Carbohydrates Lecture Notes - BMS 100

Carbohydrates Dr. I. Fraser BMS 100 Objectives - Prelearning Define the different types of isomers and be able to classify pairs of monosaccharides according to their isomeric relationships With respect to monosaccharides, use D, L, alpha and beta designations correctly Describe the how mutarotation...

Carbohydrates Dr. I. Fraser BMS 100 Objectives - Prelearning Define the different types of isomers and be able to classify pairs of monosaccharides according to their isomeric relationships With respect to monosaccharides, use D, L, alpha and beta designations correctly Describe the how mutarotation works and the different monosaccharide structures it can produce Describe the various oxidation and reduction reactions of monosaccharides, and provide a physiological example of each Objectives - Monosaccharides Identify reducing sugars and describe the application of reducing sugars in diabetes mellitus Provide examples of monosaccharide esterifications and their physiological significance Recognize sugars that are glycosides, and provide an example and use for a cardiac glycoside Recognize important monosaccharide derivatives and their significance Carbohydrates Classification and Nomenclature Monosaccharides Prereading - Isomers - Cyclic structures - Redox reactions Esterification Glycoside formation Postreading: examples Important derivatives Disaccharides Reactions of Monosaccharides Redox reactions - prereading Esterification Glycoside formation Redox reactions review Oxidation can happen at the terminal CH2OH and/or aldehyde end of straight chain forms Reduction can happen at the aldehyde end of straight chain forms H C1 O H C1 H C 2 OH H C 2 OH HO C3 H O HO C3 H O O C 1 OH C 1 OH H C OH H C 2 OH H C 2 OH H C2 OH HO C 3 H HO C 3 H H HO 1 C3 H H C 4 OH H C 4 OH H C 4 OH H C 4 OH H C4 OH H C 5 OH H C 5 OH H C 5 OH H C 5 OH H C5 OH H C6 OH C6 OH H C 6 OH C 6 OH H C6 OH H D Glucose O H O H Redox Application: “Reducing Sugars” A “reducing sugar” is a sugar that can reduce a weak oxidizing agent Example: glucose Glucose reduces the oxidizing agent in the redox rxn below H C1 O O C 1 OH H C 2 OH HO C3 H H C 4 OH H C 2 OH + oxidizing reagent H C 5 OH H C6 OH H Glucose HO C 3 H H C 4 OH LEO: Loss of H+ on C = oxidation (also gain of O) + reduced oxidizing agent H C 5 OH H C 6 OH H Oxidized glucose Redox Application “Reducing sugars” Reducing sugars are any sugars capable of opening into the straight chain form Cannot have anything other than an OH attached to the anomeric C1 carbon Which of the following are reducing sugars? HO C H2 HO C H2 6 5 H 4 HO H 6 O H 1 OH 3 H H 2 OH OH 5 H 4 H O H 1 OH 3 H H 2 OH OCH3 Redox Application “Reducing sugars” Testing for sugar in the urine If a copper containing weak oxidizing reagent called Benedict’s solution is added to the urine, and if reducing sugars are present, the reagent turns a reddish brown colour when it is reduced Sugar in the urine can indicate the presence of diabetes mellitus (high blood sugar levels) Reactions of Monosaccharides Redox reactions - prereading Esterification Glycoside formation Esterification Sugar esterifications typically involve the formation of phosphate- or sulfate- esters. R Phosphate ester Monosaccharide Phosphate ester Sulfate esters Monosaccharide Sulfate ester R Esterification Monosaccharide phosphate esters A phosphate is a better leaving group than a hydroxyl, so adding a phosphate to a monosaccharide makes it more reactive What else can adding the phosphate do? O -O P OH C6O 5 O 2 H H H 1 4 H OH H OH O H3 2 OH Glucose 6-phosphate Esterification Monosaccharide sulphate esters The monosaccharides found in connective tissue (CT) are often sulfated At physiological pH, these sulfates become negatively charged These negative charges attract large amounts of water This makes CT less dense, so it can occupy 1000’s of time as much space than if packed tightly together! Negative charge at physiological pH R Reactions of Monosaccharides Redox reactions - prereading Esterification Glycoside formation Glycoside Formation Glycosides are sugars in which the OH group on the anomeric carbon is replaced by an alcohol, forming a glycosidic link HO C H2 6 5 H HO C H2 6 5 H 4 HO H O 1 OH 3 H H HO + CH3OH OH 3 H OH H + H2O OCH3 2 OH Methyl α-D-glucoside HO C H2 2 OH α (or ß) D-Glucose H 1 4 H H O 6 5 Methanol H 4 HO H O OCH3 1 OH 3 H H 2 + H2O H Methyl β-D-glucoside OH Glycosides as Heart Medications Below is a picture of a cardiac glycoside called digoxin -It is an extract from digitalis lanata -It is called a “cardiac” glycoside because: - It can improve the contraction of the heart - Useful for someone with congestive heart failure Alcohol attached to carbohydrate via glycosidic bond Carbohydrates Classification and Nomenclature Monosaccharides Prereading - Isomers - Cyclic structures - Redox reactions Esterification Glycoside formation Postreading: monosaccharide examples Important derivatives Disaccharides Postreading: Monosaccharide examples Glucose, fructose, galactose Recognize their structures! Post-reading material will be posted Carbohydrates Classification and Nomenclature Monosaccharides Prereading - Isomers - Cyclic structures - Redox reactions Esterification Glycoside formation Postreading: examples Important derivatives Disaccharides Monosaccharide Derivatives Deoxy sugars HO C H2 H H HO O Amino sugars HO C H2 OH H H H Deoxyribose 6 5 H 4 HO H O H 1 OH 3 H H OH 2 NH3+ D-glucosamine Deoxyribose What is the importance of deoxyribose? Amino sugars HO C H2 HO C H2 6 6 5 H 4 HO H OH 3 H O H H 5 H 1 4 OH HO 2 NH3+ H O H 1 OH 3 H H 2 OH O HNC-CH3 OH group is replaced by an amino group, which may also be acetylated - Common in complex biomolecules Carbohydrates Classification and Nomenclature Monosaccharides Prereading - Isomers - Cyclic structures - Redox reactions Esterification Glycoside formation Postreading: examples Important derivatives Disaccharides Objectives Provide the structural name for a disaccharide and its link Disaccharides Disaccharides are glycosides formed when two sugars join via a glycosidic link Maltose structural name: α-D-glucopyranosyl-(1 4)- β-D-glucopyranose Disaccharides Naming the molecule - The alpha and beta designations come from the OH positions at C1 of the first and second monosaccharide - The numeric designations come from the carbons associated with the glysosidic bond 1 α-D-glucopyranosyl-(1 4 4)- β-D-glucopyranose Disaccharides Naming the molecule Review: Where do you think the “gluco” parts of the name come from? What about the “pyranos(yl/e)”? Note from prereading: the “D” refers to the naturally occurring sugar in a mirror image pair. In the cyclic form, the terminal CH2OH points up if you have a “D” sugar. α-D-glucopyranosyl-(1 4)- β -D-glucopyranose Disaccharides Naming the glycosidic link -The name of glycosidic link in maltose is α(1,4) -The alpha/beta designation for the glycosidic link comes from the OH position at C1 of the first monosaccharide - The numeric designations come from the carbons associated with the glycosidic bond 1 4 Postreading Postreading slides provide practice on naming disaccharides and glycosidic links, and recognizing important derivatives They also include some information on important disaccharides Carbohydrates Previous slides: Monosaccharides, disaccharides Next: Oligosaccharides, polysaccharides – progressively larger sugars Last: Glycoconjugates - adding sugars to other molecules Objectives Differentiate oligosaccharides and polysaccharides Define homo- vs heteropolysaccharides and provide examples of each, including structure and function Define glycoprotein Differentiate glycoproteins and proteoglycans with respect to structure and function Oligosaccharides and Polysaccharides Oligosaccharides Small numbers (approx. 3-15) of monosaccharides linked by glycosidic bonds Often linked to proteins and lipids to form “glycoconjugates” Polysaccharides Larger numbers of monosaccharides linked by glycosidic bonds Polysaccharides Homopolysaccharides: Heteropolysaccharides: - Chains of all the same monosaccharides - Chains of two or more different monosaccharides Two functional categories: Function = structural 1) Storage - Starch (plants) - Amylose, Amylopectin - Glycogen (animals) Glycosaminoglycans (aka GAGs) (animals) 2) Structural - Cellulose (plants) Homopolysaccharides Storage polysaccharides: polymers of glucose in alpha links Starch: amylose, amylopectin PLANTS: Break starch back down to glucose when needed for ? ANIMALS: Ingest starch from plants and break it down to glucose during the digestive process Glycogen ANIMALS: Break glycogen back down to glucose when needed for energy Homopolysaccharides Storage Homopolysaccharides Starch (plants), glycogen (animals) Starch 2 types of polysaccharides Amylose: D-glucose in alpha (1,4) linkage Amylopectin: D-glucose in combination of alpha (1,4) + alpha (1,6) links Amylose B D-glucose in alpha (1,4) linkage A Unbranched D C Amylopectin D-glucose in combination of alpha (1,4) + alpha (1,6) links Branched E F Glucose is released from the non-reducing ends - Which are the reducing vs nonreducing ends? - What is the significance of the branches? See postreading for practice on reducing ends, non-reducing ends and branch points Homopolysaccharides Storage Homopolysaccharides Starch (plants), glycogen (animals) D-glucose in combination of alpha (1,4) + alpha (1,6) links Storage Homopolysaccharide Shape Overview Note that glycogen has more branch points that amylopectin. What is the significance of this? Postlearning We have now seen the storage polysaccharides in plants and animals In your postlearning you will find some slides on the structural polysaccharide, cellulose Heteropolysaccharides Heteropolysaccharides GAGs GAGs Found in cartilage, cornea, joints, etc Repeating disaccharide units (usually an acidic sugar plus an amino sugar) Heteropolysaccarides: GAGs Glycosaminoglycans: Examples Chondroitin sulfate Component of cartilage, tendons. bone Dermatan sulfate Component of skin Also found in other places, such as blood vessels, heart valves Heparin Component of mast cells, liver - anticoagulant Keratan sulfate Component of cornea, cartilage, intervertebral disks Hyaluronic acid Component of synovial fluid (found where?) and eye fluid (FYI: vitreous humor) GAG Structure Disaccharide units: Acidic and amino sugars Acidic sugar in most GAGs is glucuronic acid (FYI in all except keratin sulfate) Review: Glucuronic acid is an oxidized form of glucose O C= O HO C H2 6 5 H 4 HO H O 6 H 1 OH H 3 H 2 OH Glucose OH 5 H 4 HO H O H 1 OH 3 H H OH 2 OH Glucuronic Acid GAG Structure Disaccharide units: Acidic and amino sugars Amino sugar Either glucosamine or galactosamine HO C H2 HO C H2 6 5 H 4 HO H 6 O H 1 OH 3 H H 2 NH2 Glucosamine OH 5 HO 4 H H O H 1 OH 3 H H OH 2 NH2 Galactosamine GAG structure Disaccharide unites: More on amino sugars Often acetylated and sulfated HO C H2 HO C H2 6 6 5 HO H O 5 H 1 4 H OH 3 H H OH 2 NH2 HNCCH 3 -O SO 3 HO 4 H H O H 1 OH 3 H H OH 2 NH2 3 HNCCH O N-acetylgalactosamine N-acetylgalactosamine 4 sulfate GAG Structure Disaccharide units: Acidic and amino sugars The acid groups and sulfates have negative charges – what is the significance of this? HO C H2 O- 6 C= O 5 6 5 H 4 HO H O -O SO 3 HO H 1 OH 3 H H OH 2 OH Glucuronic Acid 4 H H O H 1 OH 3 H H OH 2 NH2 3 3 HNCCH HNCCH O N-acetylgalactosamine 4 sulfate Glycosaminoglycans Negative charges create: “Slippery” texture (think mucous), as GAGs “slide” past other due to charge repulsion A large volume, as GAGs are hydrated Resilience, as tissue can be “squished” when water is pushed out and “expanded” when water is able to return Resistance to pressure Collagen GAGs H2 O H2 O H2 O H2 O H2 O H2 O _- _- _ _ _ _ _ _ _ - - - - - - H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O _- _- _ _ _ _ _ _ _ - - - - - - H2 O H2 O H2 O H2 O PRESSURE H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O _- _- _ _ _ _ _ _ _ - - - - - - H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O _- _- _ _ _ _ _ _ _ - - - - - - - H2 O H2 O H2 O H2 O H2 O H2 O _- _- _ _ _ _ _ _ _ - - - - - - H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O H2 O _- _- _ _ _ _ _ _ _ - - - - - - H2 O H2 O H2 O H2 O H2 O H2 O Return to normal shape Postlearning Your postlearning will include pictures of the various GAGs and provide practice identifying their features Glycoconjugates Adding mono, di, oligo, or polysaccharides to other molecules creates glycoconjugates Examples: proteoglycans, glycoproteins, (glycolipids) How are carbohydrates attached to proteins? Via O- or N- glycosidic links O-Glycosidic Linkage HO C H2 6 5 H α D Glucose 4 HO H H Serine Group 1 OH 3 H A carbohydrate can attach to a protein though the “O” on a serine (or threonine) R-group O H OH CH2 HO 2 OH HO C H2 6 5 H 4 HO H O H 1 OH 3 H H 2 OH O CH2 O-Glycosidic linkage NANA Oligosaccharides are often attached to the OH of Ser or Thr via GalNAc Gal NANA Gal NAc O CH2 N C C H H H2N COOH N-Glycosidic Linkage HO C H2 6 5 α D Glucose H 4 HO H Asparagine Group H O 1 OH 3 H A carbohydrate can attach to a protein though the “N” on an asparagine Rgroup O H H2N OH C CH2 2 OH HO C H2 6 5 H 4 HO H O H 1 OH 3 H H 2 OH H O N C CH2 N-glycosidic linkage Gal Glc NAc Man Man Man Man Man Glc NAc Oligosaccharides are often attached to the amino group (N) of Asn via GlcNAc Glc NAc Glc NAc NH C O CH2 N C C H H O H2N COOH Glycoconjugates Proteoglycans Glycoproteins Type of sugar attached GAGs via O-link Mono, di, or oligosaccharides (but not GAGs) via O- or N-link Carb. content High (95%) Lower (1-85%) Glycoconjugates: Proteoglycans Proteoglycans consist of various GAGs (except hyaluronic acid) attached to core proteins via an Oglycosidic link The core proteins are then attached to a hyaluronic acid backbone Remember, the “protein” component of a “proteo”glycan is minimal GAG chains (“leaves”) link to core proteins (“branches”) that are then attached to a hyaluronic acid backbone (“trunk”) Glycoconjugates: Proteoglycans Physiology of Proteoglycans Located in extracellular matrix (ECM) Contribute support and elasticity to tissues For example, found in cartilage Known for its strength, flexibility, resilience Pathology of Proteoglycans See postreading for information on mucopolysaccaridosis Genetic disease associated with defective proteoglycan metabolism Glycoconjugates Proteoglycans Glycoproteins Type of sugar attached GAGs via O-link Mono, di, or oligosaccharides (but not GAGs) via O- or N-link Carb. content High (95%) Lower (1-85%) Glycoconjugates: Glycoproteins What types of monosaccharides are commonly found in the mono, di, or oligosaccharide attachments? N-acetylglucosamine, N-acetylgalactosamine, mannose, galactose What type of carbohydrate is not found on glycoproteins? Glycoconjugates: Glycoproteins Physiology of glycoproteins Often attached to membranes, projecting externally from the cell