Clinical cases and Situational tasks

33. Some pathogens break down hyaluronic acid, releasing the enzyme hyaluronidase. Explain their advantages over the microorganisms lacking hyaluronidase activity.

Answer: Hyaluronidase allows certain pathogens to penetrate the body through mucous membranes and skin, causing hydrolysis (depolymerization) of hyaluronic acid, and thereby promotes their distribution in the human body. Determination of degradation products of connective tissue such as aminotsugars, glucuronic and sialic acids in blood and urine is widely used for indication of such microorganisms. Gram-positive bacteria produce a protective capsule, consisting from hyaluronic acid, which increases their pathogenicity.

34. Patient with burn disease is at the risk of formation of blood clots in blood vessels. What glycosaminoglycan may be used to prevent formation of blood clots?

Answer: Anticoagulant heparin belongs to derivatives of glycosaminoglycans. Its biochemical mechanism of action is achieved due to the fact that it binds to inhibitor of coagulation factor being antithrombin III. This leads to conformational changes of antithrombin III and thereby increasing of its resistance to thrombin. Preserved in such a way antithrombin prevents intravascular coagulation.

35. A patient revealed the fragility of blood vessel walls, increased bleeding, decreasing strength and elasticity of the skin. What component of the biosynthesis of connective tissue is affected? What is the most likely diagnosis?

Answer: Vitamin C plays the role of a coenzyme in hydroxylation of proline and lysine while protocollagen is converted to collagen (i.e. post-translational modification). The hydroxylation reaction is catalysed by lysyl hydroxylase (for lysine) and prolyl hydroxylase (for proline). This reaction is dependent on vitamin C, molecular oxygen and a-ketoglutarate. Hydroxyproline and hydroxylysine are essential for the collagen cross-linking and the strength of the fiber. In this way, vitamin C is necessary for maintenance of normal connective tissue and wound healing process. Deficiency of this vitamin leads to disruption of the formation of cross-linking, resulting in declining density and mechanical properties of collagen fibbers. Such symptoms are observed in scurvy.

36. The most abundant heteropolysaccharides of the connective tissue are the glycosaminoglycans. These molecules are long unbranched polysaccharides containing a repeating disaccharide unit. Indicate the following glycosaminoglycans:

Answer: a – hyaluronic acid, b – dermatan sulfate, c – chondroitin 4-sulfate, d – chondroitin 6-sulfate, e – keratan sulfate, f – heparin.