Polysaccharides:- Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix

The extracellular space in the tissues of multicellular animals is filled with a gel-like material, the extracellular matrix, also called ground substance, which holds the cells together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells. The extracellular matrix is composed of an interlocking meshwork of heteropoly saccharides and fibrous proteins such as collagen, elastin, fibronectin, and laminin. These heteropolysaccharides, the glycosaminoglycans, are a family of linear polymers composed of repeating disaccharide units (Fig. 7–24). One of the two monosaccharides is always either N-acetylglucosamine or N-acetyl galactosamine; the other is in most cases a uronic acid, usually D-glucuronic or L-iduronic acid. In some glycosaminoglycans, one or more of the hydroxyls of the amino sugar are esterified with sulfate. The combination of sulfate groups and the carboxylate groups of the uronic acid residues gives glycosaminoglycans a very high density of negative charge. To minimize the repulsive forces among neighboring charged groups, these molecules assume an extended conformation in solution. The specific patterns of sulfated and nonsulfated sugar residues in glycosaminoglycans provide for specific recognition by a variety of protein ligands that bind electrostatically to these molecules. Glycosaminoglycans are attached to extracellular proteins to form proteoglycans (Section 7.3). The glycosaminoglycan hyaluronic acid (hyaluronate at physiological pH) contains alternating residues of D-glucuronic acid and N-acetylglucosamine (Fig. 7–24). With up to 50,000 repeats of the basic disaccharide unit, hyaluronates have molecular weights greater than 1 million; they form clear, highly viscous solutions that serve as lubricants in the synovial fluid of joints and give the vitreous humor of the vertebrate eye its jelly like consistency (the Greek hyalos means “glass”; hyaluronates can have a glassy or translucent appearance). Hyaluronate is also an essential component of the extracellular matrix of cartilage and tendons, to which it contributes tensile strength and elasticity as a result of its strong interactions with other components of the matrix. Hyaluronidase, an enzyme secreted by some pathogenic bacteria, can hydrolyze the glycosidic link ages of hyaluronate, rendering tissues more susceptible to bacterial invasion. In many organisms, a similar en zyme in sperm hydrolyzes an outer glycosaminoglycan coat around the ovum, allowing sperm penetration. Other glycosaminoglycans differ from hyaluronate in two respects: they are generally much shorter polymers and they are covalently linked to specific proteins (proteoglycans). Chondroitin sulfate (Greek chondros, “cartilage”) contributes to the tensile strength of cartilage, tendons, ligaments, and the walls of the aorta. Dermatan sulfate (Greek derma, “skin”) contributes to the pliability of skin and is also present in blood vessels and heart valves. In this polymer, many of the glucuronate (GlcA) residues present in chondroitin sulfate are re placed by their epimer, iduronate (IdoA).

Keratan sulfates (Greek keras, “horn”) have no uronic acid and their sulfate content is variable. They are present in cornea, cartilage, bone, and a variety of horny structures formed of dead cells: horn, hair, hoofs, nails, and claws. Heparin (Greek he–par, “liver”) is a natural anticoagulant made in mast cells (a type of leukocyte) and released into the blood, where it inhibits blood coagulation by binding to the protein antithrombin. He parin binding causes antithrombin to bind to and inhibit thrombin, a protease essential to blood clotting. The in teraction is strongly electrostatic; heparin has the highest negative charge density of any known biological macromolecule (Fig. 7–25). Purified heparin is routinely added to blood samples obtained for clinical analysis, and to blood donated for transfusion, to prevent clotting. Table 7–2 summarizes the composition, properties, roles, and occurrence of the polysaccharides described in Section 7.2.

FIGURE 7–24 Repeating units of some common glycosaminoglycans of extracellular matrix. The molecules are copolymers of alternating uronic acid and amino sugar residues, with sulfate esters in any of several positions. The ionized carboxylate and sulfate groups (red) give these polymers their characteristic high negative charge. Heparin contains primarily iduronic acid (IdoA) and a smaller proportion of glucuronic acid (GlcA), and is generally highly sulfated and heterogeneous in length. Heparan sulfate (not shown) is similar to heparin but has a higher proportion of GlcA and fewer sulfate groups, arranged in a less regular pattern.

FIGURE 7–25 Interaction between a glycosaminoglycan and its binding protein. Fibroblast growth factor (FGF1), its cell surface receptor (FGFR), and a short segment of a glycosaminoglycan (heparin) were co-crystallized to yield the structure shown here (PDB ID 1E0O). The proteins are represented as surface contour images, with color to rep resent surface electrostatic potential: red, predominantly negative charge; blue, predominantly positive charge. Heparin is shown in a ball-and-stick representation, with the negative charges (-SO^-₃ and -CO^-) attracted to the positive (blue) surface of the FGF protein. Heparin was used in this experiment, but, in vivo, the glycosamino glycan that binds FGF is heparan sulfate on the cell surface.

اخر الاخبار

اخبار العتبة العباسية المقدسة

مشاتل الكفيل توفر 8 آلاف شتلة نباتية متنوّعة لدعم السوق المحلي

المجمع العلمي يُقيم جلسةً عن فنّ الأداء القرآني للقرّاء في الديوانية

قسم شؤون المعارف يناقش مشاريع مركز تراث الجنوب ويستعرض نسب إنجازها

قسم الشؤون الخدمية يجري حملة غسل لمحيط العتبة العباسية المقدسة وتنظيفه

المزيد

الآخبار الصحية

أطعمة مفيدة وأخرى ضارة للأسنان

دراسة تكشف تأثيرا خفيا لتناول المانجو والأفوكادو معاً

لكسر الإدمان وحماية الصحة.. بدائل طبيعية للسكر المعالج

قرار تاريخي في بريطانيا.. منع التدخين تماما لمواليد 2008

المزيد

الآخبار التكنلوجية

10 أخطاء يومية تدمّر سيارتك ومحركها بصمت: كيف تحافظ عليها؟

روسيا.. تطوير هيدروجيل حيوي لتحسين كفاءة الري وتنظيم رطوبة التربة

حل لغز البرق البركاني ؟

تطبيق ذكاء اصطناعي يتصفح الإنترنت ومنصات التواصل بدلا عنك !

المزيد

مواضيع ذات صلة

Polysaccharides:- Bacterial and Algal Cell Walls Contain Structural Hetero polysaccharides

Polysaccharides: -Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding

Polysaccharides:- Some Homopolysaccharides Serve Structural Roles

Polysaccharides:- Some Homopolysaccharides Are Stored Forms of Fuel

Monosaccharides and Disaccharides:- Disaccharides Contain a Glycosidic Bond

Monosaccharides and Disaccharides:- Monosaccharides Are Reducing Agents

Monosaccharides and Disaccharides:- Organisms Contain a Variety of Hexose Derivatives

Monosaccharides and Disaccharides:- The Common Monosaccharides Have Cyclic Structures

Monosaccharides and Disaccharides:- Monosaccharides Have Asymmetric Centers

Monosaccharides and Disaccharides: - The Two Families of Monosaccharides Are Aldoses and Ketoses

Regulatory Enzymes:- Some Enzymes and Other Proteins Are Regulated by Proteolytic Cleavage of an Enzyme Precursor

Regulatory Enzymes:- Multiple Phosphorylations Allow Exquisite Regulatory Control