MD138 Carbohydrates Lecture Notes Oct 2024 PDF

Introduction to Carbohydrates Dr Lynn O’Connor MD138 24-25 What are Carbohydrates? What are their functions? What is the involvement in Health and Disease?  What are they? Carbohydrates- the most abundant organic molecules in nature (“hydrate of carbon”) have...

Introduction to Carbohydrates Dr Lynn O’Connor MD138 24-25 What are Carbohydrates? What are their functions? What is the involvement in Health and Disease?  What are they? Carbohydrates- the most abundant organic molecules in nature (“hydrate of carbon”) have empirical formulas of (CH2O)n , where n≥3  What do they do? Dietary calories Storage form of energy in the body Components of cell membranes involved in intercellular communication Carbohydrate polymers – structural and protective elements in the connective tissue of animals Lubricate joints Participate in cell-cell recognition Complex CHO polymers covalently attached to lipid or proteins act as signals that determine the intracellular destination or metabolic fate of these hybrid molecules, called glycoconjugates Structural components of many organisms other than humans Cell walls of bacteria Exoskeleton of many insects Fibrous cellulose of plants Classification & Structure  Classification by the number of carbon atoms they contain Monosaccharides one monomeric unit Disaccharides two monomeric units Oligosaccharides ~3-10 monosaccharides Polysaccharides > 10 monosaccharides and can be hundreds Glycoconjugates linked to proteins or lipids  Classification by the type of carbonyl group CHOs with an CHOs with an aldehyde keto group as group as their their carbonyl carbonyl group are group are called ketones called aldoses CHOs with a free carbonyl group have the suffix –ose e.g glucose Ketoses have an additional “ul” in their suffix e.g. sedoheptulose Exceptions exist -fructose  Isomers & Epimers Isomers: same chemical formula, different structure C6H12O6 ; glucose, fructose, mannose and galactose Epimers: differ in configuration around one C (other than the carbonyl C)  Enantiomers Isomers that are mirror images of each other D- L- D- predominate in nature - Chemically identical but NOT biologically equivalent Note: Designated D- or L- by comparing their structures to D- and L- glyceraldehyde. In D- the OH grp on the asymmetric C farthest from the carbonyl C (C5) is on the right, while in the L- isomer it is on the left  Cyclization of monosaccharides Cyclization generates a new pair of isomers the  and  configuration which become anomers of each other 99% of monosaccharides exist cyclized  Diastereomers Anomeric carbon is derived from what was the carbonyl carbon A new pair of isomers is generated and named  and  forms of the sugar The  and  forms are not mirror images They are referred to as DIASTEREOMERS Video :https://www.khanacademy.org/science/organic- chemistry/stereochemistry-topic/diastereomers-meso- compounds/v/enantiomers-and-diastereomers – approx. 8 mins  Why are diastereomers important? Enzymes can and do distinguish between the forms – can work on one or the other preferentially e.g Glycogen is synthesized from -D-glucopyranose Cellulose is synthesized from -D-glucopyranose.  Thalidomide Drug used in the 1950’s for morning sickness in pregnant women Result-cases of congenital deformities rose –phocomelia At least 10.000 babies suffered malformations Why? Thalidomide exists as a mixture of optical isomers R – sedative properties –does alleviate symptoms of morning sickness S- Teratogenic agent Note: they can convert in solution  Reducing Sugars If the oxygen on the anomeric carbon of a sugar is NOT attached to any other structure – sugar can act as a reducing agent and is thus called a reducing sugar All Monosaccharides and most disaccharides are reducing sugars Examples: glucose, maltose, lactose Application: Colorimetric test for glucose in urine: Fehling’s reaction – diagnostic test for diabetes for many years Joining of Monosaccharides Monosaccharides can be joined to form more complex forms  Important disaccharides Sucrose Lactose Maltose  Monosaccharides to Polysaccharides Branched glycogen from animal sources Starch from plant Unbranched cellulose from plants ALL ARE POLYMERS OF GLUCOSE – glucose monomers are linked together by bonds called GLYCOSIDIC BONDS  Glycosidic bonds What are they? Bonds that link sugars together What enzymes catalyze them? Glycosyltransferases How do they work? They use nucleotide sugars such as uridine diphosphate (UDP) glucose as substrates  Linking monosaccharides Naming Glycosidic Bonds According to numbers of connected carbons Also with regard to the position of the anomeric hydroxyl group of the sugar involved in the bond. If the anomeric hydroxyl is in  config, the linkage is an -bond -  or   Complex carbohydrates Carbohydrates can be attached by glycosidic bonds to noncarbohydrates to form GLYCOSIDES and include purine and pyrimidine bases (found in nucleic acids) Aromatic rings ( e.g. steroids and bilirubin) proteins (found in glycoproteins and proteoglycans) Lipids (found in glycolipids) N- and O-glycosides If the group on the noncarbohydrate molecule to which the sugar is attached is an –NH2 group the structure is an N-glycoside Bond is an N-glycosidic link the group on the noncarbohydrate molecule to which the sugar is attached is an –OH group the structure is an O-glycoside Bond is an O-glycosidic link  The Sugar Code: Carbohydrates as Informational Molecules: Monosaccharides can be assembled into an almost limitless variety of oligosaccharides – glycans -more information- dense than nucleic acids or proteins Lectins – proteins with highly specific CHO-binding domains (a glycan code), are commonly found on the outer surface of cells, where they initiate interactions with other cells. In vertebrates, oligosaccharide tags are “read” by lectins -govern the rate of degradation of certain peptide hormones, circulating proteins and blood cells  The Sugar Code: Carbohydrates as Informational Molecules: Lectins are proteins that read the sugar code and mediate many biological process Cell surface lectins (both human and the lectins of infectious agents) important in the development of some diseases Human selectins mediate the inflammatory responses in Rheumatoid arthritis Asthma Psoriasis MS Rejection of transplanted organs Major interest in development of drugs that mediate selectin- mediated cell adhesion  2 glucose – 11 possible different isoforms 2 different monosaccharides – 20 isoform Vs 2 amino acids – one possible combination The role of oligosaccharides in recognition events at the cell surface and in the endomembrane system Glycans label our own cells and identify them as ‘self’ The sugars on our cells and on bacterial cells label them as friend or foe  What you should know at the end of this lecture Know what a carbohydrate is by definition, identify some of the multiple functions Distinguish between mono-, di- and poly-saccharides and be able to give examples of each Know the monomeric constituents of the 3 common disaccharides mentioned here Be able to define isomers, epimers,enantiomers ,anomers and diastereomers and if presented with the fig in slide 10 for example be able to identify the epimers and isomers What is the functional significance of all the various forms of carbohydrate Know what type of bond holds CHO to other CHO and to other non-carbohydrate molecules Be clear about the composition and branching of common polysaccharides, how they are distinguished and how does that matter functionally Know what a reducing sugar is and be able to give an example Know the value in medicine of identifying reducing sugars What is the sugar code, what reads the code and where might this functionality be evident Note: look the diagrams used in this lecture. If the labels were removed could you identify the key features – you do not need to memorize structures of sugars etc but e.g if you were given the fig in slide 10 without the labels telling you which was an aldehyde and which was a ketone could you identify them? You should be able to do this.