Carbohydrate II PDF - Biochemistry 1

Biochemistry 1 Carbohydrate II CARBOHYDRATE-II Intended Learning Outcomes (ILOs): This lecture will enable the students to: ▪ Describe the glycosidic linkage. ▪ Define oligosaccharides and polysaccharides. ▪ Understa...

Biochemistry 1 Carbohydrate II CARBOHYDRATE-II Intended Learning Outcomes (ILOs): This lecture will enable the students to: ▪ Describe the glycosidic linkage. ▪ Define oligosaccharides and polysaccharides. ▪ Understand nomenclature, structure & properties of disaccharides & polysaccharides. ▪ Classify disaccharides and polysaccharides ▪ List important disaccharides (e.g., maltose, lactose and sucrose). ▪ Distinguish between polysaccharides and their derivatives; glycosaminoglycans, proteoglycans and glycoproteins By: Dr. Tamer A. Al-Shafie Assoc. Professor of Medical Biochemistry Dr. Tamer A. Al-Shafie -1- Biochemistry 1 Carbohydrate II Glycosidic Linkage: Monosaccharides are joined by glycosidic bonds to form oligosaccharides and polysaccharides. Glycosidic bonds are formed by enzymes known as: glycosyltransferases and hydrolyzed to produce 2 monosaccharide molecules by enzymes known as: glycosidases. Glycosidic bonds between sugars are named according to the carbon atoms involved in the bond. For example, Lactose is synthesized by forming a glycosidic bond between C 1 of β- galactose and C 4 of glucose. The linkage is, therefore, a β (1→ 4) glycosidic bond. Thus, Lactose = galactosyl- β (1, 4)-glucose Monosaccharides can also be attached by glycosidic bonds to non-carbohydrates. This includes binding with: – Purine and pyrimidine bases in nucleic acids – Aromatic rings as in steroids and bilirubin – proteins as in glycoproteins and proteoglycans – lipids as in glycolipids N- and O-glycosides: If the sugar is attached to an –NH2 group, the structure is an N-glycoside and the bond is called an N-glycosidic link. If the sugar is attached to an –OH (as in sugar-sugar bond), the structure is an O- glycoside, and the bond is an O-glycosidic link. Dr. Tamer A. Al-Shafie -2- Biochemistry 1 Carbohydrate II B. Oligosaccharides Oligosaccharides are molecules that are formed from few (3-10 units) different monosaccharide units including: hexoses (e.g., glucose, fructose, mannose, and galactose) and pentoses (e.g., ribose and xylose). Disaccharides: The simplest oligosaccharides are the disaccharides, which consist of two monosaccharide units linked by a glycosidic bond. Each unit in an oligosaccharide is termed: residue or moiety. Classification: Disaccharides can be classified into: # Homo-disaccharide: formed of 2 similar monosaccharide units, e.g., maltose, isomaltose, cellobiose & trehalose (all consist of 2 glucose units but vary in bond type) # Hetero-disaccharides: formed of 2 different monosaccharide units, including: sucrose (glucose + fructose), lactose (galactose + glucose) A. Nomenclature & Reducing Characteristics Remember!! The Anomeric carbon is present in the ring form of the sugar and represents the sugar carbonyl carbon responsible for its reducing properties. In many disaccharides (e.g., Lactose and Maltose), the anomeric carbon of one unit monosaccharide is involved in the glycosidic linkage while the other is free. So, lactose and maltose are reducing sugars, as one of the two units may have an open-chain form with an aldehyde group. In some disaccharides, anomeric carbon of both monosaccharide units are involved in the glycosidic linkage (e.g., Sucrose). So, sucrose is a non-reducing sugar because neither of the two rings is capable of opening. 1. Lactose (Milk sugar) Chemistry: β-D-galactose and α-D-glucose linked by β-1, 4-galactosidic linkage. The glucose residue has a free anomeric carbon atom, hence: It exists in α- and β- forms. − It is a reducing sugar Sources: It is only found in milk. Hydrolysis: it can be hydrolysed into D- galactose and D-glucose by acid or lactase enzyme in the intestine. Dr. Tamer A. Al-Shafie -3- Biochemistry 1 Carbohydrate II 2. Maltose (Malt sugar) Chemistry: it contains two D-glucose residues linked by α-1-4 glucosidic bond. The second glucose residue has a free anomeric carbon atom, hence: − It exists in α- and β- forms. − It is a reducing sugar Sources: − Germinating cereals and malt. − The intermediate product of the action of amylases on starch. Hydrolysis: it can be hydrolyzed into two D-glucose units by acid or maltase enzyme. Free anomeric carbon (reducing end) 3. Sucrose: (Cane sugar = Table sugar = Beet sugar) Chemistry: It contains β-D-fructose & α-D-glucose linked by (α-1, 2)-glucosidic linkage. The anomeric carbon atoms of the two hexoses are linked to each other, thus, sucrose contains no free anomeric carbon atom so: – It does not occur in α- or β-forms. – It is a non-reducing sugar. Sources: Sugar cane and sugar beet. Hydrolysis: it can be hydrolyzed into D-glucose and D-fructose by acids or sucrase (invertase enzyme). No Free anomeric carbon no (reducing end) Dr. Tamer A. Al-Shafie -4- Biochemistry 1 Carbohydrate II C. Polysaccharides (Glycans) "Polysaccharides (Poly- Many): >10 units" Polysaccharides are sugars that contain tens to thousands of monosaccharide units joined by glycosidic bonds to form linear chains or branched structures. Polysaccharides differ according to: 1. Chain length and branching 2. Type of the constituting monosaccharide units. 1. Polysaccharide chains: Polysaccharides chain lengths vary from tens to thousands of monosaccharide units. Branches in polysaccharides involve (— OH) groups on the monosaccharide components. ←Linear Chain Branched Chain↓ 2. Type of the constituting monosaccharide units The most common monosaccharide constituent of polysaccharides is D-glucose, but D- fructose, D-galactose, L-galactose, D-mannose, L-arabinose, and D-xylose are also common. Polysaccharide Functions: − Storage polysaccharides (e.g., Starch and glycogen), as readily metabolizable food, provide energy reserves for cells. − Tissue structural polysaccharides (e.g., Chitin and cellulose) provide strong support for the skeletons of arthropods and green plants, respectively. − Cell membrane structural polysaccharides (e.g., Mucopolysaccharides, such as hyaluronic acids), form protective coats on animal cells and are involved in cellular recognition & cellular communication events. Dr. Tamer A. Al-Shafie -5- Biochemistry 1 Carbohydrate II According to type of monosaccharide units, polysaccharides can be classified into: Homopolysaccharides & Heteropolysaccharides 1. HOMOPOLYSACCHARIDES These are polysaccharides that contain only one type of monosaccharide molecule. They contribute to two major functions: Storage polysaccharides (e.g., Starch and Glycogen) Structural Polysaccharides (e.g., Cellulose and Chitin) ▪ Starch Starch is a glucose homopolymer of plant origin. It is the major storage polysaccharide in our food and the most important dietary carbohydrate in cereals, potatoes, and legumes The glucose forming units are attached by α-glucosidic chain. Starch includes two types: amylose and amylopectin: – Amylose (MW 10,000-50,000 KD) consists of long, unbranched chains of glucose residues connected by (α1→4) linkages. – Amylopectin (MW 50,000-1,000,000 KD), unlike amylose, amylopectin is branched. The glycosidic linkages join successive glucose residues in amylopectin chains via (α1→4) linkages; the branch points occur every 24 - 30 residues via (α1→6) linkages. Dr. Tamer A. Al-Shafie -6-  Biochemistry 1 Carbohydrate II ▪ Glycogen Glycogen is the main storage polysaccharide in the human body. Glycogen is a homopolymer of (α1→4)-linked subunits of glucose, with (α1→6)-linked branches. Glycogen is more extensively branched (on average, every 8 to 12 residues) than amylopectin. Glycogen is especially abundant in the liver and skeletal muscle. 2. HETEROPOLYSACCHARIDES = Glycosaminoglycans (GAGs) General properties: GAGs have a common structural feature: They consist of linear chains of repeating disaccharides units either: hexose (e.g. galactose), hexosamine (e.g. galactosamine, glucosamine) or hexuronic acid (e.g. glucuronic acid and iduronic acid). − They are also called: Mucopolysaccharides (MPS). − They Contain a mixture of monosaccharides and their derivatives. − Polar and gelatinous with high MW (up to 5×106 KD). − Present mainly in the connective tissues extra-cellular matrix (ECM). − Negatively-charged due to the presence of a sulfate residue, except hyaluronic acid. Types of Glycosaminoglycans (GAGs) Dr. Tamer A. Al-Shafie -7- Biochemistry 1 Carbohydrate II Function of Glycosaminoglycans (GAGs): ▪ Hyaluronic acid HA ✓ Disaccharide unit: N-acetylglucosamine and glucuronic acid. ✓ Different from other GAGs: Unsulfated, not covalently attached to the protein, and the only GAG not limited to animal tissue, but also found in bacteria. ✓ Occurrence: synovial fluid of joints, the vitreous humor of the eye, the umbilical cord, connective tissue and cartilage serving as a lubricant and shock absorber. ✓ The medical importance of Hyaluronic Acid (HA) 1. Age-related disturbances: − Age-related pains: As age advances hyaluronic acid is replaced by dermatan sulfate in synovial fluid which is not a good lubricant; whivh leads to joint pain. − Age-related vision affections: Vitreous is a clear elastic gel in which hyaluronic acid is associated with collagen. As age advances vitreous elasticity is reduced due to decreased association between collagen and hyaluronic acid. − Age-related scar formation HA content of skin decreases as age advances facilitating the formation of scars of the skin. 2. Hyaluronic acid is involved in wound healing. In the initial phase of wound healing, hyaluronic acid concentration increases many fold at the wound site to allow rapid migration of the cells to the site of connective tissue development. 3. It has a role in the migration and metastasis of tumor cells. 4. Some pathogenic bacteria (e.g. pneumonia and meningitis) contain hyaluronate lyase which facilitates invasion of a host by these bacteria through hydrolysis of HA by this enzyme. ▪ Chondroitin Sulfates CS ✓ Disaccharide unit: N-acetylgalactosamine with sulfate on either C4 or C6, and glucuronic acid. ✓ Occurrence: Most abundant GAGs in the body; found in cartilage, tendons, ligaments, and aorta. Dr. Tamer A. Al-Shafie -8-  Biochemistry 1 Carbohydrate II Chondroitin-4-sulfate Chondroitin-6-sulfate ▪ Dermatan Sulfate DS ✓ Disaccharide unit: N-acetylgalactosamine and L-iduronic acid ✓ Occurence: skin, blood vessels, and heart valves. ▪ Heparin/Heparan sulfate ✓ Disaccharide unit: Glucosamine and glucuronic or iduronic acid. ✓ Glucosamine residues are mostly bound in sulfamide linkages. ✓ Sulfate is also found on C-3 or C-6 of glucosamine and C-2 of uronic acid. ✓ Occurrence: heparin is an intracellular component of mast cells that line arteries, especially in the liver, lungs, and skin. ✓ Used as an anticoagulant. It binds to antithrombin III (a protein involved in the termination of the clotting process). Dr. Tamer A. Al-Shafie -9-  Biochemistry 1 Carbohydrate II ▪ Keratan Sulfate KS ✓ Disaccharide unit: N-acetylglucosamine and galactose (KS DOESN'T contain uronic a.) ✓ Sulfate content is variable and may be present on C-6 of either sugar. ✓ Most heterogeneous GAGs because they contain monosaccharides such as L-fucose, N-acetyl-neuraminic acid, and mannose. ✓ Occurrence: Cornea, Cartilage, Bone, horny structures Summary of Glycosaminoglycans (GAGs) Dr. Tamer A. Al-Shafie -10- Biochemistry 1 Carbohydrate II Derived Polysaccharides ▪ Proteoglycans Except for hyaluronic acid, ALL glycosaminoglycans are covalently attached to a core protein forming Proteoglycans They represent a subclass of Glycoproteins. ▪ Proteoglycan = Glycosaminoglycans (GAGs) + protein Structure of Proteoglycans The linkage between GAG chain and core protein is most commonly through a trihexoside (gala-gala-xyl) and a serine residue respectively. A glycosidic bond is formed between the xylose and the hydroxyl group of the serine. The function of proteoglycans: 1. Many proteoglycans are components of the connective tissue (extra-cellular matrix (ECM) (e.g., Aggrecan). 2. Some are integral membrane proteins (e.g., Syndecan). ▪ Glycoproteins Glycoproteins are found in mucous fluids, tissues, blood, and cell membrane. They are proteins containing short chains of carbohydrates, usually oligosaccharides. These oligosaccharide chains are attached to proteins by O-glycosidic and N-glycosidic bonds. ▪ Glycoprotein = Carbohydrate + Protein The oligosaccharide chains of glycoproteins have important functions: 1. They present on the surface of erythrocytes and determine blood groups; they are responsible for the classification of blood groups. 2. Cell-cell communication depends on oligosaccharide chains of glycoproteins. Dr. Tamer A. Al-Shafie -11- Biochemistry 1 Carbohydrate II Extracellular matrix (ECM) It is a component of the connective tissue that holds the cells together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells. The ECM is composed of two major classes of biomolecules: ✓ Proteoglycans: Glycosaminoglycans (GAGs) are covalently linked to protein. ✓ Fibrous proteins: include collagen, elastin, fibronectin, and laminin. …End of Lecture… Thank You Dr. Tamer A. Al-Shafie -12-