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)

The synthesis and secretion of apolipoprotein B (apo B) was studied in a human colon carcinoma (Caco-2) cell line and in explants from normal human intestine. In Caco-2 cells, the specific activity of the intestinal disaccharidases maltase, sucrase-isomaltase and lactase was enhanced 8-, 6- and 3-fold respectively, at 19 days post-confluence as compared with 1-day-post-confluence cultures. The level of apo B secreted into the medium increased from undetectable in the cells just reaching confluency, to 115 ng/ml at 18 days post-confluence. The presence of apo B-100 and apo B-48 with mobilities on SDS/polyacrylamide-gel electrophoresis corresponding to those of human very-low-density lipoproteins and lymph chylomicrons, respectively, was detected in the media from 7-, 12- and 18-days-post-confluence cells. These two apo B proteins were also found intracellularly in 7-day-post-confluence cultures. However, more differentiated cells (12 and 18 days post-confluence) accumulated large amount of a 214 kDa protein intracellularly. Apo B-related 214 kDa protein was also synthesized by normal human intestinal explants. A pulse-chase experiment with explants from normal human jejunum showed a slow intracellular conversion of the 214 kDa protein into the size of mature apo B-48 (264 kDa), concomitant with increasing amounts of mature apo B-48 in the medium, suggesting a precursor-product relationship. Despite large intracellular quantities, the 214 kDa protein from the normal human tissue and Caco-2 cells was absent from the medium. No apo B-100 synthesis was detected in the human explants. These findings may help in our understanding of cholesterol and lipid metabolism in health and in some disorders characterized by the inability to secrete apo B-containing lipoproteins.
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PMID:Biosynthetic precursor (214 kDa) of apolipoprotein B-48 is not secreted by Caco-2 cells and normal human intestine. 260 23

In rodents, there is a surge of intestinal expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) in the late fetal phase just before morphological maturation and the onset of expression of numerous epithelial genes. To investigate directly the hypothesis that C/EBPalpha plays a causal role in the latter phenomena, we have assessed both structural and functional maturation in neonatal intestine from C/EBPalpha-null mice and their littermates. No effects of C/EBPalpha genotype were observed on mucosal architecture or on the size of the proliferative zone in the intestinal crypts. Likewise, the mRNA levels for the glucose transporter 2 (GLUT2), intestinal and liver fatty acid-binding proteins, and apolipoprotein A-IV in newborn intestine were similar in all genotypes. Paradoxically, Na+/glucose co-transporter (SGLT1), lactase phlorizin-hydrolase and apolipoprotein B mRNAs were more abundant in the C/EBPalpha-deficient animals. In wild-type intestines, C/EBPbeta and C/EBPdelta mRNAs were detectable throughout the late fetal period and increased toward term in parallel with C/EBPalpha mRNA. In newborn intestine, there was no compensatory up-regulation of these isoforms in the C/EBPalpha-deficient mice. We conclude that C/EBPalpha has no essential role in morphological maturation of the intestine, the pattern of proliferation of the epithelium, or the onset of expression of this cluster of epithelial mRNAs. However, since other C/EBP isoforms are present in the developing intestine, it is possible that there is a generic requirement for a member of the C/EBP family.
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PMID:Intestinal maturation in mice lacking CCAAT/enhancer-binding protein alpha (C/EPBalpha). 949 81

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal fatty acid-binding protein polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or microsomal triglyceride transfer protein mass and activity. Similarly, the alanine to threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis.
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PMID:The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants. 1148 82