHt), complex glycosylated pro-LPH (pro-LPHc) and cleaved, mature LPH (LPHm). The results clearly indicate that the generation of mature LPH is preceded by complex glycosylation of the precursor form. The fact that this was not previously observed in the same experimental system under normal biosynthetic labelling conditions (37 degrees C) demonstrates that the cleavage process of pro-LPH occurs at a fast rate in the human small intestine.
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PMID:Processing of human pro-lactase-phlorizin hydrolase at reduced temperatures: cleavage is preceded by complex glycosylation. 163 91

Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine.
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PMID:Regulation of intestinal lactase in adult hypolactasia. 173 43

The principal carbohydrate of human milk is the disaccharide lactose. In human and all mammalian species, lactose is hydrolyzed in the small intestine by lactase-phlorizin hydrolase, also abbreviated as lactase. The absence of lactase results in the passage of undigested lactose into the large intestine and is associated with a well-known clinical syndrome: lactose intolerance. Low lactase levels result either from intestinal injury or, as in the majority of world's adult population, from alterations in the genetic expression of lactase. In this review terminology, pathophysiology, symptoms, diagnostic procedures, and therapy of lactose intolerance will be discussed.
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PMID:Clinical aspects of lactose intolerance in children and adults. 177 44

Enterocytes of the intestinal mucosa of infant and adult rats continuously proliferate in the crypt, mature as they migrate along the villus column, and are discharged from the villus tip. We examined the synthesis patterns of total protein, lactase-phlorizin hydrolase, sucrase-isomaltase, and maltase-glucoamylase as well as the accumulation of these enzymes in cells during migration along the villus. Labeled leucine was administered intraperitoneally to suckling and young adult rats, and radioactivity was determined in protein and digestive carbohydrase pools of developing villus cells separated sequentially from tip to base of the villus column. The developing cells were found to continuously accumulate protein and carbohydrates as they ascended the villus column. In addition, incorporation of radioactivity into total protein and carbohydrase pools occurred at generally constant rates along the length of the villus. These studies showed that the differentiated enterocyte of both infant and young adult rat intestine exhibits a pattern of continuous growth while migrating the length of the villus column and maintains synthesis of protein and digestive carbohydrates at generally constant rates during this time.
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PMID:Synthesis and accumulation of protein and carbohydrases along the rat villus column. 179 99

Laminaribiose and gentiobiose, two O-beta-linked disaccharides deriving from plant beta-glucans, were found to be hydrolyzed in the rat small intestine by an enzyme anchored into the brush border membrane of the enterocytes. Immunological and biochemical data, together with the developmental pattern of expression, support that this activity is carried out by the bifunctional enzyme involved in the hydrolysis of lactose and glycosylceramides: the lactase-phlorizin hydrolase complex.
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PMID:Derivatives of plant beta-glucans are hydrolyzed by intestinal lactase-phlorizin hydrolase of mammals. 180 69

This study shows the distribution of the messenger RNA for lactase-phlorizin hydrolase during postnatal development and along the longitudinal axis of the rat small intestine. At birth, this messenger RNA was present along the whole length of small intestine, and its concentration remained elevated during the suckling period despite the concomitant decrease in enzyme activity. At weaning, the amount of lactase messenger RNA dropped specifically in the distal ileum. This decrease in lactase messenger RNA was initiated at the ileocecal junction, progressed gradually towards the jejunum, and followed the decrease in lactase activity several days later. Starvation and refeeding were also found to cause modifications of lactase activity and messenger RNA expression that were prominent in the distal part of small intestine. These data support that posttranscriptional and pretranslational levels of regulation are required to define the spatial and temporal expression of lactase in the rat small intestine.
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PMID:Lactase expression is controlled differently in the jejunum and ileum during development in rats. 189 50

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.
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PMID:Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase. 190 57


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