scholarly journals A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine

2020 ◽  
Vol 77 (23) ◽  
pp. 4799-4826
Author(s):  
Hidde Elferink ◽  
Jeroen P. J. Bruekers ◽  
Gerrit H. Veeneman ◽  
Thomas J. Boltje

AbstractThe human body is able to process and transport a complex variety of carbohydrates, unlocking their nutritional value as energy source or as important building block. The endogenous glycosyl hydrolases (glycosidases) and glycosyl transporter proteins located in the enterocytes of the small intestine play a crucial role in this process and digest and/or transport nutritional sugars based on their structural features. It is for these reasons that glycosidases and glycosyl transporters are interesting therapeutic targets to combat sugar related diseases (such as diabetes) or to improve drug delivery. In this review we provide a detailed overview focused on the molecular structure of the substrates involved as a solid base to start from and to fuel research in the area of therapeutics and diagnostics.

F1000Research ◽  
2016 ◽  
Vol 3 ◽  
pp. 116 ◽  
Author(s):  
Giuseppe Musumeci ◽  
Ali Mobasheri ◽  
Francesca Maria Trovato ◽  
Marta Anna Szychlinska ◽  
Rosa Imbesi ◽  
...  

Osteoarthritis (OA) is a degenerative process involving the progressive loss of articular cartilage, synovial inflammation and structural changes in subchondral bone that lead to loss of synovial joint structural features and functionality of articular cartilage. OA represents one of the most common causes of physical disability in the world. Different OA treatments are usually considered in relation to the stage of the disease. In the early stages, it is possible to recommend physical activity programs that can maintain joint health and keep the patient mobile, as recommended by OA Research Society International (OARSI) and European League Against Rheumatism (EULAR). In the most severe and advanced cases of OA, surgical intervention is necessary. After, in early postoperative stages, it is essential to include a rehabilitation exercise program in order to restore the full function of the involved joint. Physical therapy is crucial for the success of any surgical procedure and can promote recovery of muscle strength, range of motion, coordinated walking, proprioception and mitigate joint pain. Furthermore, after discharge from the hospital, patients should continue the rehabilitation exercise program at home associated to an appropriate diet. In this review, we analyze manuscripts from the most recent literature and provide a balanced and comprehensive overview of the latest developments on the effect of physical exercise on postoperative rehabilitation in OA. The literature search was conducted using PubMed, Scopus, Web of Science and Google Scholar, using the keywords ‘osteoarthritis’, ‘rehabilitation’, ‘exercise’ and ‘nutrition’. The available data suggest that physical exercise is an effective, economical and accessible to everyone practice, and it is one of the most important components of postoperative rehabilitation for OA.


Light and electronmicroscopic observations of changes throughout the small intestine of foetal, and both suckled and unsuckled newborn pigs are reported. Foetal animals between 73 days gestation and term showed vacuolation in the terminal ileum. This was most extensive between 90 and 100 days when the terminal 30% of the small intestine contained vacuolated cells. The apical region of such cells contained a system of smooth tubes and vesicles, some of which showed evidence of a characteristic surface pattern. The vacuoles contained material of variable electron density and were sometimes seen apparently discharging their contents into the dilated intercellular spaces. Unsuckled newborn animals showed most of the features described above, but, in addition, the vacuolated cells contained large numbers of electron dense inclusions. In suckled animals from birth to 70 h of age there were considerable variations in cellular structure, which could be related to the position in the small intestine, the position on the villus and the age of the animal. The structural features described are discussed in relation to the transfer of colostrum immunoglobulins into the circulation. Keywords: swine, foetus, newborn, small intestine, structure.


2020 ◽  
Vol 295 (51) ◽  
pp. 17752-17769
Author(s):  
Evan M. Glasgow ◽  
Elias I. Kemna ◽  
Craig A. Bingman ◽  
Nicole Ing ◽  
Kai Deng ◽  
...  

Broad-specificity glycoside hydrolases (GHs) contribute to plant biomass hydrolysis by degrading a diverse range of polysaccharides, making them useful catalysts for renewable energy and biocommodity production. Discovery of new GHs with improved kinetic parameters or more tolerant substrate-binding sites could increase the efficiency of renewable bioenergy production even further. GH5 has over 50 subfamilies exhibiting selectivities for reaction with β-(1,4)–linked oligo- and polysaccharides. Among these, subfamily 4 (GH5_4) contains numerous broad-selectivity endoglucanases that hydrolyze cellulose, xyloglucan, and mixed-linkage glucans. We previously surveyed the whole subfamily and found over 100 new broad-specificity endoglucanases, although the structural origins of broad specificity remained unclear. A mechanistic understanding of GH5_4 substrate specificity would help inform the best protein design strategies and the most appropriate industrial application of broad-specificity endoglucanases. Here we report structures of 10 new GH5_4 enzymes from cellulolytic microbes and characterize their substrate selectivity using normalized reducing sugar assays and MS. We found that GH5_4 enzymes have the highest catalytic efficiency for hydrolysis of xyloglucan, glucomannan, and soluble β-glucans, with opportunistic secondary reactions on cellulose, mannan, and xylan. The positions of key aromatic residues determine the overall reaction rate and breadth of substrate tolerance, and they contribute to differences in oligosaccharide cleavage patterns. Our new composite model identifies several critical structural features that confer broad specificity and may be readily engineered into existing industrial enzymes. We demonstrate that GH5_4 endoglucanases can have broad specificity without sacrificing high activity, making them a valuable addition to the biomass deconstruction toolset.


1990 ◽  
Vol 68 (11) ◽  
pp. 1482-1488 ◽  
Author(s):  
Balwant S. Tuana ◽  
Brian J. Murphy

The development of specific pharmacological agents that modulate different types of ion channels has prompted an extensive effort to elucidate the molecular structure of these important molecules. The calcium channel blockers that specifically modulate the L-type calcium channel activity have aided in the purification and reconstitution of this channel from skeletal muscle transverse tubules. The L-type calcium channel from skeletal muscle is composed of five subunits designated α1, α2, β, γ, and σ. The α1-subunit is the pore-forming polypeptide and contains the ligand binding and phosphorylation sites through which channel activity can be modulated. The role of the other subunits in channel function remains to be studied. The calcium channel components have also been partially purified from cardiac muscle. The channel consists of at least three subunits that have properties related to the subunits of the calcium channel from skeletal muscle. A core polypeptide that can form a channel and contains ligand binding and phosphorylation sites has been identified in cardiac preparations. Here we summarize recent biochemical and molecular studies describing the structural features of these important ion channels.Key words: dihydropyridine receptor, calcium channel, muscle, molecular structure.


1967 ◽  
Vol 21 (2) ◽  
pp. 399-411 ◽  
Author(s):  
M. C. Nesheim ◽  
K. J. Carpenter

1. The apparent digestibilities for chicks, operated on so as to allow separate collection of urine and faeces, of the nitrogen in a heat-damaged cod flour (C35) and of a control, freezedried cod muscle (C23) were 77 and 90% respectively.2. The differences are similar to those found for rats in earlier work and considerably smaller than the differences found in nutritional value of the materials as sources of either lysine or methionine for chicks.3. Chicks killed 3 h after a test meal containing C23 showed little more N in their small intestine than did those on a N-free diet; other chicks receiving C35 showed much more N remaining in the gut.4. It is hypothesized that significant quantities of heat-damaged protein may remain undigested in the small intestine, but may then be de-aminated by fermentation in the caecum so that values for the digestibility of N and of individual amino acids may be misleadingly high.5. This hypothesis is supported by the finding that in caecectomized chicks the apparent digestibility of the N of C35 was only 68%, whereas the digestibility of C23 remained the same as in intact chicks.


2012 ◽  
Vol 90 (8) ◽  
pp. 640-651
Author(s):  
Jing Song ◽  
Ying Zhang ◽  
Hui Hu ◽  
Hui Zhang ◽  
Lin Lin ◽  
...  

Quantitative structure–property relationship (QSPR) studies were performed for the prediction of gas-phase reduced ion mobility constants (K0) of diverse compounds based on three-dimensional (3D) molecular structure representation. The entire set of 159 compounds was divided into a training set of 120 compounds and a test set of 39 compounds according to Kennard and Stones algorithm. Multiple linear regression (MLR) analysis was employed to select the best subset of descriptors and to build linear models, whereas nonlinear models were developed by means of an artificial neural network (ANN). The obtained models with five descriptors involved show good predictive power for the test set: a squared correlation coefficient (R2) of 0.9029 and a standard error of estimation (s) of 0.0549 were achieved by the MLR model, whereas by the ANN model, R2 and s were 0.9292 and 0.496, respectively. The results of this study compare favorably to previously reported prediction methods for the ion mobility constants. In addition, the descriptors used in the models are discussed with respect to the structural features governing the mobility of the compounds.


1975 ◽  
Vol 48 (4) ◽  
pp. 705-718 ◽  
Author(s):  
C. J. Carman ◽  
K. C. Baranwal

Abstract Characterization and identification of elastomers are important analytical needs for those involved in rubber technology. High resolution pulsed Fourier transform 13C NMR has been shown to be a powerful tool which can supply much detail as to sequence distribution, chain configuration, steric purity, or identification of polymer mixtures. One can also use 13C to distinguish polymer blends from copolymers of similar composition. This information about elastomers commonly used in the rubber industry provides not only a new tool for analytical problem solving, but also provides analytical information to guide the chemist as he makes elastomeric materials with structural features which impart specific physical properties.


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