Mucopolysaccharides, biosynthesis

Wolf, G. Vitamin A in adrenal hormone and mucopolysaccharide biosynthesis. Amer. J. din. Nutr. 9, 36-42 (1961)... 

The existence of biologically active metabolites of retinoic acid has been reported. Krishnamurthy et al. (1963) detected a fat-soluble metabolite of retinoic acid, which displayed biological activity in a rat curative assay, in the liver of chicks administered a 10-mg oral dose of the parent retinoid. Similarly, Wolf et al. (1963) reported that an intestinal metabolite, isolated from retinoid-deficient rats injected with labeled retinoic acid, was active in restoring to normal levels the mucopolysaccharide biosynthesis in retinoid-deficient rat intestinal cell-free particle suspensions. The same laboratory also described a decarboxy-lated metabolite of both retinol and retinoic acid that was isolated from the intestine of retinoid-deficient rats administered retinol or retinoic acid. This compound, which appeared to have both carboxyl and hydroxyl functional groups, was biologically active in a growth assay (Yagishita et al., 1964). In... 

Several acidic NAA have been shown O to Inhibit nlcotlnate phospho-rlbosyl transferase in human platelet lysate by reversible competition with nicotinic acid. The resulting suppression of nicotinamide adenine dl-nucleotlde biosynthesis may Inhibit mucopolysaccharide biosynthesis and reduce the Inflansnatory response. 

The dermis contains several types of cells, including fibroblasts, fat cells, macrophages, histiocytes, mast cells, and cells associated with the blood vessels and nerves of the skin. The predominant cell is the fibroblast, which is associated with biosynthesis of the fibrous proteins and ground substances such as hyaluronic acid, chondroitin sulfates, and mucopolysaccharides. 

It comes as no great surprise that trace elements may affect the growth and development of bone. Trace element deficiences profoundly alter hone metabolism in animals either directly or indirectly (3). The absence of a trace element in the diet can lead to inefficient functioning of a specific enzyme or enzymes that require the transition element as a cofactor. An example of this is the role of Cu and iron (Fe) in the cross-linking of collagen and elastins (4-9). The participation of Mn in the biosynthesis of mucopolysaccharides (10-12) is another example. Zn deficiency causes a reduction in osteoblastic activity, collagen and chondroitin sulfate synthesis and alkaline phosphatase activity (13-16). 

The mechanism whereby the backbone chains of the mucopolysaccharides are elaborated is at present unknown. At least two possible sequences in the biosynthesis could involve stepwise addition of either (1) (alternately) amino sugar and uronic acid or (2) initially formed disaccharide units which may contain a hexuronic or hexosaminic linkage. It is, however, clear that, at this point, a tremendous gap in our knowledge of heparin and other mucopolysaccharides exists. 

This mucopolysaccharide, possessing a strueture similar to those of chondroitin 4- and 6-sulfates but with a small content of sulfate, was isolated from bovine cornea (M16). Chondroitin resembles hyaluronic acid in its rate of hydrolysis by testicular and bacterial hyaluronidases, but was differentiated from hyaluronic acid ([a]n —65° to — 78°) by its optical rotation ( [o]d — 21°). Its structural similarity to chondroitin 4- and 6-sulfates was indicated by the fact that chondrosine was released in high yield on controlled, acidic hydrolysis (D3). The isolation of this mucopolysaccharide is of particular interest since it may be a precursor in the biosynthesis of chondroitin 4- and 6-sulfates. 

Schiller, S., and Doifman, A., The biosynthesis of mucopolysaccharides in the skin of alloxan-diabetic rats. Biochim. Biophys. Acta 16, 304-305 (1955). 

Hyaluronic acid is the only heteroglycan whose biosynthesis has been examined in detail. Since aminodeoxy sugar units are present, the polysaccharide is an aminodeoxypolysaccharide or, as it is more commonly termed, a mucopolysaccharide. Hyaluronic acid is a copolymer of two sugar units which alternate in a linear chain, and hence it may also be classified as a diheteroglycan. ... 

The biochemical properties of chloroquine and related anti-malarials have been exeonined further. In addition to its inhibition of the biosynthesis of sulfated mucopolysaccharides, chloroquine inhibits irreversibly an autolytic enzyme from bovine cartilage and a rat skin collagenase (at 10 mM). Like hydrocortisone, it inhibits chemotaocis of leukocytes and, to a lesser extent, the phagocytosis process.It also stabilizes lysosomal membranes in vitro. Potential "anti-degenerative" activity is clearly suggested by these properties, but unfortunately the well-known retinopathic effect is further complicated by a delayed symptom. 

Indomethacin also inhibits the motility of polymorphonuclear leukocytes and depresses the biosynthesis of mucopolysaccharides. It also may have a direct, cyclooxygenase-independent vasoconstrictor effect. Observational studies have raised the possibility that indomethacin may increase the risk of myocardial infarction and stroke, but controlled clinical trials to address this hypothesis have not been performed. 

The search for new and effective treatment modalities requires the availability of adequate screening tests. Although no model adequately reflects the events that occur in human arthritic conditions, several in vivo and in vitro assays are used. The most common in vivo animal assays measure the ability of anti-inflammatory drugs to inhibit edema induced in the rat paw by carrageenan (a mucopolysaccharide derived from a sea moss of the Chondrus species), to inhibit adjuvant arthritis in rats induced by Mycobacterium butyricum or M. tuberculosis, to inhibit granuloma formation usually induced by the implantation of a cotton pellet beneath the abdominal skin of rats, or to inhibit erythema of guinea pig skin as a result of exposure to ultraviolet radiation. In vitro techniques include the ability of NSAIDs to stabilize erythrocyte membranes or, more commonly, to inhibit the biosynthesis of prostaglandins, particularly in cultured human synoviocytes and chondrocytes, and monocyte culture fluid stimulated bovine synoviocytes and chondrocytes. 

Olsson, I., Gardell, S., and Thunell, S., Biosynthesis of glycosaminoglycans (mucopolysaccharides) in human leukocytes. Biochim. Biophys. Acta 165, 309-323 (1968). 

T6. Thomas, D. B., and Pasternak, C. A., Vitamin A and the biosynthesis of sulphated mucopolysaccharides. Experiments with rats and cultured neoplastic mast cells. Biochem. J. Ill, 407 12 (1969). 

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