Biomolecules of the Cell - Carbohydrates (Part 2)

In the previous post, we have completed the introduction of carbohydrates and the characteristics of monosaccharides. In this post, we will discuss about characteristics of disaccharides, oligosaccharides and some polysaccharides. 

Let us first understand the disaccharides.

A. Disaccharides:

Disaccharides are formed by the condensation reaction (or dehydration reaction) of two monosaccharide units and water is the by-product of this reaction (as can be seen in the adjacent figure). The covalent linkage that is formed between two monosaccharides is called O-glycosidic bond and it represents the formation of an hemiacetal from an aldehyde and an alcohol. Similarly, a hemiketal is formed from a ketone and an alcohol.

In the adjacent figure (right side), is the disaccharide, maltose, the linkage is α(1-4) linkage. We can see the hemiacetal and acetal ends in the figure.

Types of Disaccharides (Sugars):
a. Reducing and Non-reducing Sugars:

The disaccharides are classified as reducing disaccharide (or sugar) and non-reducing disaccharide (or sugar). The disaccharides that have hemiacetals, are grouped under reducing sugar. Hemiacetals contain a free aldehyde group which can be oxidized into carboxylic acids (or diverse products). Thus, these types of sugars are reducing in nature, hence, they are called reducing sugars.

Another type is non-reducing sugars (disaccharides). Here, the sugar or the disaccharide in an acetal or ketal which cannot be oxidized readily and neither monosaccharide has a free hemiacetal unit. This is so, because both of its anomeric carbon atoms are involved in glycosidic linkage.

In the figure, the glucose on the right is designated as the reducing end of the disaccharide molecule as it can participate in a reduction reaction. In contrast, the glucose on the left represents the non-reducing end as the C-1 carbon atom is the part of the  α(1-4) linkage and it cannot form the open chain. Thus, as maltose contains one reducing end, it is called, reducing sugar. 

b. Properties of Disaccharides: 

The glycosidic bond can be formed between the hydroxyl groups on its component monosaccharide. So, even if both monosaccharides (forming a disaccharide) are the same (e.g., glucose), different bond combinations which is regiochemistry and stereochemistry (like alpha- or beta-) result in disaccharides that are isomers of each other. These are diastereoisomers with different chemical and physical properties.
For example, both maltose and cellobiose are the disaccharides of glucose monomers. However, maltose is the disaccharide with α(1-4) linkage between C1 hydroxyl of one glucose and C4 hydroxyl of another glucose. The configuration is 'α' because the O at the anomeric carbon atom points down from the ring. On the other hand, cellobiose, is the disaccharide with β(1-4) linkage but here, the configuration is β as O points up from the ring. (This β glycosidic linkage is generally depicted by a zig-zag line; however, one glucose molecule is actually flipped over relative to the other).

c. Nomenclature:

As per the standard conventions, the disaccharide is named such that first listing is that of non-reducing monosaccharide on the left followed by glycosidic linkage between the two monosaccharides and then the monosaccharide on the right. For example, with this nomenclature, maltose can be described as Glc(α1-4)Glc (where Glc stands for glucose).
Here is the table of some common reducing and non-reducing disaccharides with their glycosidic linkages.

Reducing Disaccharides
Disaccharide	Unit 1	Unit 2	Bond/Linkage
Cellobiose	Glucose	Glucose	β(1-4)
Gentiobiose	Glucose	Glucose	β(1-6)
Isomaltose	Glucose	Glucose	α(1-6)
Lactose	Galactose	Glucose	β(1-4)
Maltose	Glucose	Glucose	α(1-4)
Mannobiose	Mannose	Mannose	Either α(1-2) α(1-3), α(1-4) or α(1-6)
Xylobiose	Xylopyranose	Xylopyranose	β(1-4)
Non-reducing Disaccharides
Sucrose	Glucose	Fructose	α(1-2)β
Trehalose	Glucose	Glucose	α(1-1)α

B. Oligosaccharides:
Most of the oligosaccharides are not found as isolated molecules. Instead, they may be attached to other biomolecules like proteins or lipids, generally referred to as glycoconjugates. For example, the blood group serotypes (A, B, AB and O) are the result of various oligosaccharides involved in cellular recognition. The lipids on the surface of the erythrocytes are conjugated with various oligosaccharides.

C. Polysaccharides:

Polysaccharides are long chains of monosaccharides joined together by glycosidic bonds (linkages). As mentioned in previous post, polysaccharides maybe branched or unbranched. When all the monosaccharides in a polysaccharide are of the same type, the polysaccharide is called a homopolysaccharide or homoglycan, but when more than one type of monosaccharide is present, then they are called heteropolysaccharides or heteroglycans.

Here, we are going to see about some polysaccharides:

a. Cellulose: It is the most abundant (structural) polysaccharide on the earth. It is a straight chain homopolymer consisting of thousands of glucose moieties attached together by β(1-4) glycosidic linkage present in plants. It is a polymer of cellobiose units (repeats of Glcβ(1-4)Glc) as can be seen in the figure. Humans and many other animals lack the enzyme cellulose which is required to hydrolyze β-glycosidic linkages.
Many hydroxyl groups on the glucose molecules from one chain form hydrogen bonds with the oxygen atoms on the same or neighboring chain thereby holding the chains firmly together side-by side forming microfibrils giving high tensile strength.

b. Chitin: Chitin is to animal kingdom what cellulose is to plant kingdom. It is another abundant linear polysaccharide that forms the structural components of many invertebrates exoskeletons of insects and crustaceans. It is a polymer of units of N-acetyl glucosamine (abbreviated as NAG or GlcNAc) which is linked by β(1-4) glycosidic bond. The only difference between the structure of glucose and N-acetyl-glucosamine is the replacement of the C-2 hydroxyl group with that of an acetylated amino group. This allows for increased hydrogen bonding between adjacent polymers giving chitin more strength than cellulose.

c. Starch: Starch is the homopolymer in which the glucose units are linked via alpha linkages. It is made up of amylose (15-20%) and amylopectin (80-85%). Amylose is a linear polysaccharide linked by α(1-4) linkages while amylopectin is a branched polysaccharide connected by α(1-4) and α(1-6) linkages. The linear linkage is α(1-4) while the branched linkage is α(1-6) between glucose residues which greatly increases the number of free ends in the homopolymeric molecule. The branch points occur in chain after every 20-30 residues. Being the alpha linkages, these can easily be hydrolyzed by alpha amylase which cleaves α(1-4) glycosidic bonds.

d. Glycogen: What starch is to plants, glycogen is to animals and human. The structure is similar to amylopectin meaning the linear, glucose molecules are linked together by α(1-4) glycosidic bond and the branches are linked to these linear chains branching off from α(1-6) glycosidic bond between first glucose of new branch and a glucose on the stem branch.

There are certain differences between starch (amylopectin, more specifically) and glycogen. One of them is that of branching. In glycogen, the branching occurs more frequently  i.e.; branch point is after every 6-10 residues.
The glucose units can be added or removed only from the non-reducing ends of amylopectin and glycogen. The more branch points, the more ends are available for glucose retrieval and storage. Another difference is between the macromolecular structures of both. Amylopectin contains one free glucose at the reducing end of the 'tree branch' whereas glycogen lacks a free reducing end. This is because the glucose residue at the center of the glycogen 'spiral' is covalently linked to a protein called glycogenin (see adjacent figure).

e. Heparin: Heparin is a polysaccharide that is heteropolysaccharide with anti-clotting properties. It has medicinal value for surgery and is used to treat thrombosis. Heparin is found in arterial walls where it facilitates interactions between antithrombin (an inhibitor of blood coagulation) and thrombin (a clot-forming protein).

Biomolecules of the Cell - Carbohydrates (Part 1)

Carbohydrates are the most abundant biomolecules belonging to the class of the organic compounds consisting of carbon (C), hydrogen (H) and oxygen (O). The term 'carbohydrate' generated from 'carbon' and 'hydrate' though some also have nitrogen, phosphorous or sulphur. If you want to define carbohydrate, then the definition goes like this - ‘Carbohydrates are polyhydroxylated aldehydes or ketones.’ They generally have as many Os as Cs (meaning they are highly oxidised). The general formula depicting the carbohydrate is (CH2O)n  where ‘n’ is the number of carbon atoms.
From where do these carbohydrates originate? Yes, one of the origins is - the product of photosynthesis (sucrose) which is a reductive condensation of carbon dioxide and water in the presence of light and the chlorophyll pigment.

Classification of Carbohydrates:

Carbohydrates are called ‘saccharides’ or sugars. The carbohydrates can be broadly divided into the following groups depending on the number of carbon atoms:

1. Monosaccharides: It is the simplest and smallest unit of carbohydrate containing 3-7 carbon atoms. The one with three carbon atoms are called trioses (ex. glyceraldehyde); the one with four carbon atoms are tetroses (ex. erythrose); the one with five carbon atoms are pentoses (ex. ribose), the one with six carbon atoms are hexoses (ex. glucose shown in figure) and the one with seven carbon atoms are heptoses (ex. sedoheptulose). These are the very basic carbohydrates from which the below described disaccharides, oligosaccharides and polysaccharides are formed.

2. Disaccharides:  A disaccharide consists of two monosaccharides joined together by a glycosidic linkage. Disaccharides can be homo (consisting of two same monomers; ex. mannose which consists of two glucose molecules) or hetero-disaccharide (consisting of two different monomers; ex. lactose which consists of  galactose + glucose as depicted in the adjacent figure).

3. Oligosaccharides: An oligosaccharide contains upto 10 monosaccharide units joined by a glycosidic linkage. They are generally found linked to amino acid chains in proteins or lipid moieties. 

4. Polysaccharides: They are the complex sugars; polymers consisting of many monosaccharide units joined together by glycosidic linkages. They are very large, maybe branched or unbranched biomolecules. Polysaccharides can be homo-polysaccharides as well as hetero-polysaccharides wherein, in the former, all the monosaccharides are of the same type and the latter contains more than one type of monosaccharide.

In this post, we will discuss only about monosaccharides.

Characteristics of Monosaccharides:

Lets have a detailed look at monosaccharides which form the basis of all the carbohydrates.

A. Families of Monosaccharides 

Each monosaccharide has a carbonyl group (one of the C-atom is double bonded to an O-atom). Where this carbonyl group is placed in the structure; indicates the type of the monosaccharide. When this carbonyl group is placed at the end of the molecule, then it is aldehyde and the aldehyde-containing monosaccharides are called aldoses. Remember that all aldoses have –CHO at the top and the CH2OH at the bottom (see adjacent figure). Alternatively, when this carbonyl group is present at any other position (except the end as shown in adjacent figure), then it forms a ketone and ketone-containing monosaccharide are called ketoses. Remember that the ketoses have CH2OH at the top as well as the bottom of the molecule.

B. Chiral Center, Enantiomers, Diastereoisomers, Epimers: 

Let us take an example of the smallest and simplest monosaccharide, glyceraldehyde which is a triose to understand what is a chiral center. The central carbon atom here is referred to as the 'chiral center'. A carbon atom is called ‘chiral’ when that carbon atom has four different functional groups attached to it (see the figure below). The compound having a chiral carbon atom is called the chiral compound. These chiral compounds lack a plane of symmetry and exist as two optical isomers which are called as enantiomers. Thus, enantiomers are those isomers that lack the plane of symmetry and exist as two forms in nature as right handed (D-form) or left-handed (L-form) which are non-superimposable. These compounds also have the property of differentially reflecting polarized light. To make it more clear, the two forms of glyceraldehyde (D- and L- glyceraldehyde) are depicted in the figure below. These two isomers are mirror images of each other.  

D and L-sugar: When a monosaccharide or a sugar can be called D-sugar or L-sugar? Monosaccharides are often represented by a Fischer Projection, a shorthand notation particularly useful for showing stereochemistry in straight chained organic compounds.  By convention, when the hydroxyl (-OH) group in the chiral carbon is on the right hand side of the Fischer projection, it is called the D-sugar (or D-isomer) and when the hydroxyl group is on the left hand side, it is the L-sugar (or L-isomer).

Diastereoisomers: Another type of isomerism seen in carbohydrates is diastereoisomers. When the chiral carbons are connected to the exactly same substrates but the configurations are different (R or S), then they are diastereoisomers. Diastereoisomers are NOT mirror images like that of enantiomers. For example, in the adjacent figure, D-glucose and D-altrose are diastereoisomers.

Epimers: The last type of isomerism shown by carbohydrates is epimerism. Epimers are two diastereomers that contain more than one chiral center but differ from each other in the absolute configuration at only one chiral center. For example, in the figure, D-glucose and D-mannose are examples of epimers.

 C. Cyclic Monosaccharides:

Monosaccharides can exist as three different forms - open chain (Fischer projection, mentioned above) and two cyclic forms as alpha (α) and beta (β) sugar. Monosaccharides that have 5, 6 or 7 carbon atoms are often stable in aqueous solutions as they can form cyclic structures as against the open chains. 

How are cyclic structures formed? Cyclic monosaccharides are spontaneously formed by a covalent linkage between the carbonyl carbon and a  hydroxyl group in the carbon backbone. This covalent bond is the result of the reaction between an alcohol group and an aldehyde group of an aldose sugar to a form a hemiacetal or between an alcohol group and the ketone group of a ketose sugar to form a hemiketal. Confused? Okay! To make it more clear, lets take an example as to how

D-glucose cyclization reaction takes place?
Here, the C-5 hydroxyl group of D-glucose attacks the oxygen atom of C-1 aldehyde to form a cyclic hemiacetal (adjacent figure). In this conformation, the C-1 carbon of D-glucose becomes the new chiral center and cyclic forms exists as either β-D-glucose where the hydroxyl group at C-1 is above the plane of the ring or as α-D-glucose where the hydroxyl group is below the plane of the ring (figure at the adjacent makes it clear).
The hemiacetal C-1 carbon atom of cyclic D-glucose is called the anomeric carbon. α-D-glucose and β-D-glucose which are two different forms of cyclic sugars are called anomers as they differ only at anomeric carbon. Cyclic conformations of hexose sugars are called pyranoses (for ex. glucose in cyclic forms will be either α-D-glucopyranose or β-D-glucopyranose)  because the 6-membered ring is similar to a pyran compound. Ketose (like fructose) also forms cyclic structure but the carbonyl is at the C-2 position of the open chain and thus, the ring form contains only 5 carbon atoms. These sugars are called furanoses because they resemble the compound, furan (fructose in cyclic form will be referred to as α-D-fructofuranose or β-D-fructofuranose).

Remember that pyranose rings are much more stable in solution than furanose rings. 

This was all about monosaccharides. In the next post, I have discussed about disaccharides, oligosaccharides and polysaccharides.