Galactosialidosis
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Once the primary structure of the protein was known, its homology to yeast and plant serine carboxypeptidases became apparent [66]. The protective protein was then shown to have carboxypeptidase activity [67], and this activity is deficient in galactosialidosis. The properties of this carboxypeptidase are consistent with those of cathepsin A [59]. Site-directed mutagenesis which abolishes cathepsin activity does not interfere with protective activity; so, the two functions are distinct [59]. Nevertheless, cathepsin A activity provides a simple test that is useful for heterozygote detection. The fact that the protective function and cathepsin activity are distinct provides an argument for continued diagnostic reliance on the assay of β-galactosidase and neuraminidase in leukocytes or fibroblasts [58, 59]. The three enzyme activities, cathepsin, β-galactosidase, and neuraminidase, copurify [58]. PPCA and galactosidase are found separate from the complex, but all of the neuraminidase is present in the complex [68]. PPCA functions as an intracellular transport protein [69]. It has a mannose-6-phosphate recognition marker [70]. The enzyme also has deamidase and esterase activities, and these activities are deficient in cultured cells of patients [71].
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow in Fetal and Perinatal Skeletal Dysplasias, 2012
Dysostosis multiplex – lysosomal storage disorders: MPS I->H – also known as Hurler disease, more common than ML2, presents with more marked clinical signs of ‘storage’ and less severe dysostosis multiplex on radiographs; due to deficiency of the enzyme alpha-L-iduronidase (IDUA). GM1-gangliosidosis type 1: similar features, usually lethal in the first years of life, extensive skin mongolian blue spots and retinal cherry red spots; caused by deficiency of beta-galactosidase-1 (GLB1). Infantile galactosialidosis: the early onset form may show fetal hydrops, ascites, visceromegaly, macular cherry red spot, early death; caused by recessive mutations in the gene CTSA (cathepsin A). Infantile sialic acid storage disease (ISSD): severe organ involvement (hepatosplenomegaly, cardiomegaly, nephrotic syndrome), hydrops, ascites, early death. Caused by recessive mutations in the gene SLC17A5.
Interaction of Amebas with Cells
Roberto R. Kretschmer in Amebiasis: Infection and Disease by Entamoeba histolytica, 2020
Lushbaugh and co-workers62 associated the cytotoxic activity with a neutral thiol proteinase with molecular weight about 24 kDa, active on azocasein at pH 6. Such an activity had been previously described63 and was shown to be greater in the more virulent strains. The thiol proteinase described had a molecular weight of 16 kDa and was inhibited by leupeptin and serum and activated by free sulphydril groups so that it resembled cathepsin B. 61,64 A weakly acid or neutral thiol proteinase has been described by a number of groups.65-70 The reports vary as to the exact molecular weight of the protein but it seems likely that the denatured enzyme has a molecular weight of between 16 to 30 kDa and that higher molecular weight species represent artifacts of the gel procedures due to partially native forms.61,70 From the substrate preferences and N-terminal sequence61,67,70 the enzyme resembles but is not identical to cathepsin B.
Cardio-protective effects of terminalia catappa leaves and terminalia chebula fruit extract in doxorubicin-induced cardiomyopathy in rats
Published in Biomarkers, 2022
Ramasamy Manikandan, Balamuralikrishnan Balasubramanian, Panneerselvam Punniyakotti, Arumugam Vijaya Anand, Arun Meyyazhagan, Shanmugam Velayuthaprabhu, Rengasamy Lakshminarayanan Rengarajan, Utthapon Issara, Wen-Chao Liu
In the present study, the Tct.LE and Tce.FE, propranolol enhances the activities of TCA cycle enzymes, these may improve the mitochondrial antioxidant defence system and overcome the complications with the decreased TCA cycle function. The treatment with Tct.LE and Tce.FE, propranolol may reduce the oxidative damage in the mitochondria and enhances the antioxidant status. The decrease in mitochondrial antioxidants could be due to the feedback inhibition or oxidative inactivation of enzyme protein caused by the excess ROS generation (Al-Assaf 2014). Cathepsin D is a lysosomal enzyme, which is present in all animal cells (Sudharsan 2006). It is mainly involved in the autophagic digestion of discrete parts of the cytoplasm and the proteins present in the myofibrillary and mitochondria. This type of lysosomal enzymes stimulates the oxygen radical; it disturbs the cardiac tissues. These are in agreement with Suchalatha and Devi (2005), who reported that the levels of β-D-glucuronidase and β-N-acetyl glucosaminidase levels are reduced in the T. chebula treats in the isoproterenol-induced cardiac damage in rats.
Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration
Published in Organogenesis, 2019
Yoshihiro Matsumoto, Tomoharu Yoshizumi, Takeo Toshima, Kazuki Takeishi, Takasuke Fukuhara, Shinji Itoh, Toru Ikegami, Yuji Soejima, Masaki Mori
Next, we examined the involvement of pathways in steatotic liver regeneration. In m+/m+ mice, the peak LC3-II level was observed at 12 h after 70% PH, while the p62 protein, which regulates ubiquitinated protein, was increased gradually at least 48 h. However, in db/db mice, the LC3-II level was higher and p62 expression was notably increased in db/db mice compared with m+/m+ mice (Fig. 3), while Atg5-12 expression levels were nearly equal in both groups. These results suggest that autophagosome formation is not suppressed, but autophagic proteolysis is inhibited in db/db mice compared with controls. Thus, the cathepsin D protein level, a proteinase of lysosomes, was evaluated. As expected, cathepsin D expression was suppressed in db/db mice compared with controls (Fig. 3).
Distinctive alteration in the expression of autophagy genes in Drosophila models of amyloidopathy and tauopathy
Published in Upsala Journal of Medical Sciences, 2020
Mehrnaz Haghi, Raheleh Masoudi, Seyed Morteza Najibi
Association of autophagosome with lysosome is the last step of autophagy. Finally, its internal components are degraded by lysosome hydrolases like Cathepsin D (17). Cathepsin D is the only proteolytic enzyme the expression of which, in different tissues, is regulated in response to growth factors, cytokines, and vitamins (58). Cathepsin D-mediated proteolysis is essential to neurons because it degrades unfolded/oxidized protein aggregates that continuously reach the lysosomes via autophagy or endocytosis (43). Many proteins produced in neurons are physiologic substrates of Cathepsin D and will be abnormally accumulated if they are not efficiently degraded (e.g. APP, α-synuclein, and huntingtin). Therefore, dysfunction of Cathepsin D in the lysosomal system is closely related to the mechanism underpinning neurodegeneration (43).
Related Knowledge Centers
- Carboxypeptidase
- Cathepsin
- Enzyme
- Neuraminidase
- Gene
- Β-Galactosidase
- Galactosialidosis
- Protein–Protein Interaction
- Sialidase-1