Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta-N-acetylhexosaminidase exhibits a relatively high activity in human epididymis. Its isoenzymatic profile and immunological properties led us to conclude that the increased activity was not due to the expression of an isoform unrelated to the HEX A and B present in other human tissues. Measurement of enzyme levels in the three distinct epididymal regions revealed that in any given sample, activity was higher in the caput than in the corpus or cauda. Moreover, we found a striking correlation between beta-HEX activity in the caput region and concentrations of blood testosterone, suggesting a possible involvement of the hormone in modulating enzyme expression. Since the caput epididymis plays a role in the maturation of sperm cells, our data may be an indication that beta-HEX activity in the caput has a physiological relevance in human epididymis functions.
Biochem Mol Biol Int 1993 Aug
PMID:Blood testosterone levels are correlated with beta-N-acetylhexosaminidase activity in human caput epididymis. 822 Feb 48

The N-linked oligosaccharide moieties of sycamore (Acer pseudoplatanus L.) laccase are known to be highly heterogeneous. We confirmed that this oligosaccharide heterogeneity was caused not only during the oligosaccharide biosynthesis in Golgi apparatus, but also after the excretion of laccase protein into a culture medium. The culture medium for the sycamore cells (Acer pseudoplatanus L.) contained beta-galactosidase, alpha-L-fucosidase, beta-N-acetylglucosaminidase, alpha-mannosidase and beta-xylosidase activities. We showed that the largest sugar chain in laccase, oligosaccharide F, [formula: see text] was degraded to [formula: see text] by a crude exoglycosidase mixture in the culture medium.
Biochem Mol Biol Int 1993 Mar
PMID:Occurrence of heterogeneity of N-linked oligosaccharides attached to sycamore (Acer pseudoplatanus L.) laccase after excretion. 848 57

The heterogeneity of mutations causing Tay-Sachs disease in non-Jewish populations requires efficient techniques allowing the simultaneous screening for both known and novel mutations. beta-hexosaminidase mRNA isolated from cultured fibroblasts of 19 Tay-Sachs patients (7 with adult or late onset form of the disease and 12 with infantile Tay-Sachs disease) was amplified by cDNA-PCR in two overlapping segments spanning the entire coding sequence. We used chemical mismatch cleavage (CMC), denaturing gradient gel electrophoresis (DGGE) and direct sequencing of amplified fragments displaying a cleaved product or an altered melting behavior to screen the HEX A gene for mutations and to determine their distribution and frequency in the non-Jewish Tay-Sachs patients. These methods allowed us to identify 31 out of 38 alleles studied (82%). In addition to 9 previously described mutations (the 4 bp insertion in exon 11, G to A transitions at codons 170, 269, 482, 499 and 504, C to T transition at codon 499 and 504 and a GT to AT transition at the donor site of intron 9), we have identified 10 novel mutations. These include 1 donor splice site defect in intron 6, 8 missense mutations at non-randomly distributed conserved residues and a 2 bp deletion in exon 4. These results confirm the extreme molecular heterogeneity of mutations causing Tay-Sachs disease in non-Jewish population. The strategy used should be profitable for identifying mutations in large genes and for diagnostic purposes.
Hum Mol Genet 1993 Jan
PMID:Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients. 849 Jun 25

The biochemical properties of hexosaminidase A (HexA) and the coding sequence of the alpha-subunit were examined in a patient of Syrian ancestry with the B1 form of Tay-Sachs disease (TSD). The biochemical characteristics of the variant HexA suggest that both active sites are affected by the mutation(s). Kinetic studies with the beta-subunit specific substrate, 4-methylumbelliferyl-beta-D-N-acetylglucosamine (MUG), revealed a significant difference between the Km values. of normal and variant HexA, while no difference was found when the sulfated substrate MUG-6-sulfate (MUGS), which is specific for the alpha-subunit active site, was used. The Vmax values for both substrates were significantly lower in extracts from B1 variant cells than in control extracts, implying a reduced enzyme level in the variant cells. A noncompetitive inhibitor of the reaction with MUGS, N-acetylglucosamine (NAG), induced a significant inhibition (30%) in the mutant cells only. When MUG was used as substrate, variant HexA was found to be more heat stable (T50 = 170 min) than normal HexA (T50 = 65 min). Furthermore, the mutant cell preparation differed from control in the relation between Hex thermosensitivity and protein concentration in the reaction. Two new mutations were identified in exon 5 of the HexA gene: a C496 to G transversion, which produced an Arg166 -->Gly alteration and a deletion of C498 which generated a shift in the reading frame. The patient was a heterozygote for both mutations even though her parents are first cousins. There is no evidence as yet which of these mutations accounts for the B1 phenotype.
Biochem Mol Med 1995 Apr
PMID:GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A. 858 57

Chitinolytic enzymes such as beta-N-acetylglucosaminidases are major hydrolases involved in insect molting. By screening a Manduca sexta (tobacco hornworm) cDNA library with an antibody against beta-N-acetylglucosaminidase from molting fluid of M. sexta pharate pupae, several putative cDNA clones for this enzyme were isolated. The longest of the cDNA clones has an insert of approximately 3 kb, and the complete nucleotide sequence was determined. Because this clone is missing the initiation codon and nucleotides corresponding to the leader peptide, the mRNA 5'-end sequence was determined by PCR (polymerase chain reaction) amplification and cycle sequencing. The sequence of the encoded protein from positions 23 to 35 is identical to the NH2-terminal sequence of one of the beta-N-acetylglucosaminidases isolated from pharate pupal molting fluid. The amino acid sequence is similar to those of silkworm, human, mouse, bacterial, and several other beta-N-acetylglucosaminidases. Two highly conserved regions in the amino acid sequence were found in all members of this family. Southern blot analysis suggested that the number of genes in the Manduca genome closely related to the cDNA clone may be as few as one. The beta-N-acetylglucosaminidase gene is expressed most abundantly in epidermal and gut tissues on days 6 and 7 of fifth instar larvae. Injection of 20-hydroxyecdysone induced expression of the beta-N-acetylglucosaminidase gene, whereas topical application of the juvenile hormone analog, fenoxycarb, suppressed the inductive effect of molting hormone.
Insect Biochem Mol Biol 1996 May
PMID:Cloning, expression, and hormonal regulation of an insect beta-N-acetylglucosaminidase gene. 876 62

We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.
Hum Mol Genet 1996 Jan
PMID:Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases. 878 34

Although the neuronal ceroid-lipofuscinoses (NCLs) are often referred to as lysosomal storage disorders, information on brain lysosomal hydrolases in NCLs is not available. We have determined the specific activities of several acid hydrolases in postmortem brain gray matter of infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL) forms of NCL, patients affected with other neurological disorders (ON), and normal controls. The specific activities of beta-hexosaminidase A and B were significantly high in JNCL gray matter, whereas in LINCL, the increase is significant only in beta-hexosaminidase compared to the controls. A significant increase in the activities of alpha-mannosidase, beta-glucuronidase, and acid phosphatase was also observed in LINCL and JNCL patients compared to the control values. beta-galactosidase activity was also found to be elevated in JNCL brains over the controls. In contrast, activities of beta-glucosidase and sialidase appeared to be lowered in INCL and LINCL. On the other hand, alpha-fucosidase, beta-mannosidase, and sulfatase were unaffected in NCLs brains. Thus, the present data indicate NCLs related abnormalities in some of the acid hydrolases in brain gray matter, which are primarily glycoproteins of lysosomal origin. These data in conjuction with the reported association of sphingolipid activator proteins (SAP) A and D and lysosomal glycoproteins with NCL storage bodies imply abberations in the glycoconjugate metabolism and lysosomal function.
Mol Chem Neuropathol
PMID:Brain lysosomal hydrolases in neuronal ceroid-lipofuscinoses. 897 94

beta-hexosaminidase is an essential lysosomal enzyme whose absence in man results in a group of disorders, the G(M2) gangliosidoses. beta-hexosaminidase activity is many times higher in the epididymis than in other tissues, is present in sperm, and is postulated to be required for mammalian fertilization. To better understand which cells are responsible for beta-hexosaminidase expression and how it is regulated in the male reproductive system, we quantitated the mRNA expression of the alpha- and beta-subunits of beta-hexosaminidase and carried out immunocytochemical localization studies of the enzyme in the rat testis and epididymis. beta-hexosaminidase alpha-subunit mRNA was abundant and differentially expressed in the adult rat testis and epididymis, at 13- and 2-fold brain levels, respectively. In contrast, beta-subunit mRNA levels in the testis and epididymis were 0.3- and 5-fold brain levels. During testis development from 7-91 postnatal days of age, testis levels of alpha-subunit mRNA increased 10-fold and coincided with the appearance of spermatocytes and spermatids in the epithelium; in contrast, beta-subunit mRNA was expressed at low levels throughout tests development. In isolated male germ cells, beta-hexosaminidase alpha-subunit expression was most abundant in haploid round spermatids, whereas the beta-subunit mRNA was not detected in germ cells. Within the epididymis both alpha- and beta-subunit mRNA concentrations were highest in the corpus, with 1.5-fold and 9-fold initial segment values, respectively. Light microscopic immunocytochemistry revealed that beta-hexosaminidase was localized to Sertoli cells and interstitial macrophages in the testis. In the epididymis, beta-hexosaminidase staining was most intense in narrow cells in the initial segment, principal cells in the caput and proximal corpus, and clear cells throughout the duct. Electron microscopic immunocytochemistry revealed that beta-hexosaminidase was predominantly present in lysosomes in Sertoli and epididymal cells. The cellular and regional specificity of beta-hexosaminidase immunolocalization suggest an important role for the enzyme in testicular and epididymal functions.
Mol Reprod Dev 1997 Mar
PMID:beta-Hexosaminidase immunolocalization and alpha- and beta-subunit gene expression in the rat testis and epididymis. 904 Nov 25

The phenotype of autosomal dominant polycystic kidney disease (ADPKD) is characterized by basement membrane abnormalities, hyperproliferation, and alterations in epithelial cell polarity. Since proteinases have been implicated in matrix degradation and growth factor activation, lysosomal enzymes were compared in normal and ADPKD tissues and cell cultures. Acidic proteolytic activity (azocasein) was reduced in ADPKD, and specific enzymatic assays detected disease-dependent decreases in the specific activities of beta-galactosidase, beta-hexosaminidase, and cathepsins, B, L, and H. Cathepsin D-specific activities were unchanged. Lucifer yellow fluorescence in ADPKD cells was consistent with an alteration in heterogeneity of lysosomal enzyme content in ADPKD rather than a decrease in total lysosomal number. Western analysis, metabolic labeling, and immunoprecipitation analysis confirmed decreases in the expression and synthesis of the major normal molecular immunoreactive species of beta-galactosidase and cathepsins B and H in ADPKD tissue and cells but no changes in cathepsin D. In addition, ADPKD-specific high-molecular-weight species of cathepsin H were seen and abnormal forms of cathepsin B and beta-galactosidase were common in ADPKD, suggesting abnormal molecular processing and posttranslational modifications. In addition, immunolocalization studies showed abnormal apical plasma-membrane localization of cathepsins B and H in ADPKD cyst epithelial cells, consistent with a protein sorting defect in ADPKD. Increased extracellular secretion of lysosomal enzymes was also measured in ADPKD cultured cells and in filter-grown epithelia shown to be predominantly directed to the basal compartment. These results demonstrate that lysosomal enzyme alterations in ADPKD may play a role in aberrant processing of the basement membrane. Alterations in the polarized secretion of lysosomal enzymes by ADPKD epithelia in vitro were also detected. Whereas all normal epithelia cells secreted lysosomal enzymes predominantly to the apical medium compartments, basally directed secretion was increased in all ADPKD epithelia and attained an overall reversal of polarity for cathepsins B + L. It is concluded that alterations in lysosomal enzyme function in ADPKD are the result of alterations in synthesis, molecular processing, and polarized secretion of specific enzymes and may have impact on proliferative and basement membrane abnormalities in this genetic disease. These results are consistent with a fundamental defect in protein processing sorting, and trafficking in ADPKD.
Biochem Mol Med 1997 Feb
PMID:Functional defects in lysosomal enzymes in autosomal dominant polycystic kidney disease (ADPKD): abnormalities in synthesis, molecular processing, polarity, and secretion. 906 78

Mycobacteria have the ability to persist within host phagocytes, and their success as intracellular pathogens is thought to be related to the ability to modify their intracellular environment. After entry into phagocytes, mycobacteria-containing phagosomes acquire markers for the endosomal pathway, but do not fuse with lysosomes. The molecular machinery that is involved in the entry and survival of mycobacteria in host cells is poorly characterized. Here we describe the use of organelle electrophoresis to study the uptake of Mycobacterium bovis bacille Calmette Guerin (BCG) into murine macrophages. We demonstrate that live, but not dead, mycobacteria occupy a phagosome that can be physically separated from endosomal/lysosomal compartments. Biochemical analysis of purified mycobacterial phagosomes revealed the absence of endosomal/lysosomal markers LAMP-1 and beta-hexosaminidase. Combining subcellular fractionation with two-dimensional gel electrophoresis, we found that a set of host proteins was present in phagosomes that were absent from endosomal/lysosomal compartments. The residence of mycobacteria in compartments outside the endosomal/lysosomal system may explain their persistence inside host cells and their sequestration from immune recognition. Furthermore, the approach described here may contribute to an improved understanding of the molecular mechanisms that determine the intracellular fate of mycobacteria during infection.
Mol Microbiol 1997 May
PMID:Isolation and characterization of the mycobacterial phagosome: segregation from the endosomal/lysosomal pathway. 917 48


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