Lysosomal hydrolases: Conversion of acidic to basic forms by neuraminidase

Goldstone, Alfred; Konecny, Filip; Koenig, Harold

doi:10.1016/0014-5793(71)80667-1

Cited by 144 publications

(51 citation statements)

References 16 publications

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“…Our data do not allow distinction between difisolating the contribution of its individual components. ferent hypotheses on the structural relationship between the two enzymes, as, for example, the proposed existence of a common subunit shared by HexA and HexB (28) or the proposed conversion of HexB to HexA by the action of glycosyl transferases (29). However, our data indicate that a gene exists that is responsible for the expression of HexA, possibly either through a modification of hexosaminidase B or through an interaction with a HexB gene product.…”

Section: Resultsmentioning

confidence: 49%

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Human β-D- N -Acetylhexosaminidases A and B: Expression and Linkage Relationships in Somatic Cell Hybrids

Lalley

Rattazzi

Shows

1974

Proc. Natl. Acad. Sci. U.S.A.

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Knowledge of the genetic relationships between fl-D-N-acetylhexosaminidases A and B (EC 3.2.1.30) may help in understanding the hexosaminidase deficiency associated with GM2 gangliosidosis, a fatal lipid storage disease in man. Through the use of man-mouse somatic cell hybrids we have found that a gene involved in hexosaminidase A expression was linked to the genes coding for mannosephosphate isomerase and pyruvate kinase-3. The gene coding for hexosaminidase B was not linked to any of the genes coding for 25 enzyme markers tested. A combination of immunological and electrophoretic techniques was employed to identify human hexosaminidases A and B with certainty in cell hybrids. Discordant segregation of hexosaminidase A and hexosaminidase B in 60 clones indicated that the genes coding for their expression were not linked. However, hexosaminidase A was never expressed in cell hybrids in the absence of hexosaminidase B. This suggests that the gene responsible for the hexosaminidase A phenotype, linked to mannosephosphate isomerase and pyruvate kinase-3, requires the presence of the gene coding for hexosaminidase B for the expression of hexosaminidase A. These observations offer a genetic explanation for the biochemical and immunological relationships between hexosaminidases A and B and provide the framework for identifying the basic genetic defects responsible for GM2 gangliosidosis.

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Section: Resultsmentioning

confidence: 49%

“…Shows (1,3,19,27,29). Our data do not allow distinction between difisolating the contribution of its individual components.…”

Section: Resultsmentioning

confidence: 72%

Human β-D- N -Acetylhexosaminidases A and B: Expression and Linkage Relationships in Somatic Cell Hybrids

Lalley

Rattazzi

Shows

1974

Proc. Natl. Acad. Sci. U.S.A.

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“…nidase retards its mobility toward the anode but does not convert it to ARSB (25,29). The different physical-chemical characteristics of ARSA and ARSB and their distinct physiologic specificities suggest these enzymes are coded by different structural genes.…”

Section: Methodsmentioning

confidence: 99%

Lysosomal arylsulfatase deficiencies in humans: Chromosome assignments for arylsulfatase A and B

DeLuca

Brown

Shows

1979

Proc. Natl. Acad. Sci. U.S.A.

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form of MLD, has been described which is characterized by multiple sulfatase deficiencies (4). The simultaneous deficiency of arysulfatases A, B, and C and the steroid sulfatases raises the possibility that all share a common property. Interspecific somatic cell hybrids have been used to dissect genetic and structural components required for the final expression of enzymes and to characterize molecular defects in inherited deficiency diseases (8). We have used human-Chinese hamster hybrids to determine whether there exists a genetic or structural relationship between the lysosomal arylsulfatases and to map the structural genes associated with the enzyme deficiencies. We have demonstrated separate and independent chromosomal localization for their structural genes. ARSA segregated with mitochondrial aconitase (ACONM), whose structural gene has been assigned to chromosome 22 in humans (9, 10). ARSB segregated with fl-hexosaminidase B (HEXB), assigned to chromosome 5 (11, 12). Assignments of ARSA and ARSB to chromosomes 22 and 5, respectively, were confirmed by chromosome analysis. Independent segregation of the two lysosomal activities in somatic cell hybrids is compatible with their separate expression in single sulfatase deficiencies, as seen in MLD and MLS, and suggests genetic independence of the two diseases. The cell hybrid evidence excluded a common subunit for ARSA and ARSB as a possible explanation for their joint deficiency in the multiple sulfatase deficiency disorder. Taken together, this disorder and the gene assignment data suggest that an additional independent gene functions in affecting the expression of sulfatase activity in humans. MATERIALS AND METHODSParental Cells. Human fibroblast lines (13) for qell fusion were AlTr (X/5 translocation), DUV, JoVa, TS-495, and GM 1696 (14). Fresh human leukocytes used for fusion were ChDe and PeLa (13

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“…In serum, two forms (A and B) have been observed by Okada and O'Brien [22], three by Lowden and LaRamee [14], and four by Price and Dance [25]; two types have been detected in leukocytes and cultured fibroblasts [ l l , 23, 381, and two [32,471 or possibly three types [I21 in liver. Conversion from one form to another by treatment with neuraminidase [6,181 or by heating [25] has been reported.…”

Section: Enzyme Assaymentioning

confidence: 99%

“…I t has been suggested that the differences in chromatographic and electrophoretic properties of the major forms of hexosaminidases are due to differences in carbohydrate content [6,181 or indicate that both hexosaminidase A and B are multimers with at least one common subunit and a different subunit [3, 371. T h e latter theory has received strong support recently from immunochemical [26, 361 and cell hybridization studies [43]. Although the structure of the hexosaminidases in man is not known, the enzyme pattern in our patient shows that some degree of A activity alone is possible, analogous to B activity alone in Tay-Sachs disease.…”

Section: Enzyme Assaymentioning

confidence: 99%

A New Variant of Sandhoff's Disease

et al. 1974

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ExtractA 28-month-old Negro male with atypical Sandhoff's disease (GM2 gangliosidosis, type 2) is described. Clinical presentation closely resembled Sandhoff's disease. The appendiceal neuron cytoplasm was distended with periodic acid-Schiff (PAS)-positive material. Hepatic glycolipid N-acetylneuraminic acid was elevated 1.5-fold, chiefly because of increased GM2. Neutral glycolipid hexose was elevated twofold, mainly because of a component with globoside-like chromatographic properties. Unlike patients with Sandhops disease, the child had total 0-D-N-acetylhexosaminidase activity 20-24% of normal in serum and plasma and 7-1 1% of normal in leukocytes and cultured fibroblasts, but activity in liver (<2y0 of normal) was similar to that in Sandhoff's disease. In all tissues examined, >95% of the activity was heat denaturable, corresponding in electrophoretic mobility to the heat-denaturable component of normal tissues. The decrease in heat-denaturable activity with time and the pH optimum were similar in patient and control crude tissue preparations and partially purified preparations of plasma hexosaminidase A. In the child's mother, total hexosaminidase activity was approximately 50y0 of mean control values in serum, plasma, and leukocytes, and serum hexosaminidase A was relatively increased. This finding, together with the death of at least three other children in the kindred from an apparently phenotypically similar illness, indicates the inherited nature of the disorder. SpeculationAppreciable hexosaminidase activity in serum and plasma and its marked deficiency in liver suggest that the active form (or forms) in serum and plasma differ from those in solid tissues, and that the mutation in the case described has altered the hexosaminidases in a manner that virtually abolishes their activity in solid tissues but permits their partial activity in serum and plasma.

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Lysosomal hydrolases: Conversion of acidic to basic forms by neuraminidase

Cited by 144 publications

References 16 publications

Human β-D- N -Acetylhexosaminidases A and B: Expression and Linkage Relationships in Somatic Cell Hybrids

Human β-D- N -Acetylhexosaminidases A and B: Expression and Linkage Relationships in Somatic Cell Hybrids

Lysosomal arylsulfatase deficiencies in humans: Chromosome assignments for arylsulfatase A and B

A New Variant of Sandhoff's Disease

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