Carbohydrates are aldehyde or ketone compounds with multiple hydroxyl groups Have multiple roles in all forms of life

Transcription

1 Carbohydrates 1

2 Carbohydrates are aldehyde or ketone compounds with multiple hydroxyl groups Have multiple roles in all forms of life Classification Serve as energy stores, fuels, and metabolic intermediates Ribose and deoxyribose sugars form part of the structural network of RNA and DNA Structural elements in the cell walls of bacteria and plants Carbohydrates are linked to many proteins (eg mannose) and lipids (eg galactose) Recent evidence suggests that carbohydrates units on the cell surface play key roles in the cell-cell recognition 1. Monosaccharides Simple sugars Can not be hydrolyzed into a simpler form May be classified as aldoses or ketoses depending upon whether the aldehyde or ketone group is present 2. Disaccharides Yield two molecules of the same or of different monosaccharides Eg Sucrose, lactose, and maltose 2

3 3. Oligosaccharides Yield 3-6 monosaccharide units on hydrolysis Oligosaccharides in most cells do not occur as free entities but are joined to nonsugar molecules (lipids and proteins) to form glycoconjugates Monosaccharides,disaccharides and oligosaccharides are water soluble because of high hydrogen binding potential 4. Polysaccharides yield more than 6 molecules of monosaccharide on hydrolysis May be linear or branched Many polysaccharides are insoluble because their large size increases the opportunity for intermolecular interactions. Molecules tend to interact more strongly with each other than with water 3

4 Monosaccharides Aldoses Three carbon aldoses: Glyceraldehyde Four carbon aldoses: D-Erythrose, D-Threose Five carbon aldoses: D-Ribose, D- Arabinose, D-Xylose, D-Lyxose Six Carbon aldoses: D- Glucose, D-Mannose, D-Galactose etc Ketoses Three carbon ketoses: Dihydroxyacetone Four carbon aldoses: D-Erythrulose Five carbon aldoses: D-Ribulose, D-Xylulose Six Carbon aldoses: D- Fructose etc Most of the monosaccharides occurring in mammalian metabolism are of the D- configuration D- Fructose is the most abundant ketose Pentoses and hexoses cyclize to form furanose (5-membered )and pyranose (6- membered) rings 4

5 Hexoses of physiological importance Sugar D-glucose Importance Sugar carried in the blood and the principal one used by the tissues D-fructose D-galactose D-mannose Can be changed to glucose in the liver and intestine and used in the body Can be changed to glucose in the liver. Synthesized in the mammary gland to make lactose in milk A constituent of prosthetic polysaccharides of albumins, globulins, mucoproteins. Occurs in glycoproteins 5

6 Carbohydrates are joined to alcohols and amines by O- and N- glycosidic bonds respectively Hexose derivatives In addition to simple hexoses such as glucose, galactose and mannose there are a number of sugar derivatives.eg glucosamine, N-Acetyl glucosamine, etc 6

7 DISACCHARIDES Disaccharides (such as maltose, lactose, and sucrose) consist of two monosaccharides joined covalently by an O-glycosidic bond Maltose Two D-glucose monosaccharides are linked through O-glycosidic bonds Hydrolyzed by maltase Lactose D-galactose is linked to D-glucose through O-glycosidic bonds Lactose is hydrolyzed by lactase In lactase deficiency, malabsorption leads to diarrhoea and flatulence Lactose accumulates in the lumen of the small intestine because there is no mechanism for the uptake of the disaccharide Osmotic effects of unabsorbed lactose leads to influx of fluid into the small intestine 7

8 Sucrose Table sugar D-glucose monosaccharide and a D-fructose monosaccharide are joined in this disaccharide Hydrolyzed by sucrase. Deficiency of this enzyme may lead to diarrhoea and flatulence 8

9 POLYSACCHARIDES Most carbohydrates in nature occur as polysaccharides (glycans), polymers of medium to high molecular weight Homopolysaccharides contain only a single type of monomer Some serve as storage forms of monosaccharides and are used for fuel eg starch and glycogen Others serve as structural elements in plant cell walls and animal exoskeletons eg cellulose and chitin Heteropolysaccharides contain two or more different types of monomers Provide extracellular support for all organisms Glycogen The main storage polysaccharide in animal cells It s a very large branched polymer of glucose A polymer of (α1 4)-linked subunits of glucose The branches are formed by the α1 6 glycosidic bonds. Branches occur about once in ten glucose units This branching increases the solubility of glycogen and makes its sugar units accessible Abundant in the liver (10% of liver mass). Also present in skeletal muscles (2% of muscle mass). 9

10 Degradative enzymes that act only at the nonreducing ends can work simultaneously on the many branches speeding up the process Glucose can not be stored in its monomeric form because The concentration of glucose in the cells that would be equivalent to stored glycogen is too high, and this can lead to osmotic destruction of the cells The free-energy change for entry of glucose into the cells against the concentration gradient would be prohibitively large 10

11 Starch The nutritional reservoir in plants Two types Amylose (10-30%) -Unbranched -Glucose residues linked by α1 4 bonds -Reacts with iodine to give a dark blue complex Amylopectin (70-90%) -The branched form -Has about one α1 6 linkage per 30 α1 4 linkages (like glycogen except for the lower degree of branching) -Gives a red-violet colour with iodine Both amylose and amylopectin are hydrolyzed by α amylase (found in human saliva) α amylase hydrolyzes internal α1 4 linkages to yield maltose (2 glucose residues in α1 4 linkage), maltotriose (3 glucose residues in α1 4 linkages), and α-dextrin (several glucose units joined by an α1 6 linkage in addition to α1 4 linkages) Maltose and maltotrioses are hydrolyzed to glucose by maltase α-dextrin is hydrolyzed to glucose by α-dextrinase 11

12 Dextran Storage polysaccharide in yeasts and bacteria Consists only of glucose residues Nearly all linkages are α1 6 Dextrans formed by bacteria are components of dental plaque Bacteria cell walls contain peptidoglycans Definition: Peptidoglycans are linear polysaccharide chains that are cross-linked by short peptides The rigid component of the bacteria cell walls is a heteropolymer of alternating β1 4 linked N-acetylglucosamine and N-acetyl muramic acid residues The linear polymers lie side by side in the cell wall cross-linked by short peptides Gram positive bacteria like staphylococcal aureus have a pentaglycine chain in the cross link The cross-links hold the polysaccharide chains into a strong sheath that envelopes the entire cell and prevents cellular swelling and lysis due to osmotic entry of water The enzyme lysozyme kills bacteria by hydrolyzing the β1 4 linkages Penicillin and other related antibiotics kill bacteria by preventing synthesis of cross links leaving the cell wall too weak to resist osmotic lysis 12

13 Glycosaminoglycans are anionic polysaccharide chains made of repeating disaccharide units The extracellular space in the tissues of multicellular animals is filled with a gellike extracellular matrix The extracellular matrix is composed of an interlocking meshwork of heteropolysaccharides (Glycosaminoglycans) and fibrous proteins such as collagen, elastin, fibronectin etc Glycosaminoglycans are linear polymers composed of repeating disaccharide units and have a very high density of negative charge To minimize repulsive forces among neighbouring groups these molecules assume an extended conformation in solution When brought together they slip past each other like like-poles of a magnet Squeezing water out of glycosaminoglycans decreases their volume On releasing the compression they return back to their original hydrated state Glycosaminoglycans are attached to extracellular proteins to form proteoglycans 13

14 Importance of glycosaminoglycans They have the ability to bind large amounts of water to form gel like matrix that forms the basis for the body s ground substance They stabilize and support cellular and fibrous components Help maintain water and salt balance Play a role in mediating cell to cell interactions Synovial fluid glycosaminoglycans serve as lubricants in joints, tendon sheaths.. 14

15 GLYCOCONJUGATES: PROTEOGLYCANS, GLYCOPROTEINS AND GLYCOLIPIDS There are two types of sugar containing proteins Proteoglycans have long, linear unbranched heteropolysaccharide with a disaccharide repeating unit Glycoproteins have short oligosaccharides, which are highly branched and do not contain disaccharide repeating units Proteoglycans (Mucopolysaccharides) Proteoglycans are macromolecules on the cell surface or extracellular matrix in which one or more glycosaminoglycans are joined covalently to a membrane protein or secreted protein Proteoglycans are major components of connective tissue such as cartilage in which interactions with other proteoglycans, proteins and glycosaminoglycans provide strength and resilience 15

16 Glycoproteins are information rich conjugates containing oligosaccharides Are carbohydrate-protein conjugates The carbohydrate is attached to protein through one of its carbon atoms. Many of the proteins secreted by eukaryotic cells are glycoproteins eg antibodies and some hormones like luteinizing hormone, follicle stimulating hormone etc Some glycoproteins have a single oligosaccharide chain but many have more than one Functions of the oligosaccharides Stabilize the proteins against denaturation Protect the proteins from proteolytic cleavage Enhance the solubility of proteins Serve as recognition signals for transport and cell-cell interactions Viscous properties of mucins derive from the high content of negatively charged sialic acid residues In mucins the oligosaccharides are usually short branched structures containing sialic acid in addition to other hexose derivatives When sialic acid residues are present in clusters they repel each other and prevent protein folding The result is the protein assumes an extended state, yielding viscous (mucous) solutions 16

17 Glycolipids and lipopolysaccharides are membrane components Glycolipids Some lipids have covalently bound oligosaccharides Oligosaccharide moieties are generally found on the outer face of the plasma membrane Gangliosides are membrane lipids of eukaryotic cells with a complex oligosaccharide containing sialic acid and other monosaccharide residues Lipopolysaccharides are the dominant surface feature of the outer membrane of gram-negative bacteria Important targets of the antibodies produced in response to bacterial infection Important determinants of bacterial strain Lipopolysaccharides produced by some bacteria are toxic to humans low BP toxic shock syndrome Oligosaccharide-lectin interactions mediate many biological processes Lectins are found in all organisms, They are proteins that bind carbohydrates with high affinity and specificity Serve in a variety of cell-cell recognition and adhesion processes Pathogens Bacteria E.Coli has lectins that recognize oligosaccharide units of the surface of the target cells of the gastro intestinal tract Neisseria gonococci infects human genital and oral epithelia cells but not those of other species because their surfaces lack carbohydrates that are recognized by the pathogen Influenza virus contains a hemagglutinin protein that recognizes sialic acid residues on cells lining the respiratory tract 17

18 Study questions 1.What are monosaccharides? 2.What are disaccharides? 3.When lactose is hydrolyzed which simple sugars are formed? 4.When sucrose is hydrolyzed which simple sugars are formed? 5.What is the function of lactase? 6.What is the main storage polysaccharide in animal cells? 7.Why are many polysaccharides insoluble? 8.What is the most abundant ketose? 9.Why is branching important in glycogen? 10.What is the storage polysaccharide in yeasts and bacteria? 11.How does penicillin and other related antibiotics kill bacteria? 12.Where are lipopolysaccharides found? 13.What is the importance of lipopolysaccharides? 14.What are glycoproteins? 15.Explain why mucins have viscous properties. 18