Neuraminidases lysosomal

There are other lysosomal disorders in addition to those shown in Figure 9.20 and Table 9.1. For instance, several types of fucosidoses exist, which affect such structures as glycoproteins and blood group substances. Sialidoses also exist. However, lysosomal fucosidase and sialidase (neuraminidase) deficiencies do not affect the degradation of gangliosides. 

Zanamivir has poor oral systemic availability. Intranasal administration slightly increases its availability, but in mice strongly reduced viral replication (4). In vitro, zanamivir does not significantly inhibit human lysosomal neuraminidases, and so the potential for severe adverse effects is low (5). 

E. Bonten, A. van der Spoel, M. Fomerod, G. Grosveld, and A. d Azzo, Char-aeterization of human lysosomal neuraminidase defines the molecular basis of flic metaboUc storage disorder siaUdosis, Genes Dev, 10 (1996) 3156-3169. 

E. J. Bonten and A. d Azzo, Lysosomal neuraminidase. Catalytic activation in insect cells is eontrolled by the protective protein/cathepsin A, J. Biol. Chem., 275 (2000) 37657-37663. 

A. Hinek, A. V. Pshezhetsky, M. von Itzstein, and B. Starcher, Lysosomal siahdase (neuraminidase-1) is targeted to die cell surface in a multiprotein complex diat facilitates elastic fiber assembly, J. Biol Chem., 281 (2006) s3698-3710. 

X. Wu, K. A. Steigelman, E. Bonten, H. Hu, W. He, T. Ren, J. Zuo, and A. d Azzo, Vacuolization and alterations of lysosomal membrane proteins in cochlear marginal cells contribute to hearing loss in neuraminidase 1-deficient mice, Biochim. Biophys. Acta, 1802 (2010) 259-268. 

It should be remembered, that a defect of lysosomal neuraminidase is likely to be the immediate cause of I-cell disease, but the fundamental error is in the phosphorylation of several hydrolases, of which the neuraminidase will simply be the first to act in normal degradation. 

Neuraminidase Deficiency. A simple defect in lysosomal neuraminidase has only recently come to light (Lowden and O Brien, 1979 Kuriyama etal, 1979). Patients with this storage disease put out sialo-oligosaccharides in their urine. Fibroblasts from the patient of Kuriyama et al, (1979) showed an extreme deficiency in neuraminidase activity towards a2,3-sialyl lactose, a2,6-sialyl lactose and fetuin. Hence more than one enzyme might be involved. 

Glycoprotein sialidase (neuraminidase) (EC 3.2.1.18). Other lysosomal activities in liver sometimes increased. Sialyloligosaccharides accumulate. Mental retardation, skeletal abnormalities and Hurler-type facial features may be present in varying degrees, or absent. Hepatosplenomegaly, renal involvement and hydrops fetalis sometimes present. 

Fibroblasts from a patient with mucolipidosis I showed a five-fold increase in the level of sialic acid and a lower-than-normal level of lysosomal neuraminidase, which results in impaired catabolism of glycopeptides and glycolipids containing sialic acid. A D-mannosyltransferase has been found in suspensions of Balb/c fibroblasts incubated with GDP-D-[ C]mannose it appears to be present at the cell surface, where it is involved in the synthesis of glycolipids and glycoproteins. ... 

The extractability, solubility, and intraneuronal distribution of brain cytosol neuraminidase of pigs have been studied. The enzyme from nerveending cytosol, and neuronal body and glial cell cytosol appeared to differ somewhat in their physicochemical and kinetic properties. Comparisons were made of the behaviour of the neuraminidases with that of lysosomal jS-D-galactosidase and /S-D-2-acetamido-2-deoxyhexosidase. 

In normal and regenerating rat liver tissue, neuraminidase has been shown to be localized primarily in the fraction of light mitochondria, enriched with lysosomes. Actinomycin D and cycloheximide did not lower the neuraminidase activity of lysosomes of the regenerating liver, indicating absence of de novo biosynthesis of the enzyme in the process of tissue regeneration. 

Hiraiwa summarized in his review the basic understanding of CatA biology [7]. A prominent role of CatA is the protection of lysosomal 15-galactosi-dase (P-gal) and neuraminidase 1 (Neu-1) from intralysosomal proteolysis by the formation of a multienzyme complex [8,9]. This complex is responsible for the breakdown of oligosaccharides attached to a variety of glycoproteins and glycolipids. 

Pshezhetsky, A.V. and Potter, M. (1996) Association of JV-acetyl-galactosainine-6-suliate suliatase with the multienzyme lysosomal complex of B-galactosidase, cathepsin A and neuraminidase possible implication for intralysosomal catabolism of keratan sulfate. Journal ofBiolo cal Chemistry, 271,28359 28365. 

In addition to these two types of sialidosis, there are patients with a combined defect of neuraminidase and p-galactosidase (Wenger etal. 1978, Andria etal. 1978, OK.ADAetal. 1979), possibly caused by a common defect in the biosynthetic processing of the two enzymes (Hoogeveen etal. 1980). A neuraminidase deficiency has also been observed in patients with mucolipidosis II (I-cell disease) and mucolipidosis III (Strecker etal. 1976, Thomas etal. 1976). In these disorders, however, the neuraminidase deficiency is but one of many lysosomal hydrolase deficiencies, presumably due to a defect in the proper compart-mentalization of these enzymes (Neufeld 1974). 

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