Carbohydrate biochemistry (Part I)

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 Carbohydrates

Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis.

Many, but not all, carbohydrates have the empirical formula (CH₂O)ₙ, [n≥3];  some also contain nitrogen, phosphorus, or sulfur.

Carbohydrate literally means ‘hydrates of carbon’.

Carbohydrates are the most abundant biomolecules on Earth.

Occurrence & Function

Certain carbohydrates (sugar and starch) are a dietary staple and abundant dietary source of energy (4 cal/g) 

Insoluble carbohydrate polymers serve as structural and protective elements:

       in the cell walls of bacteria and plants

       in the connective tissues of animals

       lubricate skeletal joints

       participate in recognition and adhesion between cells

Complex carbohydrate polymers that are covalently attached to proteins or lipids are called glyco-conjugates.

act as signals that determine the intracellular location or metabolic fate of these hybrid molecules

Carbohydrates are precursors of many organic molecules (fats, amino acids, etc.)

They serve as storage form of energy (Ex- Glycogen, Starch)

Classification

The word “saccharide” is derived from the Greek ‘sakcharon’, meaning “sugar”.

Monosaccharides (simple sugars): Consist of a single polyhydroxy aldehyde or ketone unit. Ex- Glucose, Fructose

Glucose

Oligosaccharides: Consist of short chains of monosaccharide units, or residues (2-10), joined by characteristic linkages called glycosidic bonds. Ex- Raffinose

Raffinose

Disaccharides: Consists of  two monosaccharide units joined by glycosidic bond. Ex- Sucrose (Glucose + Fructose)

Sucrose

Polysaccharides: Sugar polymers containing more than 20 or so monosaccharide units, and some have hundreds or thousands of units. Ex- Cellulose, Glycogen

Monosaccharides

Simplest carbohydrates that cannot be hydrolyzed to smaller carbohydrates.

General chemical formula of unmodified monosaccharide is (C.H₂O)ₙ  where n≥3

Consist of a single polyhydroxy aldehyde or ketone unit. 

The most abundant monosaccharide in nature is the six-carbon sugar D-glucose. 

Monosaccharides of more than four carbons tend to have cyclic structures.

Ex- Glyceraldehyde, Glucose, Fructose, etc. 

Classification of monosaccharides

Classified according to 3 different characteristics:

Placement of its carbonyl group

Number of carbon atoms present

Chiral handedness

Classification based on placement of carbonyl group

ALDOSE: Functional group is an aldehyde group (-CHO)

Ex- Glyceraldehyde, Glucose, etc

KETOSE: Functional group is a keto group (>C=O)

Ex- Dihydroxyacetone, Fructose, etc.

Classification based on number of carbon atoms

On the basis of the number of carbon atoms present, monosaccharides can be classified as:

Triose (3 C)

Tetrose (4 C)

Pentose (5 C)

Hexose (6 C)

Heptose (7 C)

Stereoisomers

Stereoisomers: Compounds that have same structural formulae but differ in their spatial configuration. 

A carbon is said to be asymmetric (chiral) when it is attached to four different atoms or groups. 

The number of asymmetric carbon atoms (n) determines the possible number of isomers of a given compound which is equal to 2ⁿ. 

Stereoisomerism is a characteristic feature of all sugars except Dihydroxyacetone. 

Example- 

    Glucose has 4 asymmetric carbon atoms. No. of isomers = 2⁴ = 16

   Glyceraldehyde has 1 asymmetric carbon atom. No. of isomers = 2¹ = 2

   Dihydroxyacetone has no asymmetric carbon atoms. Hence, no isomer is possible.

Classification based on chiral handedness

D and L isomers: Assignment of D or L isomer is made according to the orientation of the asymmetric carbon atom furthest from the carbonyl group.

In a standard Fischer projection if the hydroxyl group is on the right, the molecule is D sugar, and if the hydroxyl group is on the left, the molecule is L sugar. 

D-sugars are biologically more common.

Optical activity of sugars

It is the characteristic feature of compounds with asymmetric carbon atoms. 

When a beam of polarized light is passed through a solution of an optical isomer, it will be rotated to either the right or left. 

The terms dextrorotatory (+) and levorotarory (-) are used to compounds that respectively rotate the plane of polarized light to the right or to the left.

It may be noted that the D and L configurations of sugars are primarily based on the structure, optical activities may be different.

Racemic mixture: If dextrorotatory and levorotatory isomers are present in equal concentration, it is known as racemic mixture or DL mixture. Racemic mixture does not exhibit any optical activity, since the dextro- and levorotatory activities cancel each other.

Epimers

If two monosaccharides differ from each other in their configuration around a single specific carbon (other than anomeric carbon), they are referred to as epimers to each other.

D-glucose and D-mannose differ only in the stereochemistry at C-2, are epimers.

D-glucose and D-galactose which differ at C-4, are epimers.

Inter-conversions of epimers (eg.- glucose to galactose and vice versa) is known as epimerization and is catalyzed by a group of enzymes called epimerases.

Common Monosaccharides Have Cyclic Structures

In aqueous solution, aldotetroses and all monosaccharides with five or more carbon atoms in the backbone occur predominantly as cyclic (ring) structures in which the carbonyl group has formed a covalent bond with the oxygen of a hydroxyl group along the chain. 

The formation of these ring structures is the result of a general reaction between alcohols and aldehydes or ketones to form derivatives called hemiacetals or hemiketals. 

These structures contain an additional asymmetric carbon atom and thus can exist in two stereoisomeric forms.

Hemiacetal formation

Hemiketal formation

D-glucose exists in solution as an intramolecular hemiacetal in which the free hydroxyl group at C-5 has reacted with the aldehydic C-1, rendering the latter carbon asymmetric and producing two stereoisomers, designated  as α and β.

These six-membered ring compounds are called pyranoses because they resemble the six membered ring compound pyran.

The systematic names for the two ring forms of D-glucose are α-D-glucopyranose  and β-D-glucopyranose.

Only aldoses having five or more carbon atoms can form pyranose rings.

Aldohexoses and ketohexoses also exist in cyclic forms having five membered rings, which, because they resemble the five membered ring compound furan, are called furanoses.

The six-membered aldopyranose ring is much more stable than the aldofuranose ring and predominates in aldohexose solutions.

Anomers

Isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or hemiketal carbon atom are called anomers.

The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon.

In case of α-anomer, the –OH group held by anomeric carbon is on the opposite side of the –CH2OH group of the sugar ring. The opposite is true for β-anomers.

The α- and β-anomers of D-glucose interconvert in aqueous solution by a process called mutarotation.

Thus, a solution of α-D-glucose and a solution of β-D-glucose eventually form identical equilibrium mixtures having identical optical properties. This mixture consists of about one-third α-D-glucose (36%), two-thirds β-D-glucose (63%), and very small amounts of the linear and five-membered ring (glucofuranose) forms (1%).

             

 D-glucose      ⃡       Equilibrium mixture        ⃡         β-D-glucose 

   +112.2°                             +52.7°                                  +18.7°

Ketohexoses also occur in α and β anomeric forms.

In these compounds the hydroxyl group at C-5 (or C-6) reacts with the keto group at C-2, forming a furanose (or pyranose) ring containing a hemiketal linkage.

D-Fructose readily forms the furanose ring, the more common anomer of this sugar in combined forms or in derivatives is D-fructofuranose.

The specific optical rotation of fructose is -92° at equilibrium. 

Monosaccharides Are Reducing Agents

Monosaccharides can be oxidized by relatively mild oxidizing agents such as ferric (Fe3+) or cupric (Cu2+).

The carbonyl carbon is oxidized to a carboxyl group.

Sugars capable of reducing ferric or cupric ion are called reducing sugars. They have free aldehyde or ketone group present in their structure.

Ex- Glucose

Sugars not capable of reducing ferric or cupric ion are called non-reducing sugars. They do not have free aldehyde or ketone group present in their structure.

Ex- Sucrose

This property is the basis of Fehling’s reaction, a qualitative test for the presence of reducing sugar.

Monosaccharide derivatives

There are a number of sugar derivatives in which a hydroxyl group in the parent compound is replaced with another substituent, or a carbon atom is oxidized to a carboxyl group.

• In amino sugars, an –NH2 group replaces one of the -OH groups in the parent hexose. 
• Substitution of –H for –OH produces a deoxy sugar.
• The acidic sugars contain a carboxyl group, which confers a negative charge at neutral pH.

Sugar acids: Oxidation of aldehyde or primary alcohol groups in the monosaccharide results in sugar acids.

The acidic sugars contain a carboxyl group, which confers a negative charge at neutral pH.

Examples:

Gluconic acid is produced from glucose by oxidation of aldehyde group.

Glucuronic acid is formed from glucose by oxidation of primary alcohol group (C6).

Amino sugars: When one or more hydroxyl groups of the monosaccharide are replaced by amino groups, the products formed are called amino sugars.

They are present as constituents of heteropolysaccharides.

Examples:

D-glucosamine

D-galactosamine

They are sometimes acetylated.

Example:

N-acetyl-D-glucosamine

Deoxysugars: They contain one oxygen less than that of their parent molecule. 

The groups –CHOH and –CH2OH become –CH2 and –CH3 due to absence of one oxygen atom.

Examples: 

D-2-Deoxyribose

L-Rhamnose

L-Fucose

Sugar alcohols: Sugar alcohols (polyols) are produced by reduction of aldoses or ketoses.

Examples: 

Sorbitol from glucose

Mannitol from mannose

Alditols: The monosaccharides on reduction yield polyhydroxy alcohols known as alditols.

Examples:

Ribitol (constituent of flavin coenzymes)

Glycerol (Component of lipid)

Xylitol (Sweetener used in sugarless gums and candies)