D_03 Carbohydrates 2024 PDF

Unit 3: Carbohydrates 1. Structures and names of carbohydrates 2. Biological properties and functions of mono‐, di‐ and poly‐saccharides 3. Biological function of gly...

Unit 3: Carbohydrates 1. Structures and names of carbohydrates 2. Biological properties and functions of mono‐, di‐ and poly‐saccharides 3. Biological function of glycoconjugates 1  Carbohydrates  Named so because many have Cn(H2O)n  Produced from CO2 and H2O via photosynthesis in plants  Range from as small as glyceraldehyde (Mw = 90 g/mol) to as large as amylopectin (Mw = 200,000,000 g/mol)  Sugar stereoisomers arise because many of the carbon atoms to which the hydroxyl groups are attached are chiral centers  Enzymes that act on sugars are stereospecific  Can be covalently linked with proteins to form glycoproteins and proteoglycans  Fulfill a variety of functions including: energy source and energy storage structural component of cell walls and exoskeletons informational molecules in cell‐cell signaling 2  Principle Carbohydrates can have multiple chiral carbons; the configuration of groups around each carbon atom determines how the compound interacts with other biomolecules. With rare exceptions, biological evolution selected one stereochemical series (D‐series) for sugars.  Monosaccharides Have Asymmetric Centers all monosaccharides (except dihydroxyacetone) contain 1+ chiral carbon atom – occur in optically active isomeric forms enantiomers = two different optical isomers that are mirror images most frequent the D‐series  What Makes Sugar Sweet? TAS1R2 and TAS1R3 encode sweet‐taste receptors binding of a compatible molecule generates a “sweet” electrical signal in the brain – requires a steric match  Principle Monomeric subunits, monosaccharides, serve as the building blocks of large carbohydrate polymers. The specific sugar, the way the units are linked, and whether the polymer is branched determine its properties and thus its function.  Carbohydrates  Monosaccharides = simple sugars, consist of a single polyhydroxy ‐aldehyde or ‐ketone unit example: D‐glucose  Disaccharides = oligosaccharides with two monosaccharide units example: sucrose (D‐glucose and D‐fructose)  Oligosaccharides = short chains of monosaccharide units, or residues, joined by glycosidic bonds  Polysaccharides = sugar polymers with 10+ monosaccharide units examples: cellulose (linear), glycogen (branched) 7  Aldoses and ketoses  An aldose contains an aldehyde functionality  A ketose contains a ketone functionality 8  Standard sugars  Ribose is the standard five‐carbon sugar  Glucose is the standard six‐carbon sugar  Galactose is an epimer of glucose Epimers are two sugars that differ only in the configuration around one carbon atom  Fructose is the ketose form of glucose 9 Cyclic structure of monosaccharides  Pentoses and hexoses readily form intramolecular cyclic structures  The former carbonyl carbon becomes a new chiral center, called the anomeric carbon  The former carbonyl oxygen becomes a hydroxyl group; the position of this group determines if the anomer is  or   The hydroxyl group on the anomeric carbon can act as a reducing agent 10  Organisms Contain a Variety of Hexose Derivatives some sugar intermediates are phosphate esters example: glucose 6‐phosphate aldonic acids = form following oxidation of the carbonyl carbon of aldoses uronic acids = form following oxidation at C‐6 both form stable intramolecular esters called lactones  Colorimetric Glucose Analysis -D-Glucose -D-Gluconolactone CH2OH Enzymatic methods are used to CH2OH quantify reducing sugars such as O OH O Glucose oxidase glucose OH OH O HO HO – The enzyme glucose oxidase OH O2 OH catalyzes the conversion of glucose to glucono‐‐lactone and H 2 O2 hydrogen peroxide NH OCH3 NH2 – Hydrogen peroxide oxidizes 2 H2 O OCH3 organic molecules into highly colored compounds – Concentration of such Peroxidase compounds is measured OCH3 colorimetrically NH OCH3 NH2 Electrochemical detection is used in Oxidized Reduced portable glucose sensors o-dianisidine o-dianisidine (bright orange) (faint orange) 12  Principle Monomeric subunits, monosaccharides, serve as the building blocks of large carbohydrate polymers. The specific sugar, the way the units are linked, and whether the polymer is branched determine its properties and thus its function.  Disaccharides are formed by a Glycosidic Bond  Two monosaccharides can be linked via a glycosidic bond between an anomeric carbon and a hydroxyl carbon  The disaccharide formed upon condensation of two glucose molecules via 1 4 bond is called maltose  Two sugar molecules can be also linked via a glycosidic bond between two anomeric carbons  There are no reducing ends, this is a nonreducing sugar 14 Natural carbohydrates are usually found as Polysaccharides  Polysaccharides can be: Homopolysaccharides / heteropolysaccharides Linear / branched  Polysaccharides do not have a defined molecular weight  Also called glycans 15 Starch and Glycogen are storage forms of fuel Glycogen is a branched homopolysaccharide of glucose  Glucose monomers form (1 4) linked chains  Branch‐points with (1 6) linkers every 8–12 residues  Molecular weight reaches several millions  Functions as the main storage polysaccharide in animals (forms granules)  One reducing end and many nonreducing ends  Enzymatic processing occurs simultaneously in many nonreducing ends 16 Starch and Glycogen are storage forms of fuel Starch contains 2 types of glucose polymers:  Amylose: Long unbranched chains of monomers with (1 4) bonds  Amylopectin: Even longer chains of monomers with (1 4) bonds (1 6) branch points every 24‐30 monomers 17  Digestion of dietary carbohydrates  Glycosidases present in the mouth and intestinal lumen – Hydrolyse glycosidic bonds – Specific for structure and configuration  Salivary ‐amylase – Acts on random (1→4) bonds of starch (plants) and glycogen (animals) – Leaves short branched and unbranched oligosaccharides: dextrins – Inactivated by the stomach acid pH  Pancreatic ‐amylase – Active in the small intestine after the pH is neutralised  Intestinal disaccharidases – Transmembrane proteins on the luminal surface of the intestinal mucosa cells – Specific enzymes release reducing monosaccharides  Monosaccharides are absorbed in the small intestine – Energy –dependent and –independent transporters – Transported from the intestinal mucosa cells into the portal circulation  Abnormal degradation of disaccharides causes diarrhoea – Disaccharidase deficiency (acquired or inherited) causes the passage of indigested carbohydrates into the large intestine – Water is drawn from the mucosa (osmotically active material) – Lactose intolerance in 70% of the world’s adult population 18  Principle An almost infinite variety of discrete structures can be built from a small number of monomeric subunits. Even short polymers, when arranged in different sequences, joined through different linkages, and branched to specific degrees, present unique faces recognized by their molecular partners.  Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix Glycosaminoglycans: Linear polymers of repeating disaccharide units hyaluronan (hyaluronic acid) = alternating residues of D‐ glucuronic acid and N‐acetylglucosamine chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparan sulfate Extracellular matrix (ECM)  Gel‐like material in the extracellular space of tissues that holds cells together and provides a porous pathway for nutrient and O2 diffusion  Provides strength, elasticity, and physical barrier in tissues  Connective tissue and lubrication of joints  Main components Glycosaminoglycans Proteoglycan aggregates Collagen fibers Elastin (a fibrous protein) 20 Glycoconjugates: biologically active molecules consisting of an informational carbohydrate joined to a protein or lipid  Glycoconjugates Proteoglycans: sulfated glycosaminoglycans attached to large proteins in cell membrane – Interact with a variety of receptors from neighbouring cells and regulate cell growth – Proteoglycan aggregates (Hyaluronan) are main components of the Extra Cellular Matrix (ECM) Cover joint surfaces: articular cartilage Glycoproteins: proteins with small oligosaccharides attached – About half of mammalian proteins are glycoproteins – Carbohydrates play a role in protein‐protein recognition – found on the outer face of the plasma membrane, in ECM, in blood, and in organelles (Golgi complexes, secretory granules, and lysosomes) – Viral proteins heavily glycosylated; helps evade the immune system 22  Glycoconjugates Glycolipids: plasma membrane components in which the hydrophilic head groups are oligosaccharides – Parts of plant and animal cell membranes – In vertebrates, ganglioside carbohydrate composition determines blood groups Glycosphingolipids: class of glycolipids with specific backbone structure – Neurons are rich in glycosphingolipids – Play a role in signal transduction 23  Principle Molecular complementarity is central to function. The recognition of oligosaccharides by sugar‐binding proteins (lectins) results from a perfect fit between lectin and ligand. Role of Lectin‐Ligand Interactions in Leukocyte Movement Biological Interactions Mediated by the Sugar Code