Glucocerebroside (also called glucosylceramide) is any of the cerebrosides in which the monosaccharide head group is glucose.
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Glucocerebroside (also called glucosylceramide) is any of the cerebrosides in which the monosaccharide head group is glucose.
In Gaucher's disease, the enzyme glucocerebrosidase is nonfunctional and cannot break down glucocerebroside into glucose and ceramide in the lysosome. [1] Affected macrophages, called Gaucher cells, have a distinct appearance similar to "wrinkled tissue paper" under light microscopy, because the substrates build-up within the lysosome. [2]
A lysosome is a single membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that digest 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 cell processes of secretion, plasma membrane repair, apoptosis, cell signaling, and energy metabolism.
Maltase is an informal name for a family of enzymes that catalyze the hydrolysis of disaccharide maltose into two simple sugars of glucose. Maltases are found in plants, bacteria, yeast, humans, and other vertebrates.
Gaucher's disease or Gaucher disease (GD) is a genetic disorder in which glucocerebroside accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase, which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages. Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Lysosomal storage diseases 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.
Cerebrosides (monoglycosylceramides) are a group of glycosphingolipids which are important components of animal muscle and nerve cell membranes.
β-Glucocerebrosidase is an enzyme with glucosylceramidase activity that cleaves by hydrolysis the β-glycosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism that is abundant in cell membranes. It is localized in the lysosome, where it remains associated with the lysosomal membrane. β-Glucocerebrosidase is 497 amino acids in length and has a molecular mass of 59,700 Da.
β-Glucosidase is an enzyme that catalyses the following reaction:
Ambroxol is a drug that breaks up phlegm, used in the treatment of respiratory diseases associated with viscid or excessive mucus. Ambroxol is often administered as an active ingredient in cough syrup.
Miglustat, sold under the brand name Zavesca among others, is a medication used to treat type I Gaucher disease and Pompe disease.
Ceramide glucosyltransferase is a glucosyltransferase enzyme involved in the production of glucocerebroside.
Ceramide glucosyltransferase is an enzyme that in humans is encoded by the UGCG gene.
Glucosidase, beta; acid, pseudogene, also known as GBAP, is a human gene.
Metaxin 1, also known as MTX1, is a protein which in humans is encoded by the MTX1 gene.
The Lactosylceramides, also known as LacCer, are a class of glycosphingolipids composed of a variable hydrophobic ceramide lipid and a hydrophilic sugar moiety. Lactosylceramides are found in microdomains on the plasma layers of numerous cells. Moreover, they are a type of ceramide including lactose, which is an example of a globoside.
Afegostat was an experimental drug for the treatment of certain forms of Gaucher's disease that was being developed by Amicus Therapeutics and Shire plc until a failed clinical trial in 2009 led to termination of its development. The substance was used in form of the tartrate.
Velaglucerase alfa, sold under the brand name Vpriv, is a medication used for the treatment of Gaucher disease Type 1. It is a hydrolytic lysosomal glucocerebroside-specific enzyme, which is a recombinant form of glucocerebrosidase. It has an identical amino acid sequence to the naturally occurring enzyme. It is manufactured by Shire plc.
In molecular biology, glycoside hydrolase family 30 is a family of glycoside hydrolases.
Eliglustat, sold under the brand name Cerdelga, is a medication used for the treatment of Gaucher's disease. It was discovered at the University of Michigan, developed by Genzyme Corp, and was approved by the FDA in August 2014. Commonly used as the tartrate salt, the compound is believed to work by inhibition of glucosylceramide synthase. According to an article in Journal of the American Medical Association the oral substrate reduction therapy resulted in "significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count" in untreated adults with Gaucher disease Type 1.
Dimitri Krainc is a Slovenian-born American physician-scientist who is the Aaron Montgomery Ward Professor and Chairman of the Ken & Ruth Davee Department of Neurology and Director of the Feinberg Neuroscience Institute and the Simpson Querrey Center for Neurogenetics at Northwestern University Feinberg School of Medicine. After completing his medical training at the University of Zagreb, Krainc spent more than two decades at the Massachusetts General Hospital and Harvard Medical School, where he completed his research and clinical training and served on faculty until relocating to Northwestern University in 2013. He has dedicated his scientific career to studying molecular pathways in the pathogenesis of neurodegeneration. Informed by genetic causes of disease, his work has uncovered key mechanisms across different neurodegenerative disorders that have led to pioneering design and development of targeted therapies. He has received numerous awards and recognitions for his work, including the Javits Neuroscience Investigator Award and the Outstanding Investigator award from NIH, and was elected to the Association of American Physicians, the National Academy of Medicine, and the National Academy of Inventors. He is the principal founding scientist of two biotech companies and serves as Venture Partner at OrbiMed. Krainc is President-elect of the American Neurological Association.
James Alan Shayman is an American physician scientist, nephrologist, and pharmacologist. He is Professor of Internal Medicine and Pharmacology and the Agnes C. And Frank D. McKay Professor at the Medical School of the University of Michigan. He also serves as a staff nephrologist at the Ann Arbor Veterans Administration Medical Center.
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