The INDIVIDUALIST

A Wiki about biochemical individuality

Glycomics

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Description

Mucins are a family of large, heavily glycosylated proteins. Although some mucins are membrane-bound due to the presence of a hydrophobic membrane-spanning domain that favors retention in the plasma membrane, the concentration here is on those mucins that are secreted on mucosal surfaces and saliva.

Mucin genes encode mucin monomers that are synthesized as rod-shape apomucin cores that are post-translationally modified by exceptionally abundant glycosylation. Two distinctly different regions are found in mature mucins:

  • The amino- and carboxy-terminal regions are very lightly glycosylated, but rich in cysteines, which are likely involved in establishing disulfide linkages within and among mucin monomers.
  • A large central region formed of multiple tandem repeats of 10 to 80 residue sequences in which up to half of the amino acids are serine or threonine. This area becomes saturated with hundreds of O-linked oligosaccharides. N-linked oligosaccharides are also found on mucins, but much less abundantly.

The dense "sugar coating" of mucins gives them considerable water-holding capacity and also makes them resistant to proteolysis, which may be important in maintaining mucosal barriers.

Mucins are secreted as massive aggregates by prostaglandins with molecular masses of roughly 1 to 10 million Da. Within these aggregates, monomers are linked to one another mostly by non-covalent interactions, although intermolecular disulfide bonds may also play a role in this process. At least 19 human mucin genes have been distinguished by cDNA cloning--MUC1, 2, 3A, 3B, 4, 5AC, 5B, 6-9, 11-13, and 15-19. The major secreted airway mucins are MUC5AC and MUC5B, while MUC2 is secreted mostly in the intestine but also in the airway.

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The digestive tract (mouth, throat, stomach, intestines etc.) can be thought of as being semi-permeable, that is, they selectively allow substances to pass through in both directions (digestion to blood, blood to digestion). The gut is both absorptive and secretory. Each section of the gut is tailored for special functions. Just as there are appropriate mechanisms for transferring substances through the gut membrane, there are many mechanisms designed to restrict entry. Perhaps the most important of these is mucus.

Mucus is a complex mixture of proteins and carbohydrates secreted by mucus cells located within the gut wall. There is tremendous variation in the types of mucus produced in each separate part of the body and even wider differences in mucus composition between the various species (sheep, dog, mouse, etc.). The physical properties of mucus include low solubility, high viscosity, elasticity and adhesiveness, making it ideal for protecting the delicate tissue structures of the gut.

High molecular weight glycoproteins, mucins, usually contain greater than 50% carbohydrate in the form of neutral and acidic oligosaccharide chains. These units may contain galactose, fucose, N-acetylgalactosamine, N-acetylglucosamine and sialic acids. What is especially interesting about the mucin glycoproteins is the correlation with the ABO antigen system. Additionally the MN antigens usually determine which particular sialic acid residues predominate.

Discussion

  • Mucins are major glycoprotein components of mucus, covering the luminal surfaces of epithelial respiratory, gastrointestinal and reproductive tracts.
  • Aberrations in mucins and other cell surface carbohydrates are a universal characteristic of the malignant transformation of cells. Are responsible for altered cell adhesion or metastasis and to the avoidance of immunological defense.
  • Comprise peripheral structures representing blood group antigens as well as core structures such as Tn and T and their sialylated counterparts, sialyl Tn and sialyl T.

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