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Mannose 6-phosphate
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. M6P is a key targeting signal for acid hydrolase precursor proteins that are destined for transport to lysosomes. The M6P tag is added to such proteins in the ''cis''-Golgi apparatus. Specifically, in a reaction involving uridine diphosphate (UDP) and ''N''-acetylglucosamine, the enzyme N-acetylglucosamine-1-phosphate transferase catalyzes the ''N''-linked glycosylation of asparagine residues with M6P. Once appropriately marked with the M6P targeting signal, these proteins are moved to the ''trans''-Golgi network. There, the M6P moiety is recognized and bound by mannose 6-phosphate receptor (MPR) proteins at pH 6.5–6.7. The M6P-tagged lysosomal enzymes are shipped to the late endosomes via vesicular transport. Enzyme replacement therapy (ERT) for several lysosomal storage diseases relies on this pathway to efficiently direct syn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lectin
Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in recognition at the cellular and molecular level and play numerous roles in biological recognition phenomena involving cells, carbohydrates, and proteins. Lectins also mediate attachment and binding of bacteria, viruses, and fungi to their intended targets. Lectins are ubiquitous in nature and are found in many foods. Some foods, such as beans and grains, need to be cooked, fermented or sprouted to reduce lectin content. Some lectins are beneficial, such as CLEC11A, which promotes bone growth, while others may be powerful toxins such as ricin. Lectins may be disabled by specific mono- and oligosaccharides, which bind to ingested lectins from grains, legumes, nightshade plants, and dairy; binding can prevent their attachment to the carbohy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Asparagine
Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain carboxamide, classifying it as a polar (at physiological pH), aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it. It is encoded by the codons AAU and AAC. History Asparagine was first isolated in 1806 in a crystalline form by French chemists Louis Nicolas Vauquelin and Pierre Jean Robiquet (then a young assistant). It was isolated from asparagus juice, in which it is abundant, hence the chosen name. It was the first amino acid to be isolated. Three years later, in 1809, Pierre Jean Robiquet identified a substance from liquorice root with properties which he qualified as very similar to those of asparagine, and which Plisson identi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mannose 1-phosphate
Mannose 1-phosphate is a molecule involved in glycosylation. See also * Congenital disorder of glycosylation A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defect ... * Mannose-6-phosphate Organophosphates Monosaccharide derivatives {{organic-compound-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation are associated with mutations in enzymes involved in mannose metabolism. Mannose is not an essential nutrient; it can be produced in the human body from glucose, or converted into glucose. Mannose provides 2–5 kcal/g. It is partially excreted in the urine. Etymology The root of both "mannose" and "mannitol" is manna, which the Bible describes as the food supplied to the Israelites during their journey in the region of Sinai. Several trees and shrubs can produce a substance called manna, such as the "manna tree" ('' Fraxinus ornus'') from whose secretions mannitol was originally isolated. Structure Mannose commonly exists as two different-sized rings, the pyranose (six-membered) form and the furanose (five-membered) form. Eac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Insulin-like Growth Factor 2 Receptor
Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the ''IGF2R'' gene. IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the ''trans''- Golgi network. Structure The structure of the IGF2R is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-terminus on the cytoplasmic side of lipid membranes) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail. The extracellular domain consists of a small region homologous to the collagen-binding domain of fibronectin and of fifteen repeats of approximately 147 amino acid residues. Each of these repeats is homologous to the 157-residue extracytoplasmic domain of the mannose 6-phosphate receptor. Binding to IGF2 is mediated through one of the repeats, while tw ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
I-cell Disease
Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II (ML II), is part of the lysosomal storage disease family and results from a defective phosphotransferase (an enzyme of the Golgi apparatus). This enzyme transfers phosphate to mannose residues on specific proteins. Mannose-6-phosphate serves as a marker for proteins to be targeted to lysosomes within the cell. Without this marker, proteins are instead secreted outside the cell, which is 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 (e.g. oligosaccharides, lipids, and glycosaminoglycans) in various tissues throughout the body (i.e. fibroblasts). 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" seen microscopically. In addition, the defective lysosomal en ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lysosomal Storage Diseases
Lysosomal storage diseases (LSDs; ) are a group of over 70 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 due to a mutation, the large molecules accumulate within the cell, eventually killing it. Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar-containing proteins), or so-called mucopolysaccharides. Individually, lysosomal storage diseases occur with incidences of less than 1:100,000; however, as a group, the incidence is about 1:5,000 – 1:10,000. Most of these disorders are autosomal recessively inherited such as Niemann–Pick disease, type C, but a few are X-linked recessively inherited, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme Replacement Therapy
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. ERT is available for some lysosomal storage diseases: Gaucher disease, Fabry disease, MPS I, MPS II (Hunter syndrome), MPS VI and Pompe disease. ERT does not correct the underlying genetic defect, but it increases the concentration of the enzyme that the patient is lacking. ERT has also been used to treat patients with severe combined immunodeficiency (SCID) resulting from an adenosine deaminase deficiency (ADA-SCID). Other treatment options for patients with enzyme or protein deficiencies include substrate reduction therapy, gene therapy, and bone-marrow derived stem cell transplantation. History ERT was developed in 1964 by Christian de Duve and Roscoe Brady. Leading work was done on this subject at the Department of Physiology at the Univers ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endosomes
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. Function Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, low-density lipoprotein (LDL) is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL dissociates ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mannose 6-phosphate Receptor
The mannose 6-phosphate receptors (MPRs) are transmembrane glycoproteins that target enzymes to lysosomes in vertebrates. Mannose 6-phosphate receptors bind newly synthesized lysosomal hydrolases in the trans-Golgi network (TGN) and deliver them to pre-lysosomal compartments. There are two different MPRs, one of ~300kDa and a smaller, dimeric receptor of ~46kDa. The larger receptor is known as the cation-independent mannose 6-phosphate receptor ( CI-MPR), while the smaller receptor ( CD-MPR) requires divalent cations to efficiently recognize lysosomal hydrolases. While divalent cations are not essential for ligand binding by the human CD-MPR, the nomenclature has been retained. Both of these receptors bind terminal mannose 6-phosphate with similar affinity (CI-MPR = 7 μM, CD-MPR = 8 μM) and have similar signals in their cytoplasmic domains for intracellular trafficking. History Elizabeth Neufeld was studying patients who had multiple inclusion bodies present in their ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Moiety (chemistry)
In organic chemistry, a moiety ( ) is a part of a molecule that is given a name because it is identified as a part of other molecules as well. Typically, the term is used to describe the larger and characteristic parts of organic molecules, and it should not be used to describe or name smaller functional groups of atoms that chemically react in similar ways in most molecules that contain them. Occasionally, a moiety may contain smaller moieties and functional groups. A moiety that acts as a branch extending from the backbone of a hydrocarbon molecule is called a substituent or side chain, which typically can be removed from the molecule and substituted with others. Active moiety In pharmacology, an active moiety is the part of a molecule or ion – excluding appended inactive portions – that is responsible for the physiological or pharmacological action of a drug substance. Inactive appended portions of the drug substance may include either the alcohol or acid moiety of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
N-linked Glycosylation
''N''-linked glycosylation, is the attachment of an oligosaccharide, a carbohydrate consisting of several sugar molecules, sometimes also referred to as glycan, to a nitrogen atom (the amide nitrogen of an asparagine (Asn) residue of a protein), in a process called ''N''-glycosylation, studied in biochemistry. This type of linkage is important for both the structure and function of many eukaryotic proteins. The ''N''-linked glycosylation process occurs in eukaryotes and widely in archaea, but very rarely in bacteria. The nature of ''N''-linked glycans attached to a glycoprotein is determined by the protein and the cell in which it is expressed. It also varies across species. Different species synthesize different types of ''N''-linked glycan. Energetics of bond formation There are two types of bonds involved in a glycoprotein: bonds between the saccharides residues in the glycan and the linkage between the glycan chain and the protein molecule. The sugar moieties are linked t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
