PHTH1011 009 Carbohydrate Metabolism 1&2 - Bryan.pdf

PHTH1011: CARBOHYDRATE STRUCTURE (LECTURES 1 & 2) 1 DR. S. BRYAN MACROMOLECULES Large, carbon-based organic molecules. Created by polymerization of smaller subunits. Four major types: 1. Carbohydrates – monosaccharides 2. Proteins – amino acids 3. Nucleic acids – nucleotides 4. Lipids- no true basic...

PHTH1011: CARBOHYDRATE STRUCTURE (LECTURES 1 & 2) 1 DR. S. BRYAN MACROMOLECULES Large, carbon-based organic molecules. Created by polymerization of smaller subunits. Four major types: 1. Carbohydrates – monosaccharides 2. Proteins – amino acids 3. Nucleic acids – nucleotides 4. Lipids- no true basic units = fatty acids + glycerol Body can obtain energy from carbohydrates, lipids and proteins but carbohydrates are used first, if available. 2 CARBOHYDRATES Primary source of energy Structural components (cell membrane) Part of backbone of nucleic acids (DNA and RNA) Role in cell identification, signaling 3 CARBOHYDRATES Carbohydrates are carbon-based molecules rich in hydroxyl groups and thus are known as polyhydroxy aldehydes and ketones. Most abundant carbohydrate is glucose, C6H12O6 and is the most important simple carbohydrate in human metabolism. 4 CLASS QUESTION General empirical formula is Cn(H2O)n. Question: If a carbohydrate has 5 carbons, what would be its molecular formula? 5 CLASSIFICATION OF MONOSACCHARIDES Monosaccharides are classified based on either number of carbon atoms or characteristic carbonyl group. According to the number of carbon atoms: Trioses, tetroses, pentoses, hexoses, heptoses, octoses. According to the characteristic carbonyl group: Aldehyde group or ketone group. 6 Classification of Carbohydrates Simple Carbohydrates Monosaccharides (single sugar unit) Disaccharides (2 sugar units) Complex Carbohydrates Oligosaccharides (3 to 10 sugar units) Polysaccharides (10 or more sugar units) 7 CLASSIFICATION OF CARBOHYDRATES Homopolysaccharides- consist of the same monosaccharides (eg. starch, cellulose) Heteropolysaccharides- different monosaccharides (eg. hyaluronic acid) 8 MONOSACCHARIDES Aldo sugars: Aldoses Monosaccharides containing aldehyde group eg. glucose, ribose. Keto sugars: Ketoses Monosaccharides containing ketone group eg. fructose, ribulose. 9 Classification of Carbohydrates An aldose has the carbonyl on C1 (aldehyde). A ketose has the carbonyl on C2 (ketone). Since a 4-Carbon sugar is a tetrose, then an aldotetrose is a 4-Carbon sugar that contains an aldehyde functional group. 10 Identify the aldose or ketose below: Straight chain structures 10 11 Monosaccharide Structures Straight chain structures glyceraldehyde ribose glucose fructose 12 MONOSACCHARIDES The most common monosaccharides have 3-8 carbon atoms. The suffix –ose indicates that a molecule is a ‘sugar’- carbohydrate. The prefixes tri-, tetr-, pent- etc indicate the number of carbon atoms in the monosaccharide. 13 MONOSACCHARIDES Simpliest monosaccharides are two 3- Carbon trioses: Glyceraldehyde (an aldotriose) Dihydroxyacetone (a ketotriose) Except for glyceraldehyde and fructose, most of the carbohydrates of interest in human biochemistry are aldohexoses or aldopentoses. 14 MONOSACCHARIDES: STRUCTURE 15 MONOSACCHARIDES STRUCTURE Cannot be hydrolyzed to any simpler form. Monosaccharides exist as: Linear form (Fischer’s projection) Cyclic form (Haworth’s formation) Chair conformations (naturally, as a threedimensional boat form). The linear form of monosaccharides is not very stable, hence pentoses and hexoses tend to form rings to improve stability. 16 17 Classifications of IsomerismCarbohydrates Aldose-ketose isomerism D- and L- forms Enantiomers, Diastereomers, Epimers Pyranose and furanose ring structures α- and β- anomers (Anomerism) 18 MONOSACCHARIDES: STRUCTURE Monosaccharides possess stereogenic centres: mostly carbon atoms that bind four different groups are often called ‘asymmetric (chiral)’ carbon atoms. All carbohydrates contain at least one asymmetrical (chiral) carbon. Exception: Dihydroxyacetone which has no chiral carbon. 19 MONOSACCHARIDES: STRUCTURE 20 MONOSACCHARIDES: STRUCTURE Glyceraldehyde (a chiral molecule) is used as the standard reference molecule. The presence of asymmetric carbon atoms confers optical activity. Rotates polarized light to the: right (D)- Dextrorotatory or to the left (L)- Levorotatory. D-glyceraldehyde and L-glyceraldehyde are stereoisomers. 21 MONOSACCHARIDES: STRUCTURE They differ in the configuration about the chiral carbon that is the furthest from the carbonyl carbon. 22 MONOSACCHARIDES: STRUCTURE Glyceraldehyde molecules are a type of stereoisomers called enantiomers; they are mirror images of each other. 23 MONOSACCHARIDES: STRUCTURE Diastereomers – pairs of isomers that have opposite configurations at one or more chiral centres but are not mirror images. 24 EPIMERS Are referred to diastereomers that differ in configuration at only one chiral (stereogenic) centre. Not mirror images. D-glucose and D-mannose are epimers which differ in configuration at C-2. D-glucose and D-galactose are epimers that differ in configuration at C-4. 25 MONOSACCHARIDES: STRUCTURE Pyranose and furanose ring structures: Monosaccharides are either pyran or furan. Six-membered ring monosaccharides: pyranoses. Five-membered ring monosaccharides: furanoses. 27 28 29 Some important monosaccharides Glucose (C6H12O6) – Most important simple carbohydrate in human metabolism. – Regulation of blood glucose is important in human health. Hormones: insulin and glucagon – Diabetes mellitus Some important monosaccharides Fructose (C6H12O6): fruit sugar - Structural isomer of glucose -Sweeter than glucose - Fructose intolerance leads to fructose accumulation and hypoglycaemia. 31 Some important monosaccharides Galactose (C6H12O6) – Major source: diary products -milk – Component of lactose (disaccharide) & glycoproteins found in brain and nerve tissue. – Galactosemia: excess galactose results in Cataract due to enzyme deficiency. Biological Significance Most of the monosaccharides in humans are D-sugars. There are some important sugars however, that occur in the L- form. For example, L-arabinose and L-fucose found in glycoproteins of plants and mammalian cells respectively. *NOTE: Only L-amino acids are used in protein synthesis. 33 Disaccharides- Chemical Bond Formed via condensation/dehydration reactions: - A H20 molecule is removed (condensation) from a pair of monosaccharide molecules when joined together. - The bond formed between 2 monosaccharides is called a glycosidic bond (O-glycosidic bond). Disaccharides may be hydrolyzed to form monosaccharide sub-units (reverse reaction). 34 35 DISACCHARIDES Two (2) monosaccharides joined = disaccharide Examples of disaccharides: Sucrose= glucose + fructose (table sugar) Maltose= glucose + glucose (used to make malted candy) Lactose = glucose + galactose (found in cow’s milk) 36 Examples of Disaccharides: Sucrose Commonly called “table sugar”. Composed of glucose and fructose through an α(1à2)β glycosidic bond. Highly sweet and soluble. 37 Example of a Disaccharide - Sucrose (non-reducing sugar) 38 Maltose Disaccharide with a α(1à4) glycosidic linkage between one glucose and a second glucose. It is called “malt sugar”. Intermediate product of the hydrolysis of starch. 39 40 Lactose Found exclusively in the milk of mammals, so it is called “milk sugar”. Consists of galactose and glucose in a β (1à4) glycosidic bond. It is less sweet and less soluble. 41 42 Oligosaccharides Oligo means “few” Contains 3-10 monosaccharide molecules which are liberated on hydrolysis. Functions include cell recognition and cell adhesion in the cell membrane. They are normally present as glycans: oligosaccharide chains are linked to lipids or to amino acid side chains in proteins, by N- or Oglycosidic bonds. 43 Blood groups ABO substances are oligosaccharides present in most cells of the body and in certain secretions. On the surface of red blood cells, three different types of oligosaccharides may be found. These help provide the ABO blood group determinants. 45 All have a chain of four sugars, they are written: gal - nag – gal – fuc which represents galactose, n-acetylglucosamine, and fucose. Fucose is a 6-carbon L-sugar. 46 Polysaccharides Large molecules > 10 monosaccharide units. Joined by O-glycosidic linkages in one continuous chain or the chain may be branched. 1. Storage polysaccharides: Contain only α- glucose units. e.g. starch and glycogen 2. Structural polysaccharides: Contain only β- glucose units. eg. cellulose and chitin. 47 POLYSACCHARIDE -STARCH Main food storage molecule of plants. Mixture of 2 polymers: amylose (20%) amylopectin (80%) Amylose: glucose units linked by α-1,4 glycosidic bonds. Long and unbranched Amylopectin: glucose units linked in short chains by α-1,4 glycosidic bonds. Branched every 24 - 30 glucose units Branches formed by 1,6 glycosidic bonds 48 Structure of Starch: Amylose & Amylopectin 1-4 bond 1-6 bond 1-4 bond 49 HOMOPOLYSACCHARIDES - GLYCOGEN Large, branched polymer of glucose residues that can be readily broken down to yield glucose molecules when energy is needed by the body. 50 GLYCOGEN **NOTE: The structure of glycogen is identical to amylopectin, except that the α-(1,6) branching occurs about every 12 glucose units. Other sugars of ‘importance’ D-ribose and D-2-deoxyribose are present in nucleic acids and are 5-carbon aldehyde sugars. Deoxyribose lacks the OH group at C-2 (β-deoxyribose). Ribose has a five-carbon chain and makes a furanose ring (5 membered ring). RIBOSE DEOXYRIBOSE 53 Heteropolysaccahrides Commonly called glycosaminoglycans (GAGs) or mucopolysaccharides. Long, unbranched chains generally composed of a repeating disaccharide unit (amino sugar-acidic sugar)n Amino sugar: D-acetyl glucosamine or D-galactosamine Acidic sugar: D-glucuronic acid or L-iduronic acid Examples: chitin, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate and heparin. 54 Examples: CHITIN Second most abundant polysaccharide in nature. Exoskeleton of crustaceans and insects: lobsters, beetles and spiders Made of N-acetylglucosamine containing: β (1--à4) glycosidic bonds. Chitin is used as surgical thread that biodegrades as a wound heals. 56 Hyaluronic acid (Hyaluronate) Long chains of modified glucose units are found in synovial fluid in joints, eye and in connective tissues (ligaments, cartilage, skin). Viscous molecule that provides lubrication and shock absorption. Heparin Polysaccharide polymer consisting of 2 types of monosaccharides: uronic acid and glucosamine It is an anticoagulant used in preventing blood clotting after surgery and in blood sample tubes. Chondroitin 6-sulphate Repeating disaccharide units composed of glucuronic acid and N-acetylgalactosamine. Chains are found in connective tissues, tendons and cartilage (also used in artificial skin). § Recommended for the prevention and management of osteoarthritis. 60