Tay-Sachs Disease: Generalized Absence of a Beta-D-N-Acetylhexosaminidase Component
15 Aug 1969-Science (American Association for the Advancement of Science)-Vol. 165, Iss: 3894, pp 698-700
TL;DR: Two hexosaminidase components, separable by starch-gel electrophoresis and possessing both β-D-N-acetylglucosamininidase and β-O-NacetylgalactosaminIDase activity, are present in human tissues.
Abstract: Two hexosaminidase components, separable by starch-gel electrophoresis and possessing both beta-D-N-acetylglucosaminidase and beta-D-N-acetylgalactosaminidase activity, are present in human tissues. One of these, hexosaminidase component A, is absent in brain, liver, kidney, skin, cultured skin fibroblasts, blood plasma, and leukocytes from nine patients with Tay-Sachs disease. Hexosaminidase assay may facilitate the early diagnosis of individuals homozygous for Tay-Sachs disease.
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TL;DR: The leukocytes of male patients with Fabry's disease are deficient in α-galactosidase and the activity in the leukocyte of female carriers of the disease is 15 to 40 percent of the amount present in normalLeukocytes.
Abstract: The leukocytes of male patients with Fabry's disease are deficient in alpha-galactosidase. The alpha-galactosidase activity in the leukocytes of female carriers of the disease is 15 to 40 percent of the amount present in normal leukocytes. The activities of beta-galactosidase, beta-acetylgalactosaminidase, and beta-acetylglucosaminidase in the leukocytes of affected individuals are normal.
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TL;DR: A fluorometric method showed the activity of hexosaminidase A in human serum to be markedly deficient in serum specimens from nine patients with Tay–Sachs disease.
Abstract: A fluorometric method showed the activity of hexosaminidase A in human serum to be markedly deficient in serum specimens from nine patients with Tay–Sachs disease. Parents (obligate hetero...
377 citations
TL;DR: Investigation on the fate in vivo following intravenous injection of such protein-containing liposomes into rats showed that the bulk of liposomal radioactivity is removed from the blood within minutes, and Liposomes appear to be promising as a vehicle for the administration of enzymes and possibly also drugs to patients with storage diseases.
Abstract: [3H]Amyloglucosidase and 131I-labelled albumin were entrapped into liposomes (lipid spherules) composed of phosphatidyl choline, cholesterol and dicetyl phosphate (7:2:1 molar ratio). 131I-labelled albumin was also entrapped in [3H]cholesterol-liposomes.
Investigations on the fate in vivo following intravenous injection of such protein-containing liposomes into rats, showed that the bulk of liposomal radioactivity is removed from the blood within minutes. There is no measurable leakage of entrapped 131I-labelled albumin while liposomes are in the circulation.
Most of the removed liposomal radioactivity was recovered in the liver. Autoradiographic examination of the liver 3 min after injection of albumin-containing [3H]cholesterol-liposomes suggests that hepatocytes and probably Kupffer cells are involved in the uptake of liposomes. It appears that liposomes enter this tissue intact but subsequently liposomal membranes and entrapped protein are catabolized.
These catabolic processes are probably occurring in the liver lysosomes, as most of the liposomal radioactivity in this tissue was recovered in the mitochondrial-lysosomal fraction. Liposomes appear to be promising as a vehicle for the administration of enzymes and possibly also drugs to patients with storage diseases.
333 citations
References
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TL;DR: A simple procedure which enables the sample to be inserted into the gel without any supporting substance and evidence is obtained that genetic factors are concerned in the control of the 'post-albumins' of different persons.
Abstract: Experience with the method of zone electrophoresis in starch gels (Smithies, 1955) suggests that the resolution of protein components is lessened by the use of supporting substances (e.g. filter paper or starch grains) to prevent electro-decantation from occurring during the entry of migrating proteins into the gels. The present paper describes a simple procedure which enables the sample to be inserted into the gel without any supporting substance. Electro-decantation is prevented by carrying out the electrophoresis with the gel in a vertical position. The resolution of serum proteins obtainable in the gels is considerably improved, and the difficulties of obtaining reproducible results are reduced. Evidence is obtained with the new technique that genetic factors are concerned in the control of the 'post-albumins' of different persons. (A) General view of cover (underside) d
1,231 citations
TL;DR: The N-acetyl-β-glucosaminidase of human spleen has been separated by gel electrophoresis into two components, an acidic form A and a basic form B, and evidence is presented to indicate that the A form contains a number of sialic acid residues.
Abstract: 1. The N-acetyl-beta-glucosaminidase of human spleen has been separated by gel electrophoresis into two components, an acidic form A and a basic form B. 2. The two forms are readily separated on DEAE-cellulose and have been concentrated 50-fold and sevenfold respectively. 3. They show similar K(m) values towards 4-methylumbelliferyl N-acetyl-beta-d-glucosaminide, and have the same pH optima when compared in citrate, phosphate or acetate buffers. They are inhibited to a similar extent by acetate, heparin, N-acetylgalactosaminolactone, N-acetyl-beta-d-galactosamine and N-acetyl-beta-d-glucosamine. Specificity for C-4 orientation is not absolute and p-nitrophenyl beta-galactosaminide is also hydrolysed but at a rate only 11.6% of that for the corresponding glucosaminide. 4. N-Acetyl-beta-glucosaminidase B is stable over a wider pH range than is N-acetyl-beta-glucosaminidase A, and is less easily denatured by heat. 5. Tissue fractionation indicates that both the A and B forms are present in the lysosomal fraction, whereas the supernatant contains the A form only. 6. Evidence is presented to indicate that the A form contains a number of sialic acid residues.
438 citations
425 citations
TL;DR: A fluorometric method showed the activity of hexosaminidase A in human serum to be markedly deficient in serum specimens from nine patients with Tay–Sachs disease.
Abstract: A fluorometric method showed the activity of hexosaminidase A in human serum to be markedly deficient in serum specimens from nine patients with Tay–Sachs disease. Parents (obligate hetero...
377 citations
TL;DR: A profound deficiency of β-galactosidase activity was found in tissues from two patients with generalized gangliosidosis and this deficiency is demonstrated as a failure to cleave both p-nitrophenyl-β-D-Galactopyranoside and gangliosiside GM1 labeled with C14 in the terminal galactose.
Abstract: A profound deficiency (10- to 30-fold) of beta-galactosidase activity was found in tissues (liver, spleen, kidney, and brain) from two patients with generalized gangliosidosis; this deficiency is demonstrated as a failure to cleave both p-nitrophenyl-beta-D-galactopyranoside and ganglioside GM(1) labeled with C(14) in the terminal galactose. We believe that this enzymic defect is responsible for the accumulation of ganglioside GM(1) and is the fundamental enzyme defect in generalized gangliosidosis.
358 citations