Monosaccharides

General characteristics of Carbohydrates The term carbohydrate is derived from the French term : hydrate de

carbone

Compounds composed of C, H, and O

Empirical formula (CH2O)n when n = 5 then C5H10O5

Not all carbohydrates have this empirical formula: e.g. deoxysugars,

amino sugars etc

Carbohydrates are the most abundant compounds found in nature

(cellulose: 100 billion tons annually)

General characteristics -They have large number of hydroxyl groups (polyhydroxy)

-In addition they may contain-an aldehyde group (polyhydroxyaldehydes) or a keto group-(polyhydroxyketones).

-Their derivatives may also contain nitrogen, phosphorus or sulfur.

OHCH

R

OCH

R

OC

HYDROXYL GROUPKETO GROUP

ALDEHYDE GROUP

1) Sources of energy, especially for brain cells and Red blood cells.

2) Intermediates in the biosynthesis of other basic biochemical entities (fats and proteins)

3) Associated with other entities such as glycosides, vitamins and antibiotics)

4) Form structural tissues in plants and in microorganisms

5) Participate in biological transport, cell-cell recognition,

activation of growth factors, modulation of the immune system

Functions of Carbohydrates

1) Monosaccharides (monoses or glycoses)Trioses, Tetroses, Pentoses, Hexoses

2) OligosaccharidesDi, tri, tetra, penta, up to 9 or 10

Most important are the disaccharides

3) Polysaccharides or glycansa)Homopolysaccharides

b) Heteropolysaccharides

Classification of carbohydrates

-Also known as simple sugars

-Classified either by the number of carbon atoms or by the nature of functional group-aldoses or ketoses

-Most of the carbohydrates (99%) are straight chain compounds

-D-glyceraldehyde is the simplest of the aldoses (aldotriose)

-All other sugars have the ending ose (glucose, galactose, ribose, lactose, etc…)

Monosaccharides

1-According to number of carbons they contain in their backbone structures-

It is a variable prefix followed by the suffix(-ose) (Trioses=3C), (Tetroses=4C), (Pentoses=5C),

(Hexoses=6C),(Heptoses=7C).

2- According to nature of reactive group - Aldose sugars e.g. glyceraldehyde or a ketose sugars

e.g.dihydroxyacetone depending on the presence of Aldehyde or keto group.

MONOSACCHARIDES NOMENCLATURE

D-Glyceraldehyde

OHCH

OC

OHCH

2

2

Dihydroxyacetone.

C

Monosaccharides ClassificationName Relevant examples

3 Triose Glyceraldehyde, Dihydroxyacetone

4 Tetrose

Erythrose ,Erythrulose

5 Pentose

Ribose, Ribulose, Xylulose

6 Hexose Glucose, Galactose, Mannose, Fructose

9 NonoseNeuraminic acidalso called Sialic acid

Aldose sugars

n - denotes the number of asymmetric carbon atoms

Ketose sugars

n - denotes the number of asymmetric carbon atoms

-It Is the carbon atom that is attached to 4 different groups.

-All monosaccharides have it except dihydroxyacetone.

-Different isomers are possible based on the presence of number of asymmetric carbon atoms

Asymmetric carbon atom

OHCH

OC

OHCH

2

2

Dihydroxyacetone.

1) D and L isomerism- The designation of a sugar isomer as the D form or

of its mirror image as the L form is determined by comparison of its

spatial relationship to the parent compound of the carbohydrates, the

three-carbon sugar glycerose (glyceraldehyde), also called reference

sugar.

The orientation of the —H and —OH groups around the carbon atom

adjacent to the terminal primary alcohol carbon ( as carbon 5 in glucose)

determines whether the sugar belongs to the D or L series.

When –OH is on the right side the sugar is D isomer; when it is on the

left, it is the L isomer.

Isomerism in Monosaccharides

D-Glyceraldehyde L-Glyceraldehyde

D and L Isomers Of Glyceraldehyde

1) Most of the monosaccharides occurring in mammals are D sugars, and the enzymes responsible for their metabolism are specific for this

configuration.

2) Simple monosaccharides with four, five, six, and seven carbon atoms have multiple asymmetric carbons, they exist as diastereoisomers,

isomers that are not mirror images of each other.

Some sugars naturally occur in the L form e.g.L-Arabinose and L-Fucose are found in glycoproteins, while L- Xylulose is produced

during the metabolism of Glucose in Uronic acid pathway. It is subsequently converted to its D form.

Isomers of Monosaccharides(D and L)

D and L Isomers of Fructose

2) Optical Isomerism-

The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized light is passed through a

solution of an optical isomer, it rotates either to the right, dextrorotatory (+), or to the left, levorotatory (–). The direction of rotation of polarized light is independent of the stereochemistry of the sugar, so it may be designated

D(–), D(+), L(–), or L(+). For example, the naturally occurring form of fructose is the D(–) isomer. In solution, glucose is dextrorotatory, and glucose solutions

are sometimes known as dextrose.

Isomerism in Monosaccharides

Measurement of optical activity in chiral or asymmetric molecules using plane polarized light is called Polarimetry. The measurement of optical

activity is done by an instrument called Polarimeter.

POLARIMETRY

D-Glucose +52.7D-Fructose -92.4

D-Galactose +80.2L-Arabinose+104.5D-Mannose +14.2D-Xylose +18.8Lactose +55.4Sucrose +66.5Maltose +130.4

Invert sugar -19.8Dextrin +195

Specific rotation of various carbohydrates at 20oC

3) Epimers- Epimer carbons are the middle asymmetric carbons other than the sub terminal one (related to D&L

forms ).The differences in orientation of –OH group around only one of these epimer carbons will produce epimers.

Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose are known as epimers.

Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2 and 4, respectively.

Mannose and Galactose are not epimers of each other as they differ in configuration around 2 carbon atoms.

Isomers of Monosaccharides

Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose

are known as epimers. Biologically, the most important epimers of glucose are mannose and galactose, formed by

epimerization at carbons 2 and 4, respectively. Mannose and Galactose are not epimers of each other as they differ in

configuration around 2 carbon atoms.

Epimers of Glucose

Isomers of Monosaccharides(Aldoses)

OHCH

OC

OHCH

2

2

Isomers of Monosaccharides (Ketoses)

OHCH

OC

OHCH

2

2

4) Pyranose and furanose ring structures-

The ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a

five-membered ring)For Glucose in solution, more than 99% is in the Pyranose form

Isomers of monosaccharides

5) Anomers-The ring structure of an aldose is a hemiacetal, since it is

formed by combination of an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a

hemiketal. The ring can open and reclose allowing the rotation to occur around the carbon bearing the reactive carbonyl group yielding two possible configurations- α and β of the hemiacetal and hemiketal. The carbon about which this rotation occurs is called Anomeric

carbon and the two stereoisomers are called Anomers. Crystalline glucose is α-D-glucopyranose.

Isomers of monosaccharides

Cyclic Fischer Projectionof -D-Glucose

Anomers

Haworth Projectionof -D-Glucose

When drawn in the Haworth projection, the α configuration places the hydroxyl downward. While the β is the reverse.

Anomers

When drawn in the Fischer projection, the configuration places the hydroxyl attached to the anomeric carbon to the right of the ring, While the

is the reverse

Anomers

Carbohydrates can change spontaneously between the and configurations through the formation of intermediate open chain. This will lead to a process known as mutarotation. It is the gradual change of

specific optical rotation of sugar.In solution

Mutarotation

6) Aldose-ketose isomerismFructose has the same molecular formula as glucose but differs in its

structural formula, there is a potential keto group at position 2 (the anomeric carbon of

fructose), whereas there is a potential aldehyde group at position 1, the anomeric carbon

of glucose.

Glucose and Fructose are Aldose ketose isomers

Isomers of Monosaccharides

1) Fischer projection: straight chain representation

2) Haworth projection: simple ring in perspectiveConformational representation:

3) Chair and boat conformations

Structural representation of sugars

1) Draw either a six or 5-membered ring including oxygen as one atom.

2) Most aldohexoses are six-memberedaldotetroses, aldopentoses, ketohexoses are 5-

membered

Rules for drawing Haworth projections

Number the ring clockwise starting next to the oxygen

if the substituent is to the right in the Fischer projection, it will be drawn down in the Haworth

projection (Down-Right Rule)

Rules for drawing Haworth projections

In Haworth configuration all groups to the right of carbon backbone in Fischer projection are oriented

down while all groups to the left of carbon backbone are oriented up, except those around

C5,the reverse orientation occurs.

Rules for drawing Haworth projections

When drawn in the Haworth projection, the α configuration places the hydroxyl downward. While

the β is the reverse.

Rules for drawing Haworth projections

Pyranose and Furanose forms of Glucose

Pyranose and Furanose forms of Ribose

Chair and Boat Conformations

Chair and boat conformations of a pyranose sugar

2 possible chair conformations of -D-glucose

1)Osazone formation

2) Reduction

3) Oxidation

4) Action of alkali

5) Action of acid

6)Glycoside formation

7)Ester formation

Reactions of monosaccharides

-Used for the identification of sugars

-Consists of reacting the monosaccharide with phenyl hydrazine

-A crystalline compound with a sharp melting point and a characteristic shape is obtained

D-fructose and D-mannose give the same needle shaped osazone crsytals as D-glucose

-Seldom used these days for identification

-HPLC or mass spectrometry is used now a days for the

identification of sugars

Formation of osazones

Formation of osazones

Aldoses may be oxidized to 3 types of acids1) Aldonic acids: aldehyde group is converted to a carboxyl group Glucose – Gluconic acid, Galactose-Galactonic acid

and Mannose- Mannonic acid

2) Uronic acids: aldehyde is left intact and primary alcohol at the other end is oxidized to COOH

Glucose --- Glucuronic acidGalactose --- Galacturonic acidMannose-----Mannuronic acid

3) Saccharic acids: (glycaric acids) – oxidation at both ends of monosaccharide)

Glucose ---- Gluco saccharic acidGalactose --- Mucic acid

Mannose --- Mannaric acid

Oxidation reactions

Oxidation Products Of D-Glucose

-Either done catalytically (hydrogen and a catalyst) or enzymatically

-The resultant product is a polyol or sugar alcohol -Glucose forms sorbitol (glucitol)

-Mannose forms mannitol

-Fructose forms a mixture of mannitol and sorbitol

-Glyceraldehyde forms glycerol

Reduction

Sructures of some sugar alcohols

-Monosaccharides are normally stable to dilute acids, but are dehydrated by strong acids

-D-ribose when heated with concentrated HCl yields furfural

-D-glucose under the same conditions yields 5-hydroxymethyl furfural

- Forms the basis of Molisch test, Seliwanoff test and Bial’s Test

Action of strong acids on monosaccharides

-In mild alkaline conditions Enediols are formed

- Enediols are highly reactive sugars and are powerful reducing agents.

-This allows the interconversion of D-mannose, D-fructose and D-glucose

-This interconversion reaction is known as Lobry de Bruyn- Van Eckenstein transformation.

- Strong alkalis cause CARAMELISATION (Decomposition)of sugars.

Action of Alkalies on sugars

-Enediols obtained by the action of bases are quite susceptible to oxidation when heated in the

presence of an oxidising agent. It forms the basis of Benedict’s and Fehling test for the detection of

reducing sugars-Copper sulfate is frequently used as the oxidising

agent and a red precipitate of Cu2O is obtained-Sugars which give this reaction are known as

reducing sugarsFehling’s solution : KOH or NaOH and CuSO4

Benedict’s solution: Na2CO3 and CuSO4

Action of Alkalies on sugars

1-Amino sugarsThey are formed by replacing the hydroxyl group

(at C2 usually) of monosaccharides by amino group. The most common amino sugars are

glucosamine and galactosamine.-Glucosamine is present in Heparin, Hyaluronic

acid and blood group substances. -Galactosamine is present in Chondroitin of

cartilages and tendons.

Important derivatives of monosaccharides

-The amino group may be condensed with active acetate forming N-acetyl glucosamine.

-They are components of glycosaminoglycans and some glycosphingolipids (lipids).

-N-acetyl Mannosamine- it is a component of glycoproteins and gangliosides(Lipids) of cell membrane.

- A polymer of N-Acetyl Glucosamine is a component of chitin- N-Acetyl Galactosamine is a component of Chondroitin sulphate.

Amino Sugars

Amino sugar acids are produced by condensation of amino sugar with Pyruvic or lactic acid.

e.g.Muramic acid is produced by the condensation of lactic acid with D- Glucosamine. Certain bacterial cell walls contain Muramic acid.

N-Acetyl Neuraminic acid is formed from the condensation of Pyruvic acid with N-Acetyl

Mannosamine.

Amino Sugar acids

-Are formed by removal of an oxygen atom usually from

2 nd carbon atom

-one quite ubiquitous deoxy sugar is 2’-deoxy ribose which is the sugar found in DNA

-6-deoxy-L-mannose (L-rhamnose) is used as a fermentative reagent in bacteriology

2-Deoxy sugars

Deoxy Sugars

Sugar acids-Are formed by the oxidation of aldehyde

C1(Aldonic acid) -or terminal hydroxyl group at C6 of aldose

sugar(uronic acid) -or both (saccharic) to form carboxylic group.

-Glucuronic and Iduronic acids are the components of glycosaminoglycans.

-L-ascorbic acid(vitamin C) is a sugar acid. -Glucuronic acid is involved in detoxification of

bilirubin and other foreign compounds.

3-Sugar acids

Are formed by the reduction of the carbonyl group (aldehyde or ketone ) of monosaccharide

4-Sugar alcohols

- Hydroxyl groups of sugars can be esterified to form Acetates, phosphates, benzoates etc.

-Sugars are phosphorylated at terminal C1 hydroxyl group or at other places .At terminal hydroxyl: Glucose-6-P or ribose-5-P.At C1 hydroxyl group: Glucose-1-P .At both places: Fructose 2,6

bisphosphate - Metabolism of sugars inside the cells starts with

phosphorylation.-Sugar phosphates are also components of nucleosides and

nucleotides.

5-Sugar Esters

They are formed by the reaction of the hydroxyl group of anomeric carbon (hemiacetal or

hemiketal) with the hydroxyl group of any other molecule with the elimination of water. A

glycosidic bond is formed. 2nd molecule may be:

Another sugar(glycon)disaccharide - polysaccharide.

A non carbohydrate moiety (aglycon) as Methanol, glycerol, sterols .etc.

6-Glycosides

Condensation reactions: Acetal and Ketal formation

1) Cardiac Glycosides- These include derivatives of digitalis and strophanthus such as oubain.

2)Streptomycin is used as an antibiotic

3) Phloridzine -displaces Na+ from the binding site of “carrier protein” and prevents the binding of sugar

molecule and produces Glycosuria.

Significance of Glycosides