Sucrase-Isomaltase Complex
Sucrase
Oligo-1,6-Glucosidase
Disaccharidases
alpha-Glucosidases
Intestine, Small
Carbohydrate Metabolism, Inborn Errors
Jejunum
Pinnipedia
Shrews
Multienzyme Complexes
A strategy for enhancing the transcriptional activity of weak cell type-specific promoters. (1/157)
Cell type- and tissue-specific promoters play an important role in the development of site-selective vectors for gene therapy. A large number of highly specific promoters has been described, but their applicability is often hampered by their inefficient transcriptional activity. In this study, we describe a new strategy for enhancing the activity of weak promoters without loss of specificity. The basic principle of this strategy is to establish a positive feedback loop which is initiated by transcription from a cell type-specific promoter. This was achieved by using a cell type-specific promoter to drive the simultaneous expression of the desired effector/reporter gene product and a strong artificial transcriptional activator which stimulates transcription through appropriate binding sites in the promoter. Using a VP16-LexA chimeric transcription factor, we show that this approach leads to a 14- to > 100-fold enhancement of both the endothelial cell-specific von Willebrand factor promoter and the gastrointestinal-specific sucrase-isomaltase promoter while maintaining approximately 30- to > 100-fold cell type specificity. (+info)Immunological analysis of beta-thalassemic mouse intestinal proteins reveals up-regulation of sucrase-isomaltase in response to iron overload. (2/157)
Maintenance of iron homeostasis must balance the demand for iron due to heme synthesis, which is driven by hematopoiesis, and the restricted intestinal uptake of iron, which otherwise limits absorption of this toxic element. The consequences of perturbed iron homeostasis are witnessed in inherited forms of beta-thalassemia in which erythroid hyperplasia results in enhanced intestinal iron absorption despite tissue iron overload. To gain a better understanding of intestinal factors that are induced when iron homeostasis is disrupted, a panel of monoclonal antibodies that recognize intestinal microvillous membrane proteins of the beta-thalassemic Hbbd(th3)/Hbbd(th3) mouse was established. The monoclonal antibodies were screened by differential Western blotting against normal and beta-thalassemic mouse intestine to identify antigens modulated in the disease state. Here we report the initial characterization of one immunoreactive species that is up-regulated in beta-thalassemic mouse intestine and the tentative identification of this antigen as sucrase-isomaltase. Studies in Caco-2 cells revealed the rather unexpected finding that expression of this intestinal hydrolase is increased in response to iron toxicity. (+info)Sucrase-isomaltase and hexose transporter gene expressions are coordinately enhanced by dietary fructose in rat jejunum. (3/157)
We previously demonstrated that the levels of mRNAs of both sucrase-isomaltase (SI) and sodium/D-glucose transporter (SGLT1) are modulated by dietary sucrose in the rat jejunum. In the present study, we investigated whether the transcription of the gene coding SI is regulated by certain types of monosaccharides. Force-feeding a fructose and sucrose diet, (40% energy as fructose or sucrose) gave rise to parallel increases in the transcripts of SI and intestinal hexose transporters (SGLT1, GLUT5, and GLUT2) within 12 h. Force-feeding a glycerol-containing diet also caused an enhancement of SI, SGLT1, and GLUT2 mRNA levels. However, feeding the diet containing glucose or alpha-methylglucoside generally did not increase the transcript levels of SI or the intestinal hexose transporters. Nuclear run-on assays revealed that fructose as well as sucrose increased the transcription of both SI and GLUT5 genes and that the transcription rates of these genes were unaffected by glucose. These results suggest that fructose (or a metabolite) is capable of increasing the mRNA levels of SI and hexose transporters in the small intestine and that transcriptional regulation might play a pivotal role in the carbohydrate-induced coordinate enhancement of SI and fructose transporter gene expression (+info)Dissociation between growth arrest and differentiation in Caco-2 subclone expressing high levels of sucrase. (4/157)
Growth arrest and cell differentiation are generally considered temporally and functionally linked phenomena in small intestinal crypt cells and colon tumor cell lines (Caco-2, HT-29). We have derived a Caco-2 subclone (NGI3) that deviates from such a paradigm. In striking contrast with the parental cells, proliferative and subconfluent NGI3 cells were found to express sucrase-isomaltase (SI) mRNA and to synthesize relatively high levels of SI, dipeptidyl peptidase IV, and aminopeptidase N (APN). In postconfluent cells, little difference was seen in SI mRNA levels between Caco-2 and NGI3 cells, but the latter still expressed much higher levels of SI that could be attributed to higher rates of translation. APN expression was also greatly enhanced in NGI3 cells. To determine whether high levels of brush-border enzymes correlated with expression of cell-cycle regulatory proteins, we investigated their relative cellular levels in growing and growth-arrested cells. The results showed that the cyclin-dependent kinase inhibitors (p21 and p27) and D-type cyclins (D1 and D3) were all induced in postconfluent cells, but NGI3 cells expressed much higher levels of p21. This study demonstrated that cell growth and expression of differentiated traits are not mutually exclusive in intestinal epithelial cells and provided evidence indicating that posttranscriptional events play an important role in regulation of SI expression. (+info)Lactase-phlorizin hydrolase and sucrase-isomaltase genes are expressed differently along the villus-crypt axis of rat jejunum. (5/157)
Lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) are two disaccharidases specifically expressed in small intestinal absorptive cells. We previously showed that the transcripts of both genes are elevated within 12 h of carbohydrate intake. To examine at which locus of villus-crypt axis this response to dietary carbohydrate occurs, 6-wk-old rats were fed a low-carbohydrate diet (5% energy) for 7 d, and then force-fed either the low-carbohydrate diet or a sucrose (40% energy) diet during the last 6 h. Cryostat sectioning of jejunal segments followed by RNA blot hybridizations of the transcripts revealed that, unlike SI mRNA which was expressed maximally in the lower villus, maximal LPH mRNA level was attained at the upper villus. The distribution of the respective immunoreactive protein and the enzymatic activity was shifted more toward the villus tips for LPH than for SI. Force-feeding the sucrose diet caused an abrupt increase in SI mRNA level in the lower villus within 3 h, while the rise in LPH mRNA level occurred in the mid- and upper-villus. The diet-induced increases in the LPH mRNA and SI mRNA levels were abolished along the entire villus by the administration of actinomycin D. These results suggest that LPH gene is maximally expressed in more apical villus cells than SI gene, and that dietary sucrose elicits enhancement of the gene expressions in the villus cells which are accumulating the respective transcripts. (+info)O-linked glycans mediate apical sorting of human intestinal sucrase-isomaltase through association with lipid rafts. (6/157)
The plasma membrane of polarised epithelial cells is characterised by two structurally and functionally different domains, the apical and basolateral domains. These domains contain distinct protein and lipid constituents that are sorted by specific signals to the correct surface domain [1]. The best characterised apical sorting signal is that of glycophosphatidylinositol (GPI) membrane anchors [2], although N-linked glycans on some secreted proteins [3] and O-linked glycans [4] also function as apical sorting signals. In the latter cases, however, the underlying sorting mechanisms remain obscure. Here, we have analysed the role of O-glycosylation in the apical sorting of sucrase-isomaltase (SI), a highly polarised N- and O-glycosylated intestinal enzyme, and the mechanisms underlying this process. Inhibition of O-glycosylation by benzyl-N-acetyl-alpha-D-galactosaminide (benzyl-GalNAc) was accompanied by a dramatic shift in the sorting of SI from the apical membrane to both membranes. The sorting mechanism of SI involves its association with sphingolipid- and cholesterol-rich membrane rafts because this association was eliminated when O-glycosylation was inhibited by benzyl-GaINAc. The results demonstrate for the first time that O-linked glycans mediate apical sorting through association with lipid rafts. (+info)Temporal association of the N- and O-linked glycosylation events and their implication in the polarized sorting of intestinal brush border sucrase-isomaltase, aminopeptidase N, and dipeptidyl peptidase IV. (7/157)
The temporal association between O-glycosylation and processing of N-linked glycans in the Golgi apparatus as well as the implication of these events in the polarized sorting of three brush border proteins has been the subject of the current investigation. O-Glycosylation of pro-sucrase-isomaltase (pro-SI), aminopeptidase N (ApN), and dipeptidyl peptidase IV (DPPIV) is drastically reduced when processing of the mannose-rich N-linked glycans is blocked by deoxymannojirimycin, an inhibitor of the Golgi-located mannosidase I. By contrast, O-glycosylation is not affected in the presence of swainsonine, an inhibitor of Golgi mannosidase II. The results indicate that removal of the outermost mannose residues by mannosidase I from the mannose-rich N-linked glycans is required before O-glycosylation can ensue. On the other hand, subsequent mannose residues in the core chain impose no sterical constraints on the progression of O-glycosylation. Reduction or modification of N- and O-glycosylation do not affect the transport of pro-SI, ApN, or DPPIV to the cell surface per se. However, the polarized sorting of two of these proteins, pro-SI and DPPIV, to the apical membrane is substantially altered when O-glycans are not completely processed, while the sorting of ApN is not affected. The processing of N-linked glycans, on the other hand, has no influence on sorting of all three proteins. The results indicate that O-linked carbohydrates are at least a part of the sorting mechanism of pro-SI and DPPIV. The sorting of ApN implicates neither O-linked nor N-linked glycans and is driven most likely by carbohydrate-independent mechanisms. (+info)Glucocorticoids have pleiotropic effects on small intestinal crypt cells. (8/157)
Glucocorticoids have long been known to accelerate maturation of the intestinal tract, but the molecular mechanisms that account for their physiological function in the epithelium remain poorly characterized. Using rat intestinal epithelial cell lines (IEC-6, IEC-17, and IEC-18) as models, we have characterized glucocorticoid receptors in crypt cells and documented striking morphological, ultrastructural, and functional alterations induced by these hormones in intestinal cells. They include arrest of growth, formation of tight junctions, appearance of long, slender microvilli, reorganization of the endoplasmic reticulum and trans-Golgi network, and downregulation of the cell cycle regulatory proteins cyclin-dependent kinase 6 and p27(Kip1). These effects are consistent with the activation or modulation of multiple genes important in the physiological function of absorptive villous cells but are probably not directly involved in the induction of cell differentiation. (+info)The sucrase-isomaltase complex is a disaccharidase enzyme found on the brush border membrane of the small intestinal epithelial cells. This enzyme plays a crucial role in digesting carbohydrates, particularly sugars like sucrose (table sugar) and maltose (malt sugar), into simpler monosaccharides that can be absorbed by the body.
The sucrase-isomaltase complex is formed by two major enzymes: sucrase and isomaltase. Sucrase catalyzes the hydrolysis of sucrose into glucose and fructose, while isomaltase breaks down maltose and other related carbohydrates, such as maltotriose and higher-order α-limit dextrins, into glucose molecules.
Defects or deficiencies in the sucrase-isomaltase complex can lead to genetic disorders like congenital sucrase-isomaltase deficiency (CSID), which is characterized by impaired digestion and absorption of sugars, causing gastrointestinal symptoms such as bloating, diarrhea, and abdominal pain.
Sucrase is a digestive enzyme that is produced by the cells lining the small intestine. Its primary function is to break down sucrose, also known as table sugar or cane sugar, into its component monosaccharides: glucose and fructose. This process allows for the absorption of these simple sugars into the bloodstream, where they can be used as energy sources by the body's cells.
Sucrase is often deficient in people with certain genetic disorders, such as congenital sucrase-isomaltase deficiency (CSID), which leads to an impaired ability to digest sucrose and results in gastrointestinal symptoms like bloating, diarrhea, and abdominal pain after consuming sugary foods or beverages. In these cases, a sucralose-based diet may be recommended to alleviate the symptoms.
Oligo-1,6-glucosidase is an enzyme that breaks down complex carbohydrates by hydrolyzing the α-1,6 glycosidic bonds in oligosaccharides, producing simpler sugars such as glucose. This enzyme plays a crucial role in the digestion of certain types of carbohydrates, particularly those found in plants.
Deficiency or absence of this enzyme can lead to a rare genetic disorder called Glycogen Storage Disease Type IV (GSD IV), also known as Andersen's disease. This condition is characterized by the accumulation of abnormal glycogen molecules in various organs, leading to progressive damage and failure.
It's important to note that oligo-1,6-glucosidase should not be confused with other similar enzymes such as α-glucosidase or lactase, which have different functions and substrate specificities.
Disaccharidases are a group of enzymes found in the brush border of the small intestine. They play an essential role in digesting complex carbohydrates into simpler sugars, which can then be absorbed into the bloodstream. The three main disaccharidases are:
1. Maltase-glucoamylase: This enzyme breaks down maltose (a disaccharide formed from two glucose molecules) and maltotriose (a trisaccharide formed from three glucose molecules) into individual glucose units.
2. Sucrase: This enzyme is responsible for breaking down sucrose (table sugar, a disaccharide composed of one glucose and one fructose molecule) into its component monosaccharides, glucose and fructose.
3. Lactase: This enzyme breaks down lactose (a disaccharide formed from one glucose and one galactose molecule) into its component monosaccharides, glucose and galactose.
Deficiencies in these disaccharidases can lead to various digestive disorders, such as lactose intolerance (due to lactase deficiency), sucrase-isomaltase deficiency, or congenital sucrase-isomaltase deficiency (CSID). These conditions can cause symptoms like bloating, diarrhea, and abdominal cramps after consuming foods containing the specific disaccharide.
Alpha-glucosidases are a group of enzymes that break down complex carbohydrates into simpler sugars, such as glucose, by hydrolyzing the alpha-1,4 and alpha-1,6 glycosidic bonds in oligosaccharides, disaccharides, and polysaccharides. These enzymes are located on the brush border of the small intestine and play a crucial role in carbohydrate digestion and absorption.
Inhibitors of alpha-glucosidases, such as acarbose and miglitol, are used in the treatment of type 2 diabetes to slow down the digestion and absorption of carbohydrates, which helps to reduce postprandial glucose levels and improve glycemic control.
The small intestine is the portion of the gastrointestinal tract that extends from the pylorus of the stomach to the beginning of the large intestine (cecum). It plays a crucial role in the digestion and absorption of nutrients from food. The small intestine is divided into three parts: the duodenum, jejunum, and ileum.
1. Duodenum: This is the shortest and widest part of the small intestine, approximately 10 inches long. It receives chyme (partially digested food) from the stomach and begins the process of further digestion with the help of various enzymes and bile from the liver and pancreas.
2. Jejunum: The jejunum is the middle section, which measures about 8 feet in length. It has a large surface area due to the presence of circular folds (plicae circulares), finger-like projections called villi, and microvilli on the surface of the absorptive cells (enterocytes). These structures increase the intestinal surface area for efficient absorption of nutrients, electrolytes, and water.
3. Ileum: The ileum is the longest and final section of the small intestine, spanning about 12 feet. It continues the absorption process, mainly of vitamin B12, bile salts, and any remaining nutrients. At the end of the ileum, there is a valve called the ileocecal valve that prevents backflow of contents from the large intestine into the small intestine.
The primary function of the small intestine is to absorb the majority of nutrients, electrolytes, and water from ingested food. The mucosal lining of the small intestine contains numerous goblet cells that secrete mucus, which protects the epithelial surface and facilitates the movement of chyme through peristalsis. Additionally, the small intestine hosts a diverse community of microbiota, which contributes to various physiological functions, including digestion, immunity, and protection against pathogens.
Glucosidases are a group of enzymes that catalyze the hydrolysis of glycosidic bonds, specifically at the non-reducing end of an oligo- or poly saccharide, releasing a single sugar molecule, such as glucose. They play important roles in various biological processes, including digestion of carbohydrates and the breakdown of complex glycans in glycoproteins and glycolipids.
In the context of digestion, glucosidases are produced by the pancreas and intestinal brush border cells to help break down dietary polysaccharides (e.g., starch) into monosaccharides (glucose), which can then be absorbed by the body for energy production or storage.
There are several types of glucosidases, including:
1. α-Glucosidase: This enzyme is responsible for cleaving α-(1→4) and α-(1→6) glycosidic bonds in oligosaccharides and disaccharides, such as maltose, maltotriose, and isomaltose.
2. β-Glucosidase: This enzyme hydrolyzes β-(1→4) glycosidic bonds in cellobiose and other oligosaccharides derived from plant cell walls.
3. Lactase (β-Galactosidase): Although not a glucosidase itself, lactase is often included in this group because it hydrolyzes the β-(1→4) glycosidic bond between glucose and galactose in lactose, yielding free glucose and galactose.
Deficiencies or inhibition of these enzymes can lead to various medical conditions, such as congenital sucrase-isomaltase deficiency (an α-glucosidase deficiency), lactose intolerance (a lactase deficiency), and Gaucher's disease (a β-glucocerebrosidase deficiency).
Inborn errors of carbohydrate metabolism refer to genetic disorders that affect the body's ability to break down and process carbohydrates, which are sugars and starches that provide energy for the body. These disorders are caused by defects in enzymes or transport proteins that play a critical role in the metabolic pathways involved in carbohydrate metabolism.
There are several types of inborn errors of carbohydrate metabolism, including:
1. Galactosemia: This disorder affects the body's ability to metabolize the sugar galactose, which is found in milk and other dairy products. It is caused by a deficiency of the enzyme galactose-1-phosphate uridylyltransferase.
2. Glycogen storage diseases: These disorders affect the body's ability to store and break down glycogen, which is a complex carbohydrate that serves as a source of energy for the body. There are several types of glycogen storage diseases, each caused by a deficiency in a different enzyme involved in glycogen metabolism.
3. Hereditary fructose intolerance: This disorder affects the body's ability to metabolize the sugar fructose, which is found in fruits and sweeteners. It is caused by a deficiency of the enzyme aldolase B.
4. Pentose phosphate pathway disorders: These disorders affect the body's ability to metabolize certain sugars and generate energy through the pentose phosphate pathway. They are caused by defects in enzymes involved in this pathway.
Symptoms of inborn errors of carbohydrate metabolism can vary widely depending on the specific disorder and its severity. Treatment typically involves dietary restrictions, supplementation with necessary enzymes or cofactors, and management of complications. In some cases, enzyme replacement therapy or even organ transplantation may be considered.
The jejunum is the middle section of the small intestine, located between the duodenum and the ileum. It is responsible for the majority of nutrient absorption that occurs in the small intestine, particularly carbohydrates, proteins, and some fats. The jejunum is characterized by its smooth muscle structure, which allows it to contract and mix food with digestive enzymes and absorb nutrients through its extensive network of finger-like projections called villi.
The jejunum is also lined with microvilli, which further increase the surface area available for absorption. Additionally, the jejunum contains numerous lymphatic vessels called lacteals, which help to absorb fats and fat-soluble vitamins into the bloodstream. Overall, the jejunum plays a critical role in the digestion and absorption of nutrients from food.
Microvilli are small, finger-like projections that line the apical surface (the side facing the lumen) of many types of cells, including epithelial and absorptive cells. They serve to increase the surface area of the cell membrane, which in turn enhances the cell's ability to absorb nutrients, transport ions, and secrete molecules.
Microvilli are typically found in high density and are arranged in a brush-like border called the "brush border." They contain a core of actin filaments that provide structural support and allow for their movement and flexibility. The membrane surrounding microvilli contains various transporters, channels, and enzymes that facilitate specific functions related to absorption and secretion.
In summary, microvilli are specialized structures on the surface of cells that enhance their ability to interact with their environment by increasing the surface area for transport and secretory processes.
Pinnipedia is not a medical term, but a taxonomic category in zoology. It refers to a group of marine mammals that include seals, sea lions, walruses, and related extinct species. These animals are characterized by their limbs being modified into flippers, which makes them well-adapted for life in the water. They are often studied in fields such as marine biology and veterinary medicine.
I'm sorry for any confusion, but the term "shrews" is not a medical term. It is a common name used in zoology to refer to small mammals that are part of the family Soricidae and the suborder Soricomorpha. Shrews are insectivores, distantly related to moles and hedgehogs. If you have any questions about medical terminology or concepts, I would be happy to help!
Multienzyme complexes are specialized protein structures that consist of multiple enzymes closely associated or bound together, often with other cofactors and regulatory subunits. These complexes facilitate the sequential transfer of substrates along a series of enzymatic reactions, also known as a metabolic pathway. By keeping the enzymes in close proximity, multienzyme complexes enhance reaction efficiency, improve substrate specificity, and maintain proper stoichiometry between different enzymes involved in the pathway. Examples of multienzyme complexes include the pyruvate dehydrogenase complex, the citrate synthase complex, and the fatty acid synthetase complex.
Maltose is a disaccharide made up of two glucose molecules joined by an alpha-1,4 glycosidic bond. It is commonly found in malted barley and is created during the germination process when amylase breaks down starches into simpler sugars. Maltose is less sweet than sucrose (table sugar) and is broken down into glucose by the enzyme maltase during digestion.