Parvin Pasalar Arsia Jamali Tehran University of Medical Sciences

Why Carbohydrates ?

Sugars Objectives: After studying this session you have to: Objectives: After studying this session you have to: Define what a carbohydrate molecule is Define what a carbohydrate molecule is Recognise and classify carbohydrate molecules Recognise and classify carbohydrate molecules Explain why carbohydrates are important Explain why carbohydrates are important Explain different types of isomerism in monosaccharides Explain different types of isomerism in monosaccharides Name other molecules that interact with carbohydrates and explain how and why these interactions occur Name other molecules that interact with carbohydrates and explain how and why these interactions occur Know different names, roles, definitions, structurs and classifications of sugars, MS, OS(DS) & PS Know different names, roles, definitions, structurs and classifications of sugars, MS, OS(DS) & PS

Sugars/ Importance 1. Photosynthesis energy stored in carbohydrates 1. Photosynthesis energy stored in carbohydrates 2. The most abundant organic molecules in nature 2. The most abundant organic molecules in nature 3. Metabolic precursors of all other biomolecules 3. Metabolic precursors of all other biomolecules 4. Central in the metabolism of plants and animals 4. Central in the metabolism of plants and animals 5. Important structural component of plants (cellulose, pectate), animals (hyaloronic acid, chitin) and bacterial cells (murein) 5. Important structural component of plants (cellulose, pectate), animals (hyaloronic acid, chitin) and bacterial cells (murein)

Sugars/ Importance 6. Fuel; In animals, they represent a major part of the caloric intake. 6. Fuel; In animals, they represent a major part of the caloric intake. 7. Energy Storage ( glycogen, starch, inulin). 7. Energy Storage ( glycogen, starch, inulin). 8. Cell-cell recognition 8. Cell-cell recognition 9. Adhesion (hyaluronic acid) 9. Adhesion (hyaluronic acid) 10. They are important in immune responses either as antigenic determinants or antibody structure 10. They are important in immune responses either as antigenic determinants or antibody structure 11. Protein ageing ( non-enzymatic glycation) 11. Protein ageing ( non-enzymatic glycation) 12. Age determinant in some protein and cells (Asialo glycoprotein) 12. Age determinant in some protein and cells (Asialo glycoprotein) Sugars/ Importance

Sugars/ Different names and definition 1- Carbohydrates { Cn(H 2 O)n }: Substances with equal ratio of carbon atom and water. 1- Carbohydrates { Cn(H 2 O)n }: Substances with equal ratio of carbon atom and water. Exceptions: Exceptions: *Sugars that have not the formula (deoxyribose & Fucose) *Sugars that have not the formula (deoxyribose & Fucose) *Substances that are not sugars but have the formula { formaldehyde (C H 2 O) & lactic acid {C3(H 2 O)3} *Substances that are not sugars but have the formula { formaldehyde (C H 2 O) & lactic acid {C3(H 2 O)3}

Sugars/ Different names and definition 2- Glucides ( glycos= Gk. sweet) OR 2- Glucides ( glycos= Gk. sweet) OR Saccharides ( sakcharon= Gk. sugar) Saccharides ( sakcharon= Gk. sugar) Exceptions: Exceptions: *Sugars that are not sweet (cellulose & starch) *Sugars that are not sweet (cellulose & starch) *Sweet substances that are not sugars (glycerol, monilin, aspartam and saccharine) *Sweet substances that are not sugars (glycerol, monilin, aspartam and saccharine) 3- Ose ( suffix from Fr. sugar) 3- Ose ( suffix from Fr. sugar) 4- Definition: Polyhydroxy compound with an aldehyde or a ketone group or those compounds that by hydrolysis produce such compounds. 4- Definition: Polyhydroxy compound with an aldehyde or a ketone group or those compounds that by hydrolysis produce such compounds.

Sugars Different classifications: Different classifications: 1- With respect to the number of building blocks they are classified into three groups: 1- With respect to the number of building blocks they are classified into three groups: a-Monosaccharide (mono= one) or simple sugar have just one unit. a-Monosaccharide (mono= one) or simple sugar have just one unit. b-Oligosaccharide (oligo= few) that are composed of 2-10 Monosaccharide units b-Oligosaccharide (oligo= few) that are composed of 2-10 Monosaccharide units c-Polysaccharides (poly = many) are much larger sugars, containing hundreds of monosaccharide units c-Polysaccharides (poly = many) are much larger sugars, containing hundreds of monosaccharide units 2- With respect being pure sugar or having other components are classified into: 2- With respect being pure sugar or having other components are classified into: a- Glycoprotein & Proteoglycane a- Glycoprotein & Proteoglycane b- glycolipid and lipopolysccharide. b- glycolipid and lipopolysccharide.

Sugars/General idea The simplest sugar is Glyceraldehyde. The simplest sugar is Glyceraldehyde. All other simple sugars are derived from Glyceraldehyde. All other simple sugars are derived from Glyceraldehyde. The structure of Glyceraldehyde is the basis of sugar classification into two different D or L classes. The structure of Glyceraldehyde is the basis of sugar classification into two different D or L classes.

They have asymmetric (chiral) carbon. They have asymmetric (chiral) carbon. The only sugar that has not any The only sugar that has not any assymetric carbon is dihydroxyacetone. Glucose ( dextrose) is the reference sugar in medical sciences and is the most abundant sugar that is present and used as the fuel in all living organisms. Glucose ( dextrose) is the reference sugar in medical sciences and is the most abundant sugar that is present and used as the fuel in all living organisms. Sugars/General idea

MS/ Different definitions They are called simple sugar, because by hydrolysis they can not make any other simpler sugars. They are called Polyhydroxyaldehyde or Polyhydroxyketone. In other words: They are Polyhydroxy compound with an aldehyde or a ketone group.

Monosaccharides Different Classifications and nomenclatures: Different Classifications and nomenclatures: 1- On the basis of the numbers of carbon atoms: Triose, tetrose, pentose, hexose and heptose. 1- On the basis of the numbers of carbon atoms: Triose, tetrose, pentose, hexose and heptose. 2- On the basis of the functional group: Aldose and ketose. In most cases the name of a ketose is make by addition of “ ul ” between the name of sugar and ose. Example: Ribose and ribulose, heptose and heptulose. 2- On the basis of the functional group: Aldose and ketose. In most cases the name of a ketose is make by addition of “ ul ” between the name of sugar and ose. Example: Ribose and ribulose, heptose and heptulose. 3-On the basis of both above properties: Aldotriose, ketotriose. 3-On the basis of both above properties: Aldotriose, ketotriose.

Monosaccharides Different properties and roles : Different properties and roles : 1- They are composed of 3-7 (3-8) carbon atoms 2-All are soluble, reducing and easily can make crystal. 3- D- family sugars are the most abundant sugars in the living organism. 4-Because of the functional groups (aldo, keto and hydroxyl groups they are reactive compounds

6- By becoming cyclic, 5-7 carbon sugars are called internal hemiacetal or hemiketal. In other words they are produced by joining of the functional group with a hydroxyl group of same molecule. 7- By combination they make oligo and polysaccharides. 8-There are different isomerisms for the MS MS/ Different properties and roles

MS/ Asymmetric (chiral) carbon Chiral means like hands. It is referred to a carbon atom with 4 different groups linked to it.

Two different 1- methyl glucoside of Glc !

Sugars/ General structure/ Cyclization

Sugars/ Cyclic (Ring) structure A: Haworth projection

Monosaccharides Different isomerisms: Different isomerisms: * Functional * Functional * Ring * Ring * Optic * Optic

MS/ isomerisms/1- Functional * Aldose is referred to those simple sugars that have an aldehyde group as their functional group. * Ketose is referred to those simple sugars that have an ketone group as their functional group. Aldose to ketose conversion by enediol intermediate

MS/ isomerisms/Functional

MS/ isomerisms/ 2- Ring * By the linking of functional group to a hydroxyl group, 4-7 carbon sugars make a furan or pyran like rings. In this way, the carbon of functional group is called anomeric carbon. Pyranose is a six member ring Pyranose is a six member ring sugar that may be in chair sugar that may be in chair or boat conformation. or boat conformation. Furanose is a five member ring Furanose is a five member ring sugar that its conformation sugar that its conformation is like a letter envelope. is like a letter envelope. Note that: Linear and cyclic sugars are isomers. Note that: Linear and cyclic sugars are isomers.

MS/ Isomerisms Furanose/ PyranoseChair/ Boat Ring Conformational

MS/ isomerisms/3- Optic or Steroisomerism It is because of the presence of asymmetric carbon atom and is classified into four types: It is because of the presence of asymmetric carbon atom and is classified into four types: * D & L * D & L * Enantiomerism * Enantiomerism * Epimerism * Epimerism * Anomerism * Anomerism

MS/ isomerisms/Streoisomerism( Optic) a- Enantiomerism b- Epimerism c- Anomerism

* D & L do not refer to the rotation of polarized light, but are stand for the family of the sugar. For showing the rotation of polarized light (+) or (- )sign are used. * D- family sugars are abundant, natural sugars that are derived from D- glyceraldehyde so the OH group of the last asymmetric atom is at right.. * L- family sugars are rear sugars and just found in the oligosaccharides present as antigenic moieties. They can not be metabolized and make energy. The OH group of the last asymmetric atom is at left. 1- D & L MS/ isomerisms/3- Optic/ 1- D & L

* Definition: * All OH groups have opposite orientation * A pair of enantiomers have same name, but are shown with D or L letters. * They rotate polarized light equally into two opposite directions, if one is D(-) the other one will be L(+). Example: D(+) Glc & L(-) Glc or D(+)Fru & L(-) Fru MS/ isomerisms/3- Optic/ 2- Enantiomerism ( mirror image)

Definition: The difference between the OH orientation of just one asymmetric carbon atom other than the last one (the one that determines the family of a sugar). Definition: The difference between the OH orientation of just one asymmetric carbon atom other than the last one (the one that determines the family of a sugar). Example: Example: Mannose ( epimer 2 Glc) Mannose ( epimer 2 Glc) Allose ( epimer 3 Glc) Allose ( epimer 3 Glc) Galactose ( epimer 4 Glc) Galactose ( epimer 4 Glc) 3- Epimerism MS/ isomerisms/3- Optic/ 3- Epimerism

Definition: Definition: * OH orientation of anomeric carbon is the basis of this classification. * OH orientation of anomeric carbon is the basis of this classification. β anomer : Same orientation with the side chain β anomer : Same orientation with the side chain ( the last carbon atom) ( the last carbon atom) α anomer : opposit orientation with the side chain α anomer : opposit orientation with the side chain Example: α or β anomer of D(+)Glc. Example: α or β anomer of D(+)Glc. 4- Anomerism MS/ isomerisms/3- Optic/ 4- Anomerism

MS/ isomerisms/ optic / Mutarotaion Mutarotaion: α or β anomer can convert to each other via an open chain intermediate. In doing so the degree of polarized light rotation changes. Mutarotaion: α or β anomer can convert to each other via an open chain intermediate. In doing so the degree of polarized light rotation changes. At equilibrium 1/3 will be α and 2/3 will be β anomer. At equilibrium 1/3 will be α and 2/3 will be β anomer.

MS/ Chiral carbon & optic isomer number For each chiral center there are two optic isomers. For each chiral center there are two optic isomers. They are not superimposable. They are not superimposable. The number of chiral carbon in: The number of chiral carbon in: Linear aldoses: n= N-2 so linear Glc has 2 4 optic isomers Linear aldoses: n= N-2 so linear Glc has 2 4 optic isomers Cyclic aldoses: n=N-1 so cyclic Glc has 2 5 optic isomers Cyclic aldoses: n=N-1 so cyclic Glc has 2 5 optic isomers Linear ketoses: n= N-3 so linear Fru has 2 3 optic isomers Linear ketoses: n= N-3 so linear Fru has 2 3 optic isomers Cyclic ketoses: n= N-2 so cyclic Fru has 2 4 optic isomers Cyclic ketoses: n= N-2 so cyclic Fru has 2 4 optic isomers

Isomers Enantiomers are mirror image Configurational Ketose Steroisomers Same atom connectivity different arrangement in pace Functional Isomers different atom connectivity Aldose Conformational Diasteromers are not mirror image (epimers) BoatChair Anomers OPTIC Ring FuranPyran Envelop

MS/Different reactions: *Oxidation*Reduction *Ester formation *Amination *Glycoside formation

MS/ Reactions/Oxidation 1: Aldonic acid: Oxidation of aldehyde Group.Example: Gluconic acid. 2: Uronic acid: Oxidation of primary alcohol group. Example: glucoronic acid. 3: Aldaric acid: Oxidation of aldehyde and primary alcohol group Example: Glucaric acid ( saccharic acid), Mannaric acid ( arabic gum) Galactaric acid (mucic acid)

MS/ Reactions/Oxidation 4: Furfural formation Oxidation and dehydration of M.S by very strong acids Example: Furfural from pentoses and hydroxymethyl furfural from hexoses

MS/ Reactions/ Reduction 1-Polyalcohols * Reduction by gaining hydrogen Example: Sorbitol from glucose, fructose and mannose 2- Deoxysugars *Reduction by losing oxygen = deoxysugar formation Example: Deoxyribose form ribose, Fucose from L-galactose

Examples of Polyalcohols Examples of Deoxysugars

MS/ Reactions/ Amination Amino sugars: Glucosamine, mannosamine N- acetyl amino sugars : N- acetyl glucosamine, N- acetyl mannosamine Sialic acids: NAM+ PA Glc A Man A Gal A NAG

MS/ Reactions/ Ester formation * Phosphate esters: have an important role in metabolism. Example: G6P, G1, 6 bis P, R5P. *Sulfate esters: of sugars are found in the glycosaminoglycanes (GAG). Example: Gal 6 sulfate, Gal 4 sulfate.

MS/ Reactions/ Glycoside formation * O- glycoside compounds: acetal or ketal are formed by combination of an alcohol ( a sugar or hydroxylic amino acids) with anomeric carbon of a sugar. Example: oligo or polysaccharides. * N- glycoside compounds: they are formed by combination of nitrogen containing bases or amidic amino acids with anomeric carbon of a sugar. Example: nucleosides.

MS/ Reactions/ Glycoside formation O- glycoside N- glycoside

Monosaccharide Derivatives Reducing sugars: sugars with free anomeric carbons - they will reduce oxidizing agents, such as peroxide, ferricyanide and some metals (Cu and Ag) Reducing sugars: sugars with free anomeric carbons - they will reduce oxidizing agents, such as peroxide, ferricyanide and some metals (Cu and Ag) These redox reactions convert the sugar to a sugar acid These redox reactions convert the sugar to a sugar acid Glucose is a reducing sugar - so these reactions are the basis for diagnostic tests for blood sugar Glucose is a reducing sugar - so these reactions are the basis for diagnostic tests for blood sugar

Oligosaccharides Definition: Definition: *They are composed of 2-10 sugars. *They are composed of 2-10 sugars. *Disaccharides are most important oligosaccharides that are found in free form. *Disaccharides are most important oligosaccharides that are found in free form. Example: Maltose, sucrose. Example: Maltose, sucrose. *Oligosaccharides with more than 2 residues usually are found as bound to the other compounds. *Oligosaccharides with more than 2 residues usually are found as bound to the other compounds. Example: glycoproteins or glycolipids. Example: glycoproteins or glycolipids.

DS/ Reactions/ Glycoside formation

DS formed by linkage of simple MS α ( D) glucopyranosyl 1, 2 fructofuranoside β ( D) galactopyranosyl 1 4 glucopyranose

DS/ Classification and nomenclature 1- Reducing disaccharides are formed by combination of anomeric carbon of one sugar with a hydroxyl group of another one. Because of one free anomeric carbon they are reducing. An yle suffix is added to the name of non-reducing residue. 1- Reducing disaccharides are formed by combination of anomeric carbon of one sugar with a hydroxyl group of another one. Because of one free anomeric carbon they are reducing. An yle suffix is added to the name of non-reducing residue. Example: Maltose, lactose. Example: Maltose, lactose. 2-Non-reducing disaccharides are formed by combination of anomeric carbons of two sugars. Because there is no free anomeric carbon they are non-reducing. An yle suffix is added to the name of one and an ide suffix is added to the other one. 2-Non-reducing disaccharides are formed by combination of anomeric carbons of two sugars. Because there is no free anomeric carbon they are non-reducing. An yle suffix is added to the name of one and an ide suffix is added to the other one. Example: Sucrose, Trehalose. Example: Sucrose, Trehalose.