Dr. Saidunnisa Professor of Biochemistry Carbohydrates-II

Learning Objectives At the end of the session student shall be able to: Define Polysaccharides List homopolysaccharides and explains the biomedical importance of each. List biologically important sugar derivatives with its clinical importance. Define and lists various Glycosaminoglycans and explains the biomedical importance of each and correlate to lysosomal storage disorders.

Polysaccharides They contain more than ten monosaccharide units. These are of two types; 1. Homo polysaccharides. 2. Hetero polysaccharides. ( GAGS)

Homo polysaccharides. Made up of same single monosaccharide units. Examples: 1. Starch 2. Cellulose 3. Glycogen 4. Inulin 5. Dextrans 6. Chitin

Starch Carbohydrate reserve of the plants. Important dietary source of man. High content is present in cereals, roots, tubers. It is made up of multiple units of alpha-D Glucose.

Structure of Starch and its components Amylose water soluble, unbranched, gives blue colour with iodine Amylopectin Water insoluble, branched, gives violet colour with iodine

Degradation Starches are hydrolyzed by amylase to liberate dextrin's. Dextrin's are finally converted to Maltose and glucose

Cellulose Exclusively present in plant kingdom. Totally absent in animal body. Made up of beta-D glucose units linked by beta glycosidic linkages. Cannot be digested in humans. Major constituent of dietary fiber.

Learning Check? Cellulose though not digested, has great importance in human nutrition why?

1. Improves glucose tolerance 2. Decresaes blood cholesterol 3. Relives constipation by increasing the bulk of the feces.

Glycogen Animal reserve of the body. Present in high concentration in liver, muscle and brain. Similar to Amylopectin, made up of repeated units of alpha-D-Glucose linked by glycosidic linkages.

Structure of Glycogen

Inulin Polymer of fructose. Present in garlic, onion, dahlia bulbs etc. Low molecular weight easily soluble in water. Not utilized by the body. Used for assessing kidney function through GFR.

Dextrans High molecular weight. Polymer of Alpha-D glucose linked by glycosidic linkages. Used as an plasma expander. When given I.V in cases of blood loss (Hemorrhage), it increase the blood volume.

Learning check Dextrose, Dextrin, and Dextran are same or different molecules?

Chitin Composed of N-acetyl-D-glucosamine. Found in exoskeleton of some invertebrates.

Hetero polysaccharides Glycosaminoglycans (GAGs) important constituents of ECM (extra cellular matrix).

Extra cellular matrix (ECM) The ECM is often referred to as the connective tissue made up of: Ground substances Cartilages, Tendons, ligaments, Vascular wall, Skin, Lung Cornea

Functions Mechanical support Lubrication Cushioning

Extracellular matrix (ECM) The ECM is composed of 3 major classes of biomolecules: 1. Structural proteins: collagen and elastin. 2. Specialized proteins: e.g. fibrillin, fibronectin, and laminin. 3. Proteoglycans: GAGS

Synthesis and Degradation These are synthesized in ER and modifications like sulfation takes place in Golgi complex. These are degraded by lysosomal enzymes. Inability to degrade leads to a set of disease known as Lysosomal storage disease or mucopolysaccharidoses.

Classification 1. Hyaluronic acid 2. Chondroitin sulfate 3. Heparin 4. Dermatan sulfate. 5. Keratan sulfate All gags are covalently attached to protein forming proteoglycan.

Resilience of GAGS Resilience of GAGS There are negatively charged COO - and SO 4 – groups on the GAG which bind to positively charged hydrogen ions of water molecules thereby creating a hydrated gel. Negative charge imparts high viscosity and low compressibility which makes them ideal for lubricating fluid in the joints.

Constituents of GAGS are repeating sugar derivatives These units contain a 1. Amino sugar: (N acetyl glucosamine / galactosamine) & 2.Uronic acid: (Glucuronic / iduronic acid).

1. Hyaluronic Acid Disaccharide unit-N- acetyl glucosamine & Glucuronic acid. Found in Synovial fluid; vitreous humor of eyes connective tissue, and forms gel around ovum. Only GAG not sulfated. Serves as a lubricant and shock absorbent in joints.

Learning Check What is Hyaluronidase? (hint: fertilization)

2. Chondroitin 4-and 6 sulfate Most abundant GAG in the body. Found in cartilage (Chondros); tendons ligaments; and aorta. Disaccharide unit-N-acetyl galactosamine (with sulfate on either C-4;C- 6)and Glucuronic acid. Loss of Chondroitin sulfate from the cartilage causes osteoarthritis.

3. Heparin Disaccharide unit (glucosamine sulfated at C2;C6 & Glucuronic sulfated at C2). Found as an intracellular component of mast cells that line arteries of liver; lung & skin. Acts as an anticoagulant.

Case A 76-year old woman who is bed bound in a nursing home begins to develop swelling of her left leg. She is evaluated for deep vein thrombosis; she is immediately started on heparin to further prevent the clot. What is Heparin and its components ? What is its action?

4. Dermatan sulfate Disaccharide unit (N- acetyl galactosamine and L- iduronic acid). Found in skin; blood vessels and heart valves.

Learning check What is the difference between Dermatan sulfate and Chondroitin sulfate?

5. Keratan sulfate Disaccharide unit (N acetyl glucosamine& galactose; sulfate may be present on C6 of either sugar) does not contain uronic acid. Found in cornea responsible for transparency of cornea.

Summary GAGRepeating DisaccharideTissue distribution Hyaluronic Acid N-acetyl glucosamine (Not sulfated) Glucuronic acid. Synovial fluid Chondroitin 4-and 6 sulfate N-acetyl galactosamine(sulf ated) Glucuronic acid Cartilages Heparinglucosamine (sulfated ) Glucuronic sulfated line arteries Dermatan sulfate N-acetyl galactosamine L- iduronic acid Skin Keratan sulfate N acetyl glucosamine& galactose; sulfate does not contain uronic acid cornea

Pathogenesis of hypothyroidism The characteristic finding is the accumulation of glycosaminoglycans (mostly hyaluronic acid) in interstitial tissue. This results in interstitial edema (e.g. in skin, heart muscle etc.). The accumulation is due to decreased destruction of glycosaminoglycans.

Pathogenesis of hypothyroidism The characteristic finding is the accumulation of glycosaminoglycans (mostly hyaluronic acid) in interstitial tissue. This results in interstitial edema (e.g. in skin, heart muscle etc.). The accumulation is due to decreased destruction of glycosaminoglycans.

Structure of Proteoglycans The Proteoglycans are essential parts of extracellular matrix, The majority of GAGs in the body are linked to core proteins, forming Proteoglycans. The linkage of GAGs to the protein core involves a specific trisaccharide composed of two Galactose residues and a xylose residue (GAG-GalGalXyl-O- CH 2 -protein). This is linked to the protein core through an O- glycosidic bond.

Proteoglycan structure The GAGs extend perpendicularly from the core in a brush- like structure.

Lysosomal storage disorders or MPS

Diagnosis Wide spread deposits in tissues of a particular GAGS. Excessive excretion of GAG in Urine. Detection of GAG in urine: Cetyl trimethyl ammonium bromide test.