12.8.4: Glycation and Heteropolysaccharides
- Page ID
- 335358
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Endogenous glycation, on the other hand, arises with a frequency that is proportional to the concentration of free sugar in the body. These occur most frequently with fructose, galactose, and glucose in that decreasing order and are detected in the bloodstream. Both proteins and lipids can be glycated and the accumulation of endogenous advanced glycation endproducts (AGEs) is associated with Type 2 diabetes, as well as in increases in cardiovascular disease (damage to endothelium, cartilage, and fibrinogen), peripheral neuropathy (attack of myelin sheath), and deafness (loss of myelin sheath).
The formation of AGEs increases oxidative stress, but is also thought to be exacerbated by it. Increased oxidative stress, in turn causes additional harm. Damage to collagen in blood cells causes them to stiffen and weaken and is a factor in hardening of the arteries and formation of aneurysms, respectively. One indicator of diabetes is increased glycation of hemoglobin in red blood cells, since circulating sugar concentration are high in the blood of diabetics. Hemoglobin glycation is measured in testing for blood glucose control in diabetic patients.
Heteropolysaccharides
Many polysaccharides consist of repeating dissacharides units. Agarose, a polymer of a disaccharide repeat of (1-->3)-β-D-galactopyranose-(1 --> 4)-3,6-anhydro-α-L-galactopyranose, is often used for a gelable solid phase for electrophoresis of nucleic acid and as a component of chromatography beads. A major class of polysaccharides with dissacharide repeats include the following glycosaminoglycans (GAGs), all which contain one amino sugar in the repeat and in which one or both of the sugars contain negatively charged sulfate or carboxyl groups. The extent and position of sulfation varies widely between and within GAGs.
GAGs are found in the vitreous humor of the eye and synovial fluid of joints, and in connective tissue like tendons, cartilage, etc, as well as skin. They are found in the extracellular matrix and are often covalently attached to proteins to form proteoglycans.
Figure: Glycosaminoglycans
Function in skin
Hyaluronic acid is a major component of skin and has functions in tissue repair. With exposure to excess UVB radiation, cells in the dermis produce less hyaluronan and increase its degradation.
For some cancers the plasma level of hyaluronic acid correlates with malignancy. Hyaluronic acid levels have been used as a marker for prostate and breast cancer and to follow disease progression. The compound can to used to induce healing after cataract surgery. Hyaluronic acid is also abundant in the granulation tissue matrix that replaces a fibrin clot during the healing of wounds. In wound healing, it is thought that large polymers of hyaluronic acid appear early and they physically make room for white blood cells to mediate an immune response.
