Gangliosidoses
A group of autosomal recessive lysosomal storage disorders marked by the accumulation of GANGLIOSIDES. They are caused by impaired enzymes or defective cofactors required for normal ganglioside degradation in the LYSOSOMES. Gangliosidoses are classified by the specific ganglioside accumulated in the defective degradation pathway.
Lipidoses
Hexosaminidase A
A mammalian beta-hexosaminidase isoform that is a heteromeric protein comprized of both hexosaminidase alpha and hexosaminidase beta subunits. Deficiency of hexosaminidase A due to mutations in the gene encoding the hexosaminidase alpha subunit is a case of TAY-SACHS DISEASE. Deficiency of hexosaminidase A and HEXOSAMINIDASE B due to mutations in the gene encoding the hexosaminidase beta subunit is a case of SANDHOFF DISEASE.
Hexosaminidase B
A mammalian beta-hexosaminidase isoform that is comprized of hexosaminidase beta subunits. Deficiency of hexosaminidase B due to mutations in the gene encoding the hexosaminidase beta subunit is a case of SANDHOFF DISEASE.
Hexosaminidases
Enzymes that catalyze the hydrolysis of N-acylhexosamine residues in N-acylhexosamides. Hexosaminidases also act on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES.
beta-N-Acetylhexosaminidases
A hexosaminidase specific for non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. It acts on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES. Two specific mammalian isoenzymes of beta-N-acetylhexoaminidase are referred to as HEXOSAMINIDASE A and HEXOSAMINIDASE B. Deficiency of the type A isoenzyme causes TAY-SACHS DISEASE, while deficiency of both A and B isozymes causes SANDHOFF DISEASE. The enzyme has also been used as a tumor marker to distinguish between malignant and benign disease.
Tay-Sachs Disease
An autosomal recessive neurodegenerative disorder characterized by the onset in infancy of an exaggerated startle response, followed by paralysis, dementia, and blindness. It is caused by mutation in the alpha subunit of the HEXOSAMINIDASE A resulting in lipid-laden ganglion cells. It is also known as the B variant (with increased HEXOSAMINIDASE B but absence of hexosaminidase A) and is strongly associated with Ashkenazic Jewish ancestry.
G(M2) Ganglioside
A glycosphingolipid that accumulates due to a deficiency of hexosaminidase A or B (BETA-N-ACETYLHEXOSAMINIDASES), or GM2 activator proteinM2 resulting in GANGLIOSIDOSES, heredity metabolic disorders that include TAY-SACHS DISEASE and SANDHOFF DISEASE.
Sandhoff Disease
An autosomal recessive neurodegenerative disorder characterized by an accumulation of G(M2) GANGLIOSIDE in neurons and other tissues. It is caused by mutation in the common beta subunit of HEXOSAMINIDASE A and HEXOSAMINIDASE B. Thus this disease is also known as the O variant since both hexosaminidase A and B are missing. Clinically, it is indistinguishable from TAY-SACHS DISEASE.
G(M2) Activator Protein
An essential cofactor for the degradation of G(M2)GANGLIOSIDE by lysosomal BETA-N-ACETYLHEXOSAMINIDASES. Genetic mutations resulting in loss of G(M2) activator protein are one of the causes of TAY-SACHS DISEASE, AB VARIANT.
Acetylglucosaminidase
A beta-N-Acetylhexosaminidase that catalyzes the hydrolysis of terminal, non-reducing 2-acetamido-2-deoxy-beta-glucose residues in chitobiose and higher analogs as well as in glycoproteins. Has been used widely in structural studies on bacterial cell walls and in the study of diseases such as MUCOLIPIDOSIS and various inflammatory disorders of muscle and connective tissue.
Interleukin-1beta
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
Chromosomes, Human, 4-5
Sphingolipid Activator Proteins
beta 2-Microglobulin
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Hymecromone
Isoenzymes
Gangliosidoses, GM2
A group of recessively inherited diseases characterized by the intralysosomal accumulation of G(M2) GANGLIOSIDE in the neuronal cells. Subtypes include mutations of enzymes in the BETA-N-ACETYLHEXOSAMINIDASES system or G(M2) ACTIVATOR PROTEIN leading to disruption of normal degradation of GANGLIOSIDES, a subclass of ACIDIC GLYCOSPHINGOLIPIDS.
Electrophoresis, Starch Gel
Amino Acid Sequence
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Receptors, Adrenergic, beta
Integrin beta3
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
Saposins
A group of four homologous sphingolipid activator proteins that are formed from proteolytic cleavage of a common protein precursor molecule referred to as prosaposin.
Chromosomes, Human, 13-15
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Macromolecular Substances
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Base Sequence
Lysosomes
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Receptors, Antigen, T-Cell, alpha-beta
Transforming Growth Factor beta
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Cells, Cultured
Isoelectric Focusing
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Electrophoresis, Polyacrylamide Gel
Hemoglobins, Abnormal
Mutation
Integrin alpha5beta1
An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.
Integrin beta4
Integrin beta Chains
Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.
Gangliosidosis, GM1
An autosomal recessive neurodegenerative disorder caused by the absence or deficiency of BETA-GALACTOSIDASE. It is characterized by intralysosomal accumulation of G(M1) GANGLIOSIDE and oligosaccharides, primarily in neurons of the central nervous system. The infantile form is characterized by MUSCLE HYPOTONIA, poor psychomotor development, HIRSUTISM, hepatosplenomegaly, and facial abnormalities. The juvenile form features HYPERACUSIS; SEIZURES; and psychomotor retardation. The adult form features progressive DEMENTIA; ATAXIA; and MUSCLE SPASTICITY. (From Menkes, Textbook of Child Neurology, 5th ed, pp96-7)