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Constitutive Host Resistance
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Cells of the mononuclear phagocyte lineage initially contain granules; these are lost during differentiation. The mononuclear phagocytes, which comprise from two to eight percent of the circulating leukocytes, contain enzymes similar to those present in neutrophils (Table 3.1). The enzymes are contained within bags bounded by membranes, called lysosomes. The mononuclear phagocyte is long-lived and continues to synthesize enzymes throughout its life. The acid hydrolases of mononuclear phagocytes act at acidic pH and cleave phosphate ester bonds that occur in proteins, polysaccharides, lipids, and nucleic acids. The enzymes are distinguished by their substrates and include fucosidase, 5′nucleotidase, galactosidase, arylsulfatase, mannosidase, N-acetyl-glucosaminidase, glucuronidase, and glycerophosphatase. Other enzymes included in this group are responsible for protein hydrolysis and are called cathepsins A, B, and C, and so on. Neutral proteases include cathepsin G, whose substrates are cartilage, proteoglycans, fibro-gen, and casein, and the enzymes, eiastase and collagenase. The latter two enzymes have been shown to play an important role in the destruction of normal tissues that may occur during an inflammatory response. The peroxidase enzyme catalase protects the phagocytes from the toxic effects of the hydrogen peroxide produced following the binding and phagocytosis of foreign substances.
Fucosidosis
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Defective activity of the enzyme can be demonstrated in leukocytes and cultured fibroblasts [14, 38, 39]. Routine assays use artificial substrates and fluorimetric or colorimetric analysis. The different phenotypes cannot be distinguished by enzymatic assay as activity is essentially absent in all. There is fucosidase activity in serum or plasma, but assay is not a reliable method of diagnosis, as some normal individuals have low levels of activity in the fluid [40]. Heterogeneity among patients has been shown by the assessment of amounts of enzyme protein [41]; of 11 patients with markedly defective enzyme activity, eight made no enzyme protein in fibroblasts; in two, the amounts of the 53 kDa precursor were normal, but there were no mature 50 kDa form; in one, there was a small amount of CRM.
Lysosomal, sterol and lipid disorders
Published in Steve Hannigan, Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
Fucosidosis is a rare inherited disorder that belongs to a group of conditions known as lysosomal storage disorders. It is caused by an absence or a deiciency of the enzyme alpha-L-fucosidase, which results in impaired fucosidase activity. Partially degraded chemicals that contain fucose remain in the body, accumulate and cause progressive damage to the cells. The defective gene (FUCA2) is located on the short arm of chromosome 1. Researchers believe that there are two types of this disorder, determined mainly by the severity of the symptoms.
Identification of Allobaculum mucolyticum as a novel human intestinal mucin degrader
Published in Gut Microbes, 2021
Guus H. van Muijlwijk, Guido van Mierlo, Pascal W.T.C. Jansen, Michiel Vermeulen, Nancy M.C. Bleumink-Pluym, Noah W. Palm, Jos P.M. van Putten, Marcel R. de Zoete
Mucin O-glycans, such as the typical core 2 mucin O-glycan depicted in figure 5f, are made up of multiple covalently linked monosaccharides. To degrade such glycans the linkages between the different monosaccharides need to be hydrolyzed by CAZymes with the correct linkage specificity. To verify whether the CAZymes secreted by A. mucolyticum are enzymatically active and able to hydrolyze linkages found in mucin O-glycans, conditioned medium or heat-inactivated conditioned medium (30 minutes at 98°C) from a 48 h culture was incubated with five different monovalent fluorescent or chromogenic substrates to detect the presence of sialidase, fucosidase, galactosidase, N-acetyl-glucosaminidase and N-acetyl-galactosaminidase activities. This resulted in clear signals for the presence of α-sialidase, β-galactosidase, β-GlcNAcase and α-GalNAcase activities in A. mucolyticum conditioned medium (Figure 4a-e). Although multiple fucosidases were detected in the secretome during the proteomics analysis, no fucosidase activity could be detected – even after concentrating the culture media 100x. An alternative approach using chemoselective labeling of the fucosidases with an activity-based probe, which can detect fucosidase activity in enzymes with both GH29 and GH95 glycosyl hydrolase domains, also did not detect fucosidase activity. Despite the lack of fucosidase activity, the combination of identified enzymatic activities would likely be able to effectively target and degrade O-linked glycans, such as found on mucins.
Proteomics-inspired precision medicine for treating and understanding multiple myeloma
Published in Expert Review of Precision Medicine and Drug Development, 2020
Matthew Ho, Giada Bianchi, Kenneth C. Anderson
Cell membrane protein glycosylation has also been studied in MM. MM cells express high levels of P-selectin glycoprotein ligand 1 which mediate binding to E- and P-selectins [108]. This facilitates MM homing and adhesion to the cells in the BM microenvironment. Overexpression of ST3GAL6, a sialyltransferase that plays a key role in the synthesis of sialyl-Lewisx, predicts poor OS in MM [109]. Mechanistic studies reveal that knockdown of ST3GAL6 led to a reduction in α2-3-linked sialic acid on the MM cell surface membrane, which resulted in decreased stromal adhesion in vitro and reduced homing and engraftment in vivo [109]. Reduced FUCA1; an alpha-L-fucosidase that catalyzes the hydrolysis of α1-3, α1-4, and α1-6 linked fucose; was also associated with poor OS in MM [110].
Long-term changes of salivary exoglycosidases and their applicability as chronic alcohol-drinking and dependence markers
Published in The World Journal of Biological Psychiatry, 2019
Napoleon Waszkiewicz, Ewa Maria Kratz, Sylwia Chojnowska, Anna Zalewska, Krzysztof Zwierz, Agata Szulc, Sławomir Dariusz Szajda, Anastasiya Nestsiarovich, Andrei Kapitau, Alina Kępka, Lucyna Ostrowska, Mirosława Ferens-Sieczkowska
Alpha-fucosidase, GAL, GLU, HEX, HEX A and HEX B isoenzymes, and MAN are lysosomal exoglycosidases involved in the degradation of the oligosaccharide chains of glycoconjugates through the release of monosaccharides from their oligosaccharide chains (Waszkiewicz et al. 2011a, 2012a). It was suggested that some glycochanges, such as fucosylation, have a tendency to correct after an abstinence period of 7 weeks in alcohol-dependent patients (Kratz et al. 2014). It was also found that smoking alcohol-dependent persons have more profound and longer decrease (until the 30th day of alcohol abstinence) in some alcohol-metabolising enzymes (e.g. alcohol dehydrogenase (ADH)) in the saliva than non-smoking individuals (Waszkiewicz et al. 2014a). Therefore the aim of this study is: (a) to investigate whether changes in the activity of exoglycosidases (Waszkiewicz et al. 2014b) are still present after ∼7weeks (at the 50th day) of the abstinence period in smoking and non-smoking alcohol-dependent persons; (b) to find if some of these alcohol markers (especially HEX A and GLU) have worse, the same, or better 50th-day accuracy as markers of alcohol dependence than at first day of the abstinence; (c) to check if deglycosylation processes are still active in the saliva at the 50th day of abstinence.