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Fucosidosis
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Fucose is a deoxysugar, an aldohexose in which the terminal CH2OH is replaced by a methyl group (Figure 95.1). It occurs in glycoproteins and glycolipids as a terminal oligosaccharide linked to galactose or N-acetylglucosamine (Figure 95.2). The degradation of glycoproteins takes place sequentially in the lysosomes. Fucosidosis is a glycoprotein storage disease in which patients have impaired degradation of fucose-containing glycoproteins.
Effect of Solute Structure on Transport of Radiotracers
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
The use of various sidechains containing hydroxyl, sulfhydryl, and amino groups on the sidechain of amino acids as sensors for the position of sodium has led to the study of sodium as a possible co-substrate also for the transport of sugar. The sodium-dependent transport of glucose appears to be dependent on the 2-hydroxyl group as shown by the work of Kleinzeller who demonstrated an exclusive sodium-independent transport for 2-deoxy sugars.8
Peripheral Mechanisms of Mammalian Sweet Taste
Published in Robert H. Cagan, Neural Mechanisms in Taste, 2020
William Jakinovich, Dorothy Sugarman
Ideally, the structure-activity requirements of sugar taste responses can be studied using methyl glycosides, 1,5 anhydrotols (1-deoxy-sugars), and cyclitols. Unlike the reducing sugars, these compounds do not mutarotate to form a mixture of isomers, but adopt well-defined conformations and configurations.64 Because cyclitol and anhydrotol derivatives are not readily available, the methyl d-glycosides have been used most frequently in monosaccharide structure-activity studies involving gustation. Those methyl glycopyranosides that differ in the orientation of their C-l substituents are known as anomers: the axially oriented substituent is known as a and the equatorially oriented substituent is known as β. Those methyl d-glycopyranosides that differ in orientation at C-2, C-3, C-4, or C-5 are known as epimers.
Antioxidant activity of curcumin protects against the radiation-induced micronuclei formation in cultured human peripheral blood lymphocytes exposed to various doses of γ-Radiation
Published in International Journal of Radiation Biology, 2021
The ionizing radiations (IR) are known to deposit energy randomly in mammalian cells. This triggers numerous molecular damages leading to a variety of cellular responses, including mutations, chromosomal rearrangements, and finally cell inactivation (Wallace 1994). IR-induced molecular damage is mediated by triggering indirectly hydroxyl free radicals (•OH) or by direct ionization. The •OH radicals interact with cellular DNA and alter deoxy sugar and DNA bases, which are consequently transformed into DNA single-strand breaks (SSBs), or double-strand breaks (DSBs) later (Wallace 1994; Landuzzi et al. 2017). The deleterious molecular alterations elicited in the cell genome by IR give rise to cancer and other hereditary diseases. The high energy deposited by IR has the potential to produce DNA DSBs, which makes IR effective in inducing chromosomal aberrations and genomic instability (Shimura and Kojima 2018). The cytogenetic biomarkers like sister chromatid exchanges, chromosomal aberrations, and micronuclei in HPBLs have been used to detect low-dose exposures to mutagens or carcinogens and work environment surveillance (Anderson 2019). The micronucleus assay is simple and can be done with ease and scoring of micronuclei serves as an index of genomic instability induced by chemical and/or physical agents (Sommer et al. 2020). Therefore, scoring of micronuclei could be a useful paradigm in the evaluation of the radioprotective activity of pharmacological agents in vitro and in vivo (Jagetia 2007a).
Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health
Published in Gut Microbes, 2020
Arghya Mukherjee, Cathy Lordan, R. Paul Ross, Paul D. Cotter
Propionate can be formed via two pathways from sugar fermentation by gut microbes. While the succinate pathway processes most pentose and hexose sugars to produce propionate, deoxy sugars such as fucose and rhamnose are metabolized by the propanediol pathway. The latter are readily available in the gut environment as dietary (e.g. human milk oligosaccharides) or host-derived (mucin) glycans and upon utilization by a variety of gut microbes can produce 1,2-propanediol as an end product. Although unable to degrade deoxy sugars, 1,2-propanediol can be metabolized by E. hallii, which has been shown to carry the glycerol/diol dehydratase PduCDE, a key enzyme in the transformation of 1,2-propanediol to produce propionate and propanol with the generation of one ATP.64,65 The conversion of 1,2-propanediol to propionate is dependent on the availability of vitamin B12 and occurs within microcompartments called polyhedral bodies to sequester the toxic intermediate, propionaldehyde.66
Macrolides for KCNJ5–mutated aldosterone-producing adenoma (MAPA): design of a study for personalized diagnosis of primary aldosteronism
Published in Blood Pressure, 2018
Giuseppe Maiolino, Giulio Ceolotto, Michele Battistel, Giulio Barbiero, Maurizio Cesari, Laurence Amar, Brasilina Caroccia, Roberto Padrini, Michel Azizi, Gian Paolo Rossi
The recent discovery that G151R and L168R, the most common KCNJ5 mutations render the Kir3.4 channel exquisitely sensitive to inhibition by some macrolide antibiotics and some of their non-antibiotic derivatives. These agents blunted concentration-dependently aldosterone production in vitro in HAC-15 cells transfected with heterodimers carrying these two mutations provided ground-breaking evidence that the altered physiology of this channelopathy could be corrected by a specific pharmacologic intervention with commonly used macrolides [11]. These antibiotics feature a many-membered lactone ring with one or more deoxy sugars attached [19] and exerts their antibacterial activity by inhibiting protein synthesis by binding of the desosamine sugar and the lactone ring to bacterial 23S ribosomal RNA [20]. Binding to other targets produces anti-inflammatory activity [21], which can have clinical utility, and stimulation of gastrointestinal motility that can cause side effects [22]. A systematic analysis of 14 different macrolides showed that clarithromycin and roxithromycin were among the most potent macrolide antibiotics to inhibit the Kir3.4 channel with G151R and L168R mutations [11].