Sugars & Polysaccharides

1. Learning Outcomes

After studying this module, you shall be able to:

• Understand the general definition and classification of carbohydrates.

• Describe straight-chain and cyclic structures of carbohydrates.

• Analyze the chemical properties of monosaccharides and their derivatives.

• Identify types of disaccharides and their properties.

• Characterize polysaccharides and their types.

• Explain the function of carbohydrates.

2. Introduction

Carbohydrates are a significant class of naturally occurring organic compounds found in plants, created through the process of photosynthesis. The term "carbohydrate" derives from the general formula $C_n(H_2O)_n$, which strictly applies to monosaccharides. Other carbohydrates, such as oligosaccharides and polysaccharides, are essentially constructed from monosaccharide units but have slightly different general formulas. The term "saccharides" originates from Greek, meaning sugar.

Common examples of polysaccharides include glycogen in animals and both starch and cellulose in plants.

2.1 Definition of Carbohydrates

Carbohydrates are polyfunctional compounds characterized by the presence of the following functional groups:

1. Alcoholic hydroxy group, -OH

2. Aldehyde group, -CHO

3. Ketone group, >C=O

A precise definition of carbohydrates can be stated as: polyhydroxy aldehydes or polyhydroxy ketones, and large molecules that yield these compounds upon hydrolysis. However, this definition does not account for certain carbohydrates lacking a free carbonyl group, necessitating an improved definition:

Improved Definition: A polyhydroxy compound that has an aldehyde or a ketone function present, either free or as a hemiacetal or acetal.

3. Classification of Carbohydrates

Carbohydrates can be categorized based on different criteria:

3.1 Based on Number of Simple Sugars

Carbohydrates are divided into three classes:

1. Monosaccharides (Simple Sugars): Consist of a single sugar unit that cannot be hydrolyzed into simpler sugars (e.g., glucose and fructose).

2. Oligosaccharides: Comprises 2 to 10 units of monosaccharides. Oligosaccharides composed of two monosaccharides are known as disaccharides, whereas those with three are referred to as trisaccharides. For example, sucrose, with the formula $C_{12}H_{22}O_{11}$, is a disaccharide because hydrolysis yields one molecule of glucose and one molecule of fructose.

3. Polysaccharides: Contain more than ten monosaccharide units in their structure. Hydrolysis of starch or cellulose provides a large number of glucose units.

3.2 Further Classification of Monosaccharides

3.2.1 Based on Carbonyl Function

Monosaccharides can be divided based on the presence of either an aldehyde or a ketone:

• Aldoses: Contain the aldehyde function (-CHO).

• Ketoses: Contain the keto group (>C=O).

3.3 Based on Number of Carbon Atoms

Monosaccharides are further classified as follows based on the number of carbon atoms present:

• Trioses: 3 carbon atoms

• Tetroses: 4 carbon atoms

• Pentoses: 5 carbon atoms

• Hexoses: 6 carbon atoms
  For instance, glucose is a six-carbon aldose (aldohexose), while fructose is a six-carbon ketose (ketohexose).

4. Structure and Stereochemistry of Monosaccharides

4.1 Enantiomers, Diastereomers, and Epimers (Isomers)

Monosaccharides, the fundamental building blocks of carbohydrates, can exist as either aldoses or ketoses. Glyceraldehyde, the simplest aldose, exemplifies this with only one asymmetric carbon atom or chiral center (C-2). The two possible configurations of the hydroxyl (OH) and hydrogen (H) on the CH2OH group yield:

• L-isomer: OH group projects left.

• D-isomer: OH group projects right.

These two stereoisomers are enantiomers, mirror images of one another.

4.1.2 Diastereomers

In carbohydrates with multiple asymmetric carbon atoms, the configuration of D or L is based solely on the highest-numbered asymmetric carbon. For instance, aldotetroses possess two chiral centers, leading to the possibility of four stereoisomers, including D-erythrose and D-threose. These are diastereomers because they differ in configuration at one chiral center while remaining non-superimposable.

4.1.3 Epimers

Diastereomers that differ in configuration at just one asymmetric carbon are termed epimers. Glucose and galactose are classic examples of epimers.

4.1.4 Commonality of D-sugars

It should be noted that D-sugars predominate naturally, particularly in food sources where five or six carbon atoms are common.

5. Cyclic Structures of Sugars

5.1 Anomers, Racemic Mixture, Mutarotation

The formation of cyclic structures occurs when an aldehyde and alcohol react to create a hemiacetal, resulting in the formation of five- or six-membered ring structures. This reaction introduces a new chiral center at carbon 1, significantly increasing the number of possible isomers. The cyclic forms of glucose can exist as:

• α-anomer: Hydroxyl group (OH) on the same side as the oxygen bridge.

• β-anomer: Hydroxyl group on the opposite side of the oxygen bridge.

5.2 Specific Optical Rotation

The optical rotation for these two configurations differs:

• α-D-glucose: Specific rotation of +113°.

• β-D-glucose: Specific rotation of +19.7°.

An equilibrium mixture of these forms in solution has a specific rotation of +52.5°, with approximately 36% in the α-form and 64% in the β-form.

5.3 Mutarotation

Mutarotation is the process of interconversion between the α and β forms leading to an equilibrium mixture. It is crucial in enzyme assays to allow equilibrium to be achieved between standard and test solutions.

6. Chemical Properties of Monosaccharides

6.1 Action of Acids and Alkalis

6.1.1 Action of Acids

Heating sugars with mineral acids such as H2SO4 leads to the formation of furfural derivatives, which can condense with compounds like α-naphthol to produce colored complexes. This forms the basis for several tests:

• Molisch’s test

• Seliwanoff’s test

• Bial's test

• Tollen’s-phloroglucinol-HCl test

6.1.2 Action of Alkalis

Aldoses and ketoses treated with dilute alkalis convert into enediols, which act as strong reducing agents applicable in Benedict’s and Fehling's tests.

6.2 Oxidation and Reduction of Sugars

6.2.1 Oxidation of Sugars

Under specific conditions, aldoses can be oxidized to form:

• Aldonic acids (e.g., glucose to gluconic acid).

• Saccharic acids.

• Uronic acids.

The oxidation of aldoses with hypobromous acid results in aldonic acid formation. Nitric acid oxidation leads to conversion of both the aldehyde and terminal primary alcohol groups into carboxyl groups.

6.2.2 Reduction of Sugars

Aldoses and ketoses can be reduced to form polyhydroxy alcohols called alditols, with mannitol and sorbitol being common examples. In the cyclic form, aldoses produce isomers called iso-lactones.

6.3 Osazone Formation

Osazones are yellow or orange crystalline derivatives formed when reducing sugars react with phenylhydrazine. Osazones from glucose, mannose, and fructose appear identical due to the similarity in their lower four carbon atoms. Their osazone crystals differ in form:

• Glucosazone: needle-shaped

• Lactosazone: powder-puff shaped

• Maltosazone: sunflower-shaped

Non-reducing sugars lack a free carbonyl group and cannot form osazones, as observed with sucrose.

6.4 Glycoside Formation

Glycosides arise when the hydroxyl group of an anomeric carbon reacts with OH or NH groups of another molecule. These bonds are called glycosidic or glycosyl bonds, crucial in forming disaccharides, oligosaccharides, and polysaccharides.

• O-glycosides: Sugar bonded to oxygen.

• N-glycosides: Sugar bonded to nitrogen.

7. Derivatives of Monosaccharides

Key derivatives include:

• Phosphoric acid esters of monosaccharides (e.g., glucose-1-phosphate).

• Amino sugars (e.g., glucosamine).

• Deoxy sugars (e.g., 2-deoxyribose).

• Sugar acids (e.g., ascorbic acid).

• Sugar alcohols.

• Neuraminic acid and sialic acid.

7.1 Phosphoric Acid Esters

These arise from the reaction of phosphoric acid with hydroxyl groups in sugars. This is vital for retaining sugars within cells and is significant for nucleic acids.

7.2 Amino Sugars

Amino sugars replace a hydroxyl group with an amino group (e.g., glucosamine) and play a role in glycolipids and glycoproteins, including drugs like erythromycin.

7.3 Deoxy Sugars

Deoxy sugars replace a hydroxyl group with hydrogen (e.g., 2-deoxyribose in DNA).

7.4 Sugar Acids

Produced through oxidation, significant examples being ascorbic acid and glucuronic acid, the latter being crucial for detoxification.

7.5 Sugar Alcohols

Not very metabolically active but utilized as sweeteners for diabetics (e.g., sorbitol, xylitol).

7.6 Neuraminic Acid

This nine-carbon sugar derives from mannosamine and pyruvate, and serves structural roles in cells.

7.7 Sialic Acid

Sialic acids are acetylated derivatives of neuraminic acid, important in glycoproteins and glycolipids.

8. Disaccharides

Disaccharides comprise two monosaccharide units, characterized by being crystalline, water-soluble, and sweet. They are classified based on the presence of reducing groups:

8.1 Reducing Disaccharides

8.1.1 Maltose

Maltose consists of two glucose units linked by an α(1→4) glycosidic bond, where one anomeric carbon remains free to act as a reducing agent, rendering maltose a reducing sugar. It forms during starch digestion by α-amylase.

8.1.2 Isomaltose

Isomaltose consists of two glucose molecules linked by an α(1→6) glycosidic bond and derived from starch or glycogen's digestion.

8.1.3 Lactose (Milk Sugar)

Lactose comprises one unit of β-galactose and one unit of β-glucose linked via a β(1→4) glycosidic bond. It is a reducing disaccharide hydrolyzed by the lactase enzyme into glucose and galactose.

8.2 Non-Reducing Disaccharides

8.2.1 Sucrose (Common Table Sugar)

Sucrose, a disaccharide of glucose and fructose, contains no free anomeric carbon. It is produced during photosynthesis by plants and can be hydrolyzed into glucose and fructose by the enzyme sucrase (invertase).

9. Polysaccharides

Polysaccharides contain ten or more monosaccharide units or their derivatives, characterized by colloidal sizes, and are linked by glycosidic bonds. Two main categories include:

9.1 Homopolysaccharides (Homoglycans)

Starch

The storage form of glucose in plants exists in two forms:

• Amylose: A linear polymer of D-glucose units joined by α(1→4) glycosidic linkages.

• Amylopectin: Similar to amylose, but has branched structures joined by both α(1→4) and α(1→6) linkages.

Glycogen (Animal Starch)

Glycogen serves as the major carbohydrate storage form in animals, particularly in the liver and muscle. It has a high degree of branching, connecting every 8-10 glucose units via α(1→6) links and consists of a core protein called glycogenin. The functions of muscle glycogen focus on providing glucose for energy and liver glycogen on maintaining blood glucose levels.

9.2 Cellulose

Cellulose is composed of long, linear chains of glucose linked by β(1→4) glycosidic linkages, making it indigestible to humans. However, it is nutritionally significant as dietary fiber, reducing the incidence of diseases such as cardiovascular disease and colon cancer.

9.3 Inulin

Inulin comprises D-fructose polymers linked by β(1→2) glycosidic bonds, present in tubers of specific plants like chicory. It is undigested by human enzymes, but serves clinical importance for studying kidney filtration rates.

9.1 Heteropolysaccharides (Heteroglycans)

Glycosaminoglycans (GAGs)

GAGs are unbranched heteropolysaccharides composed of repeating disaccharides that comprise amino sugars and uronic acids. These large carbohydrate chains are integral to the extracellular matrix and significantly contribute to cushioning mechanical shocks, lubrication, and cellular regulation. Types of GAGs include:

• Hyaluronic acid

• Chondroitin sulfate

• Keratan sulfate

• Dermatan sulfate

• Heparin

• Heparan sulfate

10. Glycoproteins

Glycoproteins consist of proteins with covalently attached oligosaccharides. They contain shorter carbohydrate chains than proteoglycans (less than 4% carbohydrate). Functions include:

• Important reproductive hormones

• Most human plasma proteins

• Integral membrane proteins

• Secreted proteins (e.g., antibodies, hormones).

11. Functions of Carbohydrates

Carbohydrates serve multiple crucial functions including:

• Energy source (e.g., glucose)

• Energy storage (e.g., glycogen in animals, starch in plants)

• Structural components (e.g., glycosaminoglycans, cellulose)

• Dietary fibers from non-digestible carbohydrates like cellulose

• Constituents of nucleic acids (ribose and deoxyribose)

• Involvement in detoxification processes (e.g., glucuronic acids).

12. Summary

Carbohydrates are polyhydroxy aldehydes and ketones. The classification includes:

• Aldoses and ketoses based on carbonyl groups.

• Disaccharides, oligosaccharides, and polysaccharides form through glycosidic linkages.

• Reducing sugars are those containing free oxidizable anomeric carbons.

• Isomers categorized as epimers differ at one asymmetric carbon.

• Enantiomers are mirror images designated as D and L sugars.

• Disaccharides involve two monosaccharides linked glycosidically (e.g., lactose, sucrose).

• Polysaccharides (glycans) comprise many monosaccharide derivatives linked glycosidically (e.g., glycogen, starch, cellulose).

• Proteoglycans and glycosaminoglycans contain sugar derivatives essential for structural integrity, while glycoproteins involve carbohydrate chains bound to proteins, significant for various biological functions.