Characterization of two mannose-containing oligosaccharides isolated from the urine of patients with mannosidosis

Nordén, Nils E.; Lundblad, Arne; Svensson, Sigfrid; Autio, S.

doi:10.1021/bi00702a006

Cited by 91 publications

(30 citation statements)

References 18 publications

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“…Since the initial description of mannosidosis in 1967 (14), the biochemistry of this disorder has been characterized in several laboratories (1)(2)(3)(9)(10)(11)(12)(13)(14)(15)(16)(17). Heterogeneity has been observed in both the clinical severity and the biochemistry of this entity.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, this deduction is based on in vitro studies using a synthetic substrate. The observation that Znf+ causes a 40% stimulation of acidic a-mannosidase activity in the patients' cells agrees with previous findings and may be of significance in the treatment of such cases.Mannosidosis, a deficiency of the acidic form of a-mannosidase (EC 3.3.1.24) (14, 15), results in the accumulation of mannose-rich glycosylated compounds in the lysosomes of various tissues (1,12,15) and the excretion of similar compounds in the urine (13,17,18). Clinically, the disorder presents with mildly coarse facies, mild hepatosplenomegaly, skeletal changes, and psychomotor retardation.…”

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confidence: 99%

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A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

Bach

Kohn

Lasch³

et al. 1978

Pediatr Res

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SummaryA partial deficiency of a-mannosidase was found in cultured skin fibroblasts, serum, and extracts of leukocytes in two siblings with mild mental retardation, delayed speech, a suggestion of coarse or full facies, and limited mobility of the large joints. All other lysosomal enzymes tested were within the normal range. Their father demonstrated intermediate a-mannosidase activity. The addition of 2 mM Zn++ caused a 40% increase of the amannosidase activity in cell extracts of both patients and control subjects. pH profiles and Cellogel electrophoresis of the patients' cells indicated 20% residual activity of the acidic a-mannosidase isoenzyme (pH optimum at 4.0), whereas the activity of the isozyme with pH optimum of 6.0 was normal. Increasing substrate concentration (1-10 mM) demonstrated a 4to 5-fold increase in the a~~a r e n t K, of the acidic a-mannosidase in the patients' fibrobiasts. This residual activity, however, was apparently not sufficient for the normal catabolism of mannose-containing molecules, since electron microscopic examination of the culture; fibroblasts demonstrated numerous lysosomal storage bodies. SpeculationThis family supports the concept that mannosidosis is not a homogeneous syndrome but manifests clinical as well as biochemical heterogeneity. The partial activity of acidic a-mannosidase observed in the cultured fibroblasts (approximately 20%) was insufficient for normal catabolism and allows accumulation of amannoside-containing substrates leading to the abnormal phenctype. Nevertheless, this deduction is based on in vitro studies using a synthetic substrate. The observation that Znf+ causes a 40% stimulation of acidic a-mannosidase activity in the patients' cells agrees with previous findings and may be of significance in the treatment of such cases.Mannosidosis, a deficiency of the acidic form of a-mannosidase (EC 3.3.1.24) (14, 15), results in the accumulation of mannose-rich glycosylated compounds in the lysosomes of various tissues (1,12,15) and the excretion of similar compounds in the urine (13,17,18). Clinically, the disorder presents with mildly coarse facies, mild hepatosplenomegaly, skeletal changes, and psychomotor retardation. Human a-mannosidase is separable into two distinct isoenzymes in fibroblasts (16) and three distinct isoenzymes in liver (7). In the liver, two isoenzymes, supposedly lysosomal, have acidic optimal activity (pH 4.0-4.5), whereas the third, a nonlysosomal component, is optimally active at pH 6.0 (7). Patients with mannosidosis demonstrate either a complete deficiency or reduced activity of the acidic isoenzymes. Structural changes in the acidic isoenzyme demonstrate a 25-to 50-fold increase in apparent K, values and high susceptibility to heat inactivation 10 (4, 6, 8), whereas neutral a-mannosidase is normal (7, 11). The normal neutral a-mannosidase activity may explain the differing residual enzyme activities in various tissues of these patients. We wish to describe a family whose clinical and biochemical findings suggest a new variant of ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

Bach

Kohn

Lasch³

et al. 1978

Pediatr Res

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“…Analysis of the glycosphingolipids revealed a normal pattern (21). No evidence for mannoglycolipids was obtained, and individual glycolipids were not labeled to any significant (14,31,32) separable by DEAE-cellulose chromatography. In mannosidosis liver, the A and B forms (optimum pH 4.4) were shown to be absent, and the residual activity was due to the presence of the C form (optimum pH 6.0) in normal amounts.…”

Section: Resultsmentioning

confidence: 91%

Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency.

Tsay¹,

Dawson²,

Matalon³

1975

J. Clin. Invest.

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A B S T R A C T Patients with mannosidosis, an inherited deficiency of lysosomal a-mannosidase, accumulate large amounts of mannose-rich oligosaccharides (the "core" of the carbohydrate units of many glycoproteins) in brain and liver and excrete these partial degradation products in their urine. A profound a-mannosidase deficiency was demonstrated in fibroblasts cultured from a skin biopsy obtained from a child with mannosidosis. Further, abnormal glycopeptides rich in mannose and similar to oligosaccharides found in the patient's urine were isolated from fibroblast extracts by a variety of chromatographic procedures and by virtue of their binding to a concanavalin A-Sepharose 4B

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“…The structures of these oligosaccharides have been established** [5,6]. Bacterial growth was prevented by the addition of phenyl mercuric nitrate (final dilution 1:50000).…”

Section: Methodsmentioning

confidence: 99%

Mannosidosis in angus cattle: Partial characterization of two mannose containing oligosaccharides

et al. 1973

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Characterization of two mannose-containing oligosaccharides isolated from the urine of patients with mannosidosis

Cited by 91 publications

References 18 publications

A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency.

Mannosidosis in angus cattle: Partial characterization of two mannose containing oligosaccharides

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