Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanosomes and lysosomes share several structural and biosynthetic properties. Therefore, a large number of mouse pigment mutants were tested to determine whether genes affecting melanosome structure of function might also affect the lysosome. Among 31 mouse pigment mutants, six had 1.5- to 2.5-fold increased concentrations of kidney beta-glucuronidase. Three mutants, pale ear, pearl and pallid, had a generalized effect on lysosomal enzymes since there were coordinate increases in kidney beta-galactosidase and alpha-mannosidase. The effects of these three mutations are lysosome specific since rates of kidney protein synthesis and activities of three nonlysosomal kidney enzymes were normal. Also, the mutants are relatively tissue specific in that all had normal liver lysosomal enzyme concentrations.--A common dysfunction in all three mutants was a lowered rate of lysosomal enzyme secretion from kidney into urine. While normal C57BL/6J mice daily secreted 27 to 30% of total kidney beta-glucuronidase and beta-galactosidase, secretion of these two enzymes was coordinately depressed to 1 to 2%, 8 to 9% and 4 to 5% of total kidney enzyme in the pale-ear, pearl and pallid mutants, respectively. Although depressed lysosomal enzyme secretion is the major pigment mutant alteration, the higher lysomal enzyme concentrations in pearl and pallid may be partly due to an increase in lysosomal enzyme synthesis. In these mutants kidney glucuronidase synthetic rate was increased 1.4- to 1.5-fold.--These results suggest that there are several critical genes in mammals that control the biogenesis, processing and/or function of related classes of subcellular organelles. The mechanism of action of these genes is amenable to further analysis since they have been incorporated into congenic inbred strains of mice.
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PMID:Lysosomal dysfunctions associated with mutations at mouse pigment genes. 11 47

The kidney and urine glycosphingolipids of five pigmentation mutants which are known to have altered secretion of kidney lysosomal enzymes were examined. Among 34 pigmentation mutants which have been studied (Novak, E. K., Wieland, F., Jahreis, G. P., and Swank, R. T. (1980) Biochem. Genet. 18, 549-561) eight are known to have a 1.5- to 2.5-fold increase in kidney beta-glucuronidase in testosterone-treated females. These mutants appear to have defects in lysosomal processing, and because the mutations are at separate loci, each mutant probably affects different steps in assembly and/or exocytosis of lysosomes and related subcellular organelles. To test whether the neutral glycosphingolipids, galabiglycosylceramides, and globotriglycosylceramides thought to be associated with kidney lysosomes (McCluer, R. H., Williams, M. A., Gross, S. K., and Meisler, M. H. (1981) J. Biol. Chem. 256, 13112-13120) also exhibit abnormal secretion in the mutants with lysosomal enzyme abnormalities, the mutants beige-J, pale ear, light ear, pallid, and ruby eye-2-J were studied. The kidney and urine neutral glycosphingolipids from males of each mutant and C57BL/6J control mice were analyzed by high performance liquid chromatography. Beige-J, light ear, and pale ear showed marked increases in total kidney glycolipids; globotriglycosylceramides accounted for the bulk of the increase. Ruby eye-2-J showed less marked but significantly increased quantities of one galabiglycosylceramide and the globotriglycosylceramides in kidney. Pallid showed no significant increase in total kidney glycolipids but the globotriglycosylceramides appeared slightly elevated. In terms of the decrease in total urinary glycosphingolipids, the mutants fell into 2 categories. Beige-J, light ear, and pale ear were severely affected, whereas ruby eye-2-J and pallid were affected to a much lesser extent. Within the most severely affected group the excretion of the globotriglycosylceramides was more severely affected than that of the galabiglycosylceramides. The galabiglycosylceramides and globotriglycosylceramides appear to be specific markers of lysosomal membranes, but the independent behavior of these two classes of lipids during testosterone induction in normal mice and the differential effects on their secretion by different mutants indicate that they do not always exist in a characteristic ratio in a single type of subcellular organelle. All of the mutants accumulate organelles in their kidney proximal tubules which have distinct morphological characteristics as seen by electron microscopy.
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PMID:Altered secretion and accumulation of kidney glycosphingolipids by mouse pigmentation mutants with lysosomal dysfunctions. 398 43