Polysaccharides of connective tissue

M18. Meyer, K., Sulfated polysaccharides of connective tissues. Abst. Am. Chem. Sac. Meeting, Sept., 19S6, p. 15D. 

D-Glucuronic acid is widely distributed in both the plant and animal worlds. In humans, it is an important component of the acidic polysaccharides of connective tissues. The body also uses it to detoxify foreign phenols and alcohols. In the liver, these compounds are converted to glycosides of glucuronic acid (glucuronides), to be excreted in the urine. The intravenous anesthetic propofol (Problem 10.43), for example, is converted to the following water-soluble glucuronide and then excreted in the urine ... 

Dermatan sulfate, also termed chondroitin sulfate B, a related glycosaminoglycan constituent of connective tissue, was known to be composed of galactosamine and a uronic acid, originally believed to be glucuronic acid but then claimed to be iduronic acid based largely on color reactions and paper chromatography. However, the d or L-enantiomer status of the latter monosaccharide was not clear. Jeanloz and Stoffyn unequivocally characterized the monosaccharide as L-iduronic acid by consecutive desulfation, reduction, and hydrolysis of the polysaccharide, followed by isolation of the crystalline 2,3,4-tri-0-acetyl-l,6-anhydro-/ -L-idopyranose, which was shown to be identical to an authentic specimen synthesized from 1,2-0-isopropylidene-/ -L-idofuranose.34... 

The phosphate esters and, to lesser extent, the sulphate esters of monosaccharides are very important naturally occurring derivatives. Metabolism of carbohydrates involves the formation and interconversion of a succession of monosaccharides and their phosphate esters of which glucose-1-phosphate and fruc-tose-6-phosphate are important examples. The sulphate esters of monosaccharides or their derivatives (usually esterified at carbon 6) are found in several polysaccharides, notably chondroitin sulphate, which is a constituent of connective tissues. 

By constricting the vascular bed, such coadministered vasoactive excipients as epinephrine can reduce the rate of uptake from the SC sites (4a). By contrast, the excipient hyaluronidase breaks down the interstitial barrier by lysing hyaluronic acid, a polysaccharide that helps form the intercellular ground substance of connective tissue (4b). This in effect spreads the injected drug solution over a larger area of connective tissue, increasing the absorption surface, and thereby increasing both the volume that can normally be injected SC (Table 1) and the rate of uptake (6). 

Comper, W.D. and Laurent, T.C. (1978) Physiological function of connective tissue polysaccharides. Physiol. Rev., 58, 255-315. 

L. Roden Biosynthesis of connective tissue polysaccharides F. Shafizadeh Thermal reactions of cellulosic materials... 

Hyaluronic acid is a component of the extracellular ground substance which surrounds the collagen and elastin fibres and cells of connective tissue [64], It is a member of the group of polysaccharides isolated from vertebrate connective tissues which were formerly called mucopolysaccharides and are now more commonly referred to as glycosaminoglycans [65,66], Glycosaminoglycans commonly occur in vivo as proteoglycans. 

The extracellular matrix is the extracellular part of animal tissues that provides structural support it is the defining feature of connective tissue. Extracellular matrix includes the interstitial matrix and the basement membrane. Interstitial matrix is present between the cells (that is, in the intercellular spaces) it consists of polysaccharides and fibrous proteins, which act as a compression buffer. Basement membranes are sheet-like depositions of extracellular matrix on which various epithelial cells rest. 

In the fall of 1981, my wife, Janet Denlinger and I went to Paris to spend a year in Laszlo Robert and Jacqueline Labat-Robert s Biochemistry of Connective Tissue Laboratory at the Faculty of Medicine of the University of Paris. Laszlo and his wife Jacqueline are well-known researchers in the connective tissue field. The objective was for Janet to carry out research in the collaboration with the Roberts and write her doctoral thesis on the metabolism of hyaluronan in the vitreus and joint. She had already completed her course work at Columbia University. Professor Jean Montreuil, a polysaccharide chemist and Head of the Department of Chemistry at the University of Lille, along with Professor Robert, accepted the sponsorship of Janet s doctoral thesis which she presented in May of 1982 in French, earning a summa cum laude mention along with her degree. Her thesis work laid the foundation of our understanding of how hyaluronan is metabolized in the vitreus and joints of various animal species such as horses, rabbits and monkeys. 

The hydrodynamic resistance of solutions of connective-tissue polysaccharides has been measured by sedimentation techniques [9] the resistance is expressed as the hydraulic conductivity (k), which was defined in Equation 6-9 (Figure 6.8). This analysis permitted the identification of two different groups of polysaccharides those compounds containing Pi 4- and y6i 3-link-ages (such as chondroitan sulfate, keratan sulfate, and hyaluronate) had lower hydraulic resistance than compounds containing some fraction of... 

Comper, W.D. and O. Zamparo, Hydrodynamic properties of connective-tissue polysaccharides. Biochemical Journal, 1990, 269(3), 561-564. 

Senni, K., Gueniche, F., Bertaud, A. F., Tchen, S. I., Fioretti, F., Jouault, S. C., Durand, P., Guezennec, J., Godeau, G., and Letourneur, D. (2006). Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis. Arch. Biochem. Biophys. 445, 56-64. 

As noted above, the hydration, H, is linearly related to the end-to-end length, L, of the polysaccharide chains. We must then relate the swelling pressure, P, to the chemical potential of these chain molecules. For this, let us consider an osmotic experiment in which an excised piece of connective tissue is bathed in water. Mechanical equilibrium is maintained by the application of a pressure, P, on... 

It may also be noted that tearing of connective tissue causes the polysaccharide chains to break or to be pulled from the collagen fibers. This results in increased configurational entropy and increased osmotic activity. Thus, the injured connective tissue swells. 

Non-metallic trace nutrients include boron (for plants only), iodine and fluorine (for vertebrates), selenium, and silicon. Selenium forms an essential part of the important mammalian enzyme glutathione peroxidase which, in mammals, protects membranes from oxidation and is one of the microbiocidal enzymes in phagocytes (Stadtman, 1980). A selenium, iron, and molybdenum enzyme was described above under molybdenum . Silicon is thought to contribute to the architecture and resiliance of connective tissues of vertebrates. In rats, silicon is essential for growth and development. It seems to be present as a silanolate, with Si-O-R bridges to such polysaccharides as heparin and hyaluronic acid (Schwarz, 1973). 

In contrast to the neutral polysaccharides, the carbohydrate skeleton of heparin and mucopolysaccharides is based on an amino sugar uronic acid repeating unit. An important biological difference is that the neutral polysaccharides (glycogen, starch) are metabolic stores, the typical mucopolysaccharides (chondroitin sulfuric acids, keratin sulfate) are important structural materials of connective tissue, and the naturally occurring heparins and heparinoids are trace substances and appear to be associated with special cells. 

Mucopolysaccharides (MPS, also called glycosaminoglycans) are ani nic biopolymers widespread in animal tissues, especially in the intercellular matrix of connective tissues. These polysaccharides arc built up from amino sugars, either D-glucosamine or D-galactosamine, together with uronic acids, either D-glucuronic acid or L-iduronic acid and may have N-acetyl, 0- or N-sulfate groups. 

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