STRUCTURE AND FUNCTION OF CARBOHYDRATES (SUGARS) Azin Nowrouzi (PhD)

Overview: The Molecules of Life All living things are made up of four classes of large biological molecules: 1.Carbohydrates 2.lipids 3.Proteins 4.nucleic acids Within cells, small organic molecules are joined together to form larger molecules Macromolecules are large molecules composed of thousands of covalently connected atoms Molecular structure and function are inseparable Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Many Important Biomolecules are Polymers monomer polymer supramolecular structure lipidsproteinscarbonucleic acids

A condensation reaction or more specifically a dehydration reaction occurs when two monomers bond together through the loss of a water molecule Enzymes are macromolecules that speed up the dehydration process Polymers are disassembled to monomers by hydrolysis, a reaction that is essentially the reverse of the dehydration reaction The Synthesis and Breakdown of Polymers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 5-2 Short polymer HO 123H H Unlinked monomer Dehydration removes a water molecule, forming a new bond HO H2OH2O H Longer polymer (a) Dehydration reaction in the synthesis of a polymer HO H H2OH2O Hydrolysis adds a water molecule, breaking a bond HO H H (b) Hydrolysis of a polymer

Fig. 5-2a Dehydration removes a water molecule, forming a new bond Short polymerUnlinked monomer Longer polymer Dehydration reaction in the synthesis of a polymer HO H2OH2O H H H (a)

Fig. 5-2b Hydrolysis adds a water molecule, breaking a bond Hydrolysis of a polymer HO H2OH2O H H H (b)

Carbohydrates (sugars) Most abundant macromolecules in nature Functions: Energy Storage Structure Cellular Recognition DNA Backbone

Classification of Sugars Monosaccharides simple sugars Polyalcohols Aldehyde, ketone Common formula: (CH2O)n = CnH2nOn when n≥3 They contain C, H, and O Monosaccharides are classified by three characteristics: ①The location of the carbonyl group (as aldose or ketose) ②The number of carbons in the carbon skeleton (Based on number of carbons (3, 4, 5, 6), a monosaccharide is a triose, tetrose, pentose or hexose. ③Chiral handedness Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings  Disaccharides - 2 monosaccharides covalently linked.  Oligosaccharides - a few monosaccharides covalently linked.  Polysaccharides - polymers consisting of chains of monosaccharide or disaccharide units.

Aldotriose Ketotriose Aldotetrose Ketotetrose Aldopentose Ketopentose ….

Aldoses

Enantiomers = mirror images

D vs L Designation enantiomers = mirror images D & L designations are based on the configuration about the single asymmetric C in glyceraldehyde. The lower representations are Fischer Projections.

Optical activity measured by polarimeter Temperature T (given in degrees Celsius) and wavelength λ (in nanometers). If the wavelength of the light used is 589 nanometer (the sodium D line), the symbol “D” is used. Some examples: Sucrose ° Lactose +52.3° Cholesterol −31.5° Penicillin V +223° Fructose degrees Glucose degrees

D-Aldose Tree

Carbohydrates - Stereochemistry For sugars with more than one chiral center, D or L refers to the asymmetric C farthest from the aldehyde or keto group. Most naturally occurring sugars are D isomers. put most oxidized carbon at top continue carbon chain to bottom non-hydrogen substituent on right=D The number of stereoisomers is 2 n, where n is the number of asymmetric centers.

Optical activity Racemic solution Meso compound

Simple ketoses Ketotetrose Ketopentose Ketohexoses: D-fructose -Fructose helps add to your weight. -Can cause you to have a chance in getting diabetes. -Can cause blood clots -Can damage the liver -Weakens the immune system

Cyclic sugar structures; Haworth projections internal hemiacetal formation an alcohol group adds to the carbonyl

Hemiacetal & hemiketal formation An aldehyde can react with an alcohol to form a hemiacetal. A ketone can react with an alcohol to form a hemiketal.

Hemiacetal formation (mechanism)

Cyclization of glucose produces a new asymmetric center at C1. The 2 stereoisomers are called anomers,  & . Haworth projections represent the cyclic sugars as having essentially planar rings, with the OH at the anomeric C1:   (OH below the ring)   (OH above the ring).

furanose: a 5-membered ring pyranose: a 6-membered ring

Because of the tetrahedral nature of carbon bonds, pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar. The representation above reflects the chair configuration of the glucopyranose ring more accurately than the Haworth projection. β-D-Glucopyranose = +19  α-D-Glucopyranose = +112  At equilibrium = +52°

Mutarotation of glucose the two stereoisomers at the hemiacetal (anomeric) carbon alpha anomer: OH group is down (Haworth) beta anomer: OH group is up (Haworth) anomers are diastereomers (different physical properties)

Fructose forms either  a 6-member pyranose ring, by reaction of the C2 keto group with the OH on C6, or  a 5-member furanose ring, by reaction of the C2 keto group with the OH on C5.

Glycosylation Glycosidic bond a glycosidic bond is a type ofcovalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate Methyl α-D-glucopyranoside O-glycoside N-glycoside

Glycosylation of hemoglobin

Sugar derivatives  sugar alcohol - lacks an aldehyde or ketone; e.g., ribitol.  sugar acid - the aldehyde at C1, or OH at C6, is oxidized to a carboxylic acid; e.g., gluconic acid, glucuronic acid.

Sugar derivatives

Reduction of Aldehyde or ketone

Oxidation of alcohol at C-6

Oxidation of aldehyde group

Oxidation at both ends

Deoxy sugars L-Rhamnose

Amino sugars amino sugar - an amino group substitutes for a hydroxyl. An example is glucosamine. The amino group may be acetylated, as in N-acetylglucosamine.

N-acetylneuraminate (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH, as shown here.

Sialic acid Metastatic cancer cells often express a high density of sialic acid- rich glycoproteins. This overexpression of sialic acid on surfaces creates a negative charge on cell membranes. This creates repulsion between cells (cell opposition) and helps these late-stage cancer cells enter the blood stream.

Phosphate ester derivative

Sulfate esters D-Galactose 4-sulfate sodium salt

Glycosaminoglycans (GAGs) or Mucopolysaccharides Heteropolysaccharides long unbranched heteropolysaccharides Consist of a repeating disaccharide unit Repeating disaccharide unit = a hexose (or hexouronic acid linked to a hexosamine. In the Golgi apparatus, GAG disaccharides are added to protein cores to yield proteoglycans except hyaluronan

Hyaluronic acid 1T3 glycosidic bonds in b configuration The repeating disaccharides are linked by 1T4 linkages in b configuration

IdoUAβ1-3'GalNAcβ1-4 -Gal(6S)β1-4GlcNAc(6S)β1-3 GlcUAβ1-3'GalNAcβ1-4

Chondroitin Sulfate GlcUAβ1-3'GalNAcβ1-4 D-glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc).

Types of chondroitin sulfate "Chondroitin sulfate B" is an old name for dermatan sulfate, and it is no longer classified as a form of chondroitin sulfate.

Dermatan sulfate Dermatan sulfate is a glycosaminoglycan Distinguished from chondroitin sulfate by the presence of iduronic acid It was called a mucopolysaccharide Is found mostly in skin, also in blood vessels, heart valves, tendons, and lungs May have roles in coagulation, cardiovascular disease, carcinogenesis, infection, wound repair, and fibrosis IdoUAβ1-3'GalNAcβ1-4

Keratan sulfate Keratan sulfate (KS), also called keratosulfate any of several glycosaminoglycans (structural carbohydrates) that have been found in the cornea, cartilage, and bones It is also synthesized in the central nervous system Participate both in development and in the glial scar formation after injury Are highly hydrated molecules which in joints can act as a cushion to absorb mechanical shock The basic repeating disaccharide unit within keratan sulfate is -3Galβ1- 4GlcNAcβ1- Keratan sulfate occurs as aproteoglycan (PG) in which the chains are attached to cell-surface proteoglycan (PG) in which KS chains are attached to extracellular matrix proteins, termed core proteins -Gal(6S)β1-4GlcNAc(6S)β1-3

Heparin a highly sulfated glycosaminoglycan widely used as an injectable anticoagulant Highest negative charged density of any known biological molecule One unit of heparin (the "Howell Unit") is an amount approximately equivalent to mg of pure heparin, which is the quantity required to keep 1 mL of cat's blood fluid for 24 hours at 0 °C -IdoUA(2S)α1-4GlcNS(6S)α1-

Proteoglycan

Cellulose