Glycoproteinosis

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Glycoproteinosis
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Glycoproteinosis are lysosomal storage diseases [1] affecting glycoproteins, resulting from defects in lysosomal function. The term is sometimes reserved for conditions involving degradation of glycoproteins. [2]

Lysosomal storage disease inherited metabolic disorder that involve an abnormal accumulation of substances inside the lysosome resulting from defects in lysosomal function

Lysosomal storage diseases are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective, because of a mutation, the large molecules accumulate within the cell, eventually killing it.

Lysosome small lytic vacuole with cell cycle-independent morphology, found in most animal cells; contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6

A lysosome is a membrane-bound organelle found in many animal cells and most plant cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane proteins, and its lumenal proteins. The lumen's pH (~4.5–5.0) is optimal for the enzymes involved in hydrolysis, analogous to the activity of the stomach. Besides degradation of polymers, the lysosome is involved in various cell processes, including secretion, plasma membrane repair, cell signaling, and energy metabolism.

Contents

Types

Post-translational modification covalent and generally enzymatic modification of proteins during or after protein biosynthesis

Post-translational modification (PTM) refers to the covalent and generally enzymatic modification of proteins following protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signaling, as for example when prohormones are converted to hormones.

Mucolipidosis lipid storage disease that is characterized by increased storage of carbohydrates and lipids

Mucolipidosis (ML) is a group of inherited metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cells.

Glycoprotein protein with oligosaccaride modifications

Glycoproteins are proteins which contain oligosaccharide chains (glycans) covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated.

Another type, recently characterized, is galactosialidosis. [3]

Galactosialidosis rare disease

Galactosialidosis is a lysosomal storage disease. This condition is rare and most cases have been in the juvenile/adult group of patients. An infantile form has been described.

Related Research Articles

Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid. Sialic acids are found widely distributed in animal tissues and to a lesser extent in other organisms, ranging from fungi to yeasts and bacteria, mostly in glycoproteins and gangliosides. That is because it seems to have appeared late in evolution. However, it has been observed in Drosophila embryos and other insects and in the capsular polysaccharides of certain strains of bacteria. Generally, plants do not contain or display sialic acids. In humans the brain has the highest sialic acid concentration, where these acids play an important role in neural transmission and ganglioside structure in synaptogenesis. In general, the amino group bears either an acetyl or a glycolyl group, but other modifications have been described. These modifications along with linkages have shown to be tissue specific and developmentally regulated expressions, so some of them are only found on certain types of glycoconjugates in specific cells. The hydroxyl substituents may vary considerably; acetyl, lactyl, methyl, sulfate, and phosphate groups have been found. The term "sialic acid" was first introduced by Swedish biochemist Gunnar Blix in 1952.

Sialidosis Lysosomal storage disease

Mucolipidosis type I or sialidosis is an inherited lysosomal storage disease that results from a deficiency of the enzyme alpha-N -acetyl neuraminidase (sialidase). The lack of this enzyme results in an abnormal accumulation of complex carbohydrates known as mucopolysaccharides, and of fatty substances known as mucolipids. Both of these substances accumulate in bodily tissues.

Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme.

Alpha-galactosidase protein-coding gene in the species Homo sapiens

Alpha-galactosidase is a glycoside hydrolase enzyme that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. Glycosidase is an important class of enzyme catalyzing many catabolic processes, including cleaving glycoproteins and glycolipids, and polysaccharides. Specifically, α-GAL catalyzes the removal of the terminal α-galactose from oligosaccharides.

Acid alpha-glucosidase protein-coding gene in the species Homo sapiens

Acid alpha-glucosidase, also called α-1,4-glucosidase and acid maltase, is an enzyme that helps to break down glycogen in the lysosome. It is functionally similar to glycogen debranching enzyme, but is on a different chromosome, processed differently by the cell and is located in the lysosome rather than the cytosol. In humans, it is encoded by the GAA gene. Errors in this gene cause glycogen storage disease type II.

Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation channel, mucolipin1. These mutations disrupt cellular functions and lead to a neurodevelopmental disorder through an unknown mechanism. Researchers dispute the physiological role of the protein product and which ion it transports.

Pseudo-Hurler polydystrophy Human disease

Pseudo-Hurler polydystrophy, also referred to as mucolipidosis III, is a lysosomal storage disease closely related to I-cell disease. This disorder is called Pseudo-Hurler because it resembles a mild form of Hurler syndrome, one of the mucopolysaccharide (MPS) diseases.

I-cell disease Human disease

Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II, is part of the lysosomal storage disease family and results from a defective phosphotransferase. This enzyme transfers phosphate to mannose residues on specific proteins. Mannose 6 phosphate serves as a marker for them to be targeted to lysosomes within the cell. Without this marker, the proteins are instead excreted outside the cell—the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances in various tissues throughout the body. As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells". These cells can be identified under the microscope. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood.

Mannose 6-phosphate chemical compound

Mannose-6-phosphate (M6P) is a molecule bound by lectin in the immune system. M6P is converted to fructose 6-phosphate by mannose phosphate isomerase.

Cathepsin A protein-coding gene in the species Homo sapiens

Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.

N-acetylglucosamine-1-phosphate transferase is a transferase enzyme.

NEU1 protein-coding gene in the species Homo sapiens

Sialidase 1 , also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene.

Beta-mannosidosis lysosomal storage disease that has material basis in deficiency of the beta-A-manosidase enzyme resulting in the disruption of N-linked glycoprotein oligosaccharide catabolism.

Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency, is a disorder of oligosaccharide metabolism caused by decreased activity of the enzyme beta-mannosidase. This enzyme is coded for by the gene MANBA, located at 4q22-25. Beta-mannosidosis is inherited in an autosomal recessive manner. Affected individuals appear normal at birth, and can have a variable clinical presentation. Infantile onset forms show severe neurodegeneration, while some children have intellectual disability. Hearing loss and angiokeratomas are common features of the disease.

Schindler disease Rare congenital metabolic disorder in humans.

Schindler disease, also known as Kanzaki disease and alpha-N-acetylgalactosaminidase deficiency is a rare disease found in humans. This lysosomal storage disorder is caused by a deficiency in the enzyme alpha-NAGA (alpha-N-acetylgalactosaminidase), attributable to mutations in the NAGA gene on chromosome 22, which leads to excessive lysosomal accumulation of glycoproteins. A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids throughout the body. This accumulation of sugars gives rise to the clinical features associated with this disorder. Schindler disease is an autosomal recessive disorder, meaning that one must inherit an abnormal allele from both parents in order to have the disease.

Substrate reduction therapy offers an approach to treatment of certain metabolic disorders, especially glycogen storage diseases and lysosomal storage disorders. In a storage disorder, a critical failure in a metabolic pathway prevents cellular breakdown and disposal of some large molecule. If residual breakdown through other pathways is insufficient to prevent harmful accumulation, the molecule accumulates in the cell and eventually interferes with normal biological processes. Examples of lysosomal storage disorders include Gaucher's disease, Tay–Sachs disease, and Sandhoff disease.

Kifunensine Alkaloid

Kifunensine is an alkaloid originally isolated from Kitasatosporia kifunense, an actinobacterium. It is a neutral, stable compound.

References

  1. ↑ Charles H. Rodeck; Martin J. Whittle (27 October 2008). Fetal medicine: basic science and clinical practice. Elsevier Health Sciences. pp. 362–. ISBN   978-0-443-10408-4 . Retrieved 3 November 2010.
  2. ↑ Robert V. Stick; Spencer J. Williams (2 December 2008). Carbohydrates: the essential molecules of life. Elsevier. pp. 402–. ISBN   978-0-240-52118-3 . Retrieved 3 November 2010.
  3. ↑ Bonten EJ, Wang D, Toy JN, et al. (June 2004). "Targeting macrophages with baculovirus-produced lysosomal enzymes: implications for enzyme replacement therapy of the glycoprotein storage disorder galactosialidosis". FASEB J. 18 (9): 971–3. doi:10.1096/fj.03-0941fje. PMID   15084520.
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