Mucopolysaccharide, 3 -incorporation

Reaction (1) is irreversible the enzyme galactokinase has been found in mammalian liver, brain, and erythrocytes, as well as in certain yeasts and other microorganisms. UDPGal, the main product of reaction (2), is the intermediate by means of which the body incorporates galactose into cerebrosides and, probably, other galactolipids, mucopolysaccharides, and lactose galactose-l-phosphate uridyl transferase occurs in the liver, to a lesser extent in red cells, and probably in other tissues. 

Acetamido-2-deoxy-D-glucose is a component of a mucopolysaccharide hyaluronic acid. It has been demonstrated, by PET imaging with the corresponding F labeled compound, that this glucose derivative is incorporated into the connective tissue at the interface of a tumor and healthy tissue. Thus, it can be used as a tumor label. 6-[ F]-6-Deoxy-L-ascorbic acid also deserves attention, as it maintains the antioxidant properties of ascorbic acid. Thus, it can be useful to smdy the biochemical... 

Both D-glucuronic acid and 2-amino-2-deoxy-D-glucose appear to be incorporated into the mucopolysaccharides through utilization of intact D-glucose, with prior or subsequent oxidation or amination, respectively. This has followed from tracer studies, using D-glucose-6-C" and D-glucose-... 

The possibility that insulin regulates utilization of D-glucose for the synthesis of mucopolysaccharides in the ground substance of connective tissues was explored by Schiller and Dorfman (S3). Incorporation of sodium acetate-C into hyaluronic acid and dermatan sulfate in the skins of alloxan-diabetic rats was found to be approximately one third of that in the skins of either normal or partially fasted animals. These data suggest that synthesis of connective tissue mucopolysaccharides is inhibited in insulin-deficient animals. 

C) Sulfation occurs before the monosaccharides are incorporated into the mucopolysaccharide chain... 

D. The mucopolysaccharides of proteoglycans contain long chains of repeating disaccharide units that are covalently linked to a protein. Sulfation occurs after the monosaccharides are incorporated into the mucopolysaccharide chain. Proteoglycans are degraded by lysosomal... 

In rheumatic disease, the main pathological manifestations appear in connective tissue, the chief constituents of which are collagen, elastin and mucopolysaccharides. The last, apart from hyaluronic acid and chondroitin of cornea, are all sulphate esters , the sulphate groups of which are in a dynamic state with a short biological half-life. The sulphate exchange is under enzymic control and can be decreased in vitro and in vivo by corticosteroids " . Bostrom and Mansson examined the effects of a number of salicylates on the incorporation of S into calf costal cartilage slices in vitro. 

Whitehouse , and Whitehouse and Bostrom investigated the incorporation of glucose- G, acetate- G and S04 into mucopolysaccharide sulphates, and the oxidation of glucose- G, acetate-pyruvate- C and octanoate- C in cartilage and cornea. The incorporation of the above substances is inhibited by salicylate, phenylbutazone and cinchophen, all of which have an immediate effect on the reaction, and by hydrocortisone and chloroquine which are effective only after a time lag of 1-2 hours. There seems to be some relationship between the inhibition of uptake by non-steroidal compounds and their anti-inflammatory activities. It is concluded that the drugs diminish anabolic reactions in connective tissue by inhibiting fundamental exergonic reactions. 

Vitamin A deficiency characteristically results in hypoplasia of mucus-secreting tissues and keratinizing metaplasia of epithelial surfaces (171). The inhibition of mucus secretion appears to be related to a defect in mucopolysaccharide synthesis which can be attributed to a diminished incorporation of sulfate into 3 -phosphoadenosine-5 -phosphosulfate (active sulfate) (172). The impaired synthesis of active sulfate can be demonstrated in cell-free colon preparations from vitamin A deficient rats and can be restored to normals by a metabolite of vitamin A. 

The keratinization of epithelial structures has long been recognized as a feature of vitamin A deficiency, but the biochemical and ultrastructural details of this lesion are poorly understood. Keratinization implies accumulation of keratin, an insoluble protein rich in cystine sulfhydryl linkages. The incorporation of methionine- S into the skin of vitamin A deficient rats is markedly increased (173), and the incorporation of inorganic S04, presumably into mucopolysaccharides, is decreased. There is also evidence for an increased conversion of cystine into inorganic sulfate (174), and the total cystine content of skin is depressed (175). 

The defect in mucopolysaccharide synthesis together with the increased incorporation of methionine sulfur and the decreased cystine content may reflect an increased epithelial cell turnover, as suggested by the hyperplastic mucosa and the masses of epithelial cells in the biliary tract, but the picture is not yet complete. In any case, it is clear that desquamated cells appear to be the most important factor in this form of cholelithiasis. The contribution of cellular debris to other types of gallstone formation has been discussed in previous sections. 

The mucopolysaccharide content of the costochondral cartilage and the skin of scorbutic guinea pigs is reduced 15-20%. In addition, the rate of sulfate incorporation is greatly reduced in the costochondral cartilage after cortisone administration, but is restored to normal by the addition of vitamin C. Finally, S-incorporation is also reduced in the healing wounds of scorbutic animals. 

Wolf and his associates [109, 110] studied the effect of vitamin A on mucus synthesis by investigating the effect of vitamin A on mucopolysaccharide synthesis by colon segments and colon homogenates of vitamin deficient rats. The incorporation of in the mucus polysaccharides of colon segments of vitamin deficient rats is about half of that observed in colon segments obtained from rats fed a diet containing vitamin A. The rate of incorporation into the deficient mucosa was restored to normal by adding vitamin A to the incubation medium. 

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