CELLULOSE

Cellulose is a polysaccharide that occurs exclusively in plants and is recognized as the most abundant organic substance in the plant kingdom. It serves as a predominant constituent of plant cell walls and is completely absent in the animal body. Cellulose is composed of β-D-glucose units linked together by β-1,4-glycosidic bonds.

Digestion of Cellulose

Despite its importance, cellulose cannot be digested by mammals, including humans, due to the lack of the enzyme required to cleave β-glycosidic bonds; for instance, α-amylase only breaks α bonds.

Biomedical Importance of Cellulose

Although not digestible, cellulose plays a significant role in human nutrition. It is a major component of dietary fiber, which is a non-digestible carbohydrate. The functions of dietary fiber include:

• Decreasing the absorption of glucose and cholesterol from the intestine.

• Increasing the bulk of feces.

• Acting as a stool softener, thereby helping prevent constipation.

The consumption of cellulose has been correlated with a reduced incidence of various diseases, including:

• Cardiovascular disease.

• Colon cancer.

• Diabetes.

• Diverticulosis.

HETEROPOLYSACCHARIDES

Definition

Heteropolysaccharides are complex carbohydrates made up of more than ten different repeating units.

MUCOPOLYSACCHARIDES (MPS) or GLYCOSAMINOGLYCANS (GAGS)

Mucopolysaccharides, also known as glycosaminoglycans, are significant components of various biological systems.

Types and Examples of Mucopolysaccharides

• Acidic Non-Sulfated MPS:
  Hyaluronic Acid

• Acidic Sulfated MPS:
    1. Heparin
    2. Heparan Sulfate
    3. Chondroitin Sulfate
    4. Dermatan Sulfate
    5. Keratan Sulfate

SUMMARY OF GLYCOSAMINOGLYCANS

HYALURONIC ACID

Hyaluronic acid is an important glycosaminoglycan found in the ground substance of synovial fluid in joints and the vitreous humor of the eyes. It is present in connective tissues and forms a protective gel around the ovum. Its functions include:

• Lubrication: Reduces friction in joints.

• Shock Absorption: Acts as a shock absorber in joints.

• Developmental Roles: Involved in processes like tumor metastasis, angiogenesis, and blood coagulation.

CHONDROITIN SULFATES

Chondroitin 4-sulfate is a major constituent of various mammalian tissues such as bone, cartilage, tendons, heart valves, skin, and cornea. It is composed of D-glucuronic acid and N-acetyl-D-galactosamine 4-sulfate and provides resistance against compression in cartilage.

HEPARIN

Heparin is an anticoagulant that occurs in various tissues, including the blood, lung, liver, kidney, and spleen. It is composed of alternating units of N-sulfo-D-glucosamine 6-sulfate and glucuronate 2-sulfate. Its role includes helping release lipoprotein lipase, which clears lipemic plasma.

DERMATAN SULFATE

Dermatan sulfate is closely related to chondroitin 4-sulfate with an inversion at C5, forming L-iduronic acid instead. It is involved in wound healing, blood coagulation regulation, infection responses, and cardiovascular defense.

CYCLIC STRUCTURE OF MONOSACCHARIDES

Reactions Involving Aldehyde and Keto Groups

Monosaccharides can react with aldehyde and ketone functional groups to form hemiacetals and hemiketals. The hydroxyl group of monosaccharides reacts with its own aldehyde or keto functional group. This reaction results in:

• Cyclic Hemiacetals: The aldehyde group of glucose at C-1 reacts with the hydroxyl group at C-5 or C-4 to form cyclic structures (pyranose for six-membered and furanose for five-membered).

Anomeric Carbon

After ring formation, carbon 1 becomes asymmetrical, termed the anomeric carbon atom. The hydroxyl group bound to this carbon is referred to as the anomeric hydroxyl group.

PREFERRED STRUCTURAL FORM

The more stable structural forms of many monosaccharides, such as glucose, are in cyclic configurations, which helps mitigate angular and steric strain associated with other forms.

GLUCOSE STRUCTURE

The structure of glucose can be represented in the following forms:

1. Straight-chain structural formula (Fisher projection)

2. Cyclic formula (Haworth projection)

In solution, glucose predominantly exists as a six-membered ring (glucopyranose), which is more thermodynamically stable than the five-membered form (glucofuranose).

FISCHER PROJECTIONS

The Fischer projection of D-glucose illustrates its straight-chain structure:

$ext{D-Glucose (Fischer projection)}$

RING STRUCTURE OF GLUCOSE

The Haworth projection illustrates the ring structure of glucose:
$ext{D-Glucopyranose (Haworth projection)}$

KERATAN SULFATE

Keratan sulfate is a heterogeneous glycosaminoglycan with variable sulfate content and consists mainly of alternating units of D-galactosamine and N-acetylglucosamine 6-sulfate. It is found in cornea, cartilage, and bones and acts as a cushion to absorb mechanical shocks in joints.

BLOOD GROUP SUBSTANCES

The blood groups (A, B, AB, and O) contain antigens located on the erythrocyte membrane, composed of carbohydrates present as glycoproteins or glycolipids. The carbohydrates involved include:

• N-Acetylgalactosamine

• Galactose

• Fructose

• Sialic acid

The carbohydrate content serves a critical role in blood grouping.

OPTICAL ACTIVITY & STEREOISOMERISM

Asymmetric Carbon Atom

An asymmetric carbon atom has four different groups or atoms attached. Substances containing asymmetric carbon atoms exhibit optical activity and stereoisomerism. All carbohydrates, apart from dihydroxyacetone (DHA), contain asymmetric carbon atoms.

Presence of Asymmetric Carbon Atoms

The presence of asymmetric carbon atoms gives rise to:

1. Optical Activity: The ability of a substance to rotate the plane of polarized light.

2. Stereoisomerism: The condition where compounds with the same molecular formula differ in spatial configuration.

Types of Stereoisomerism

• D and L isomers (Enantiomers)

• Epimers: Monosaccharides differing from one another at a single asymmetric carbon (other than the anomeric carbon).

• Anomers: Special case of epimers that differ specifically at the anomeric carbon.

CHIRALITY AND SUPERIMPOSED IMAGES

Chiral objects cannot be superimposed. They are categorized into:

• Chiral carbon: asymmetric carbon atoms.

• Achiral carbon: symmetrical carbon atoms.

ISOMERISM

Definition

Isomerism encompasses compounds with the same molecular formula, functional groups, and position of functional groups but differing in structure or spatial configurations. Various types include:

• Structural Isomers: Different structural arrangements.

• Functional Isomers: Isomers with different functional groups.

• Positional Isomers: Substituents placed on different carbon atoms.

• Cis-Trans Isomers: Differences in spatial arrangement around double bonds.

The number of isomers possible is determined by the formula $2^n$, where n is the number of asymmetric carbon atoms in a molecule. For example, glucose possesses four asymmetric carbon atoms, resulting in $2^4 = 16$ potential isomers.

D-AND L-ISOMERS

The configuration around the carbon atom adjacent to the terminal primary alcohol carbon defines whether a sugar is classified as D or L:

• If the -OH group on this carbon is on the right side, it belongs to the D series.

• If on the left side, it is designated as L.

ANOMERS

Anomers are a specific type of stereoisomer found in cyclic forms of monosaccharides where the anomeric carbon is involved. In Haworth projections:

• The α-anomer has the anomeric hydroxyl below the ring plane.

• The β-anomer has the anomeric hydroxyl above the ring plane.

MUTAROTATION

Mutarotation refers to the spontaneous conversion of one anomer to another, resulting in a mixture of anomers in solution at equilibrium (approximately 36% α-anomer and 64% β-anomer with <1% open-chain form).

RACEMIC MIXTURE: A racemic mixture occurs when D- and L-isomers are present in equal proportions, canceling out each other’s optical activity, thus rendering the mixture optically inactive.

CHEMICAL PROPERTIES OF CARBOHYDRATES

Osazone Formation

Osazones are carbohydrate derivatives formed when sugars react with an excess of phenylhydrazine, producing yellow or orange crystalline structures that can be used to identify and characterize different sugars (e.g., glucosazone).

Benedict's Test

In Benedict's test, reducing sugars, when heated with an alkaline solution, convert to strong reducing agents (enediols), turning the solution an orange-red/brick-red upon the addition of Benedict's reagent. Monosaccharides such as D-glucose oxidize into D-gluconic acid and are classified as reducing sugars.

Reduction to Alcohols

Carbohydrates can reduce their open-chain C=O groups to alcohols using sodium borohydride (NaBH₄) or through catalytic hydrogenation, resulting in products known as alditols.

MONOSACCHARIDE DERIVATIVES

Ester Formation

Monosaccharides can form esters with phosphoric acids when their hydroxyl groups react, producing compounds like glucose-1-phosphate or glucose-6-phosphate. This phosphorylation is crucial in preventing the diffusion of sugars out of cells and is also an integral part of RNA and DNA.

Sugar Alcohols

Reduction of monocaccharides results in sugar alcohols, such as D-sorbitol or D-mannitol, with both potentially causing osmotic effects in tissues, leading to conditions like cataracts or peripheral neuropathy when accumulated in high amounts. Mannitol can serve clinical applications, such as reducing intracranial pressure.

Glycosidic Bonds

The glycosidic bonds are formed between the anomeric carbon of a carbohydrate and a hydroxyl oxygen of an alcohol (O-glycosidic bond) or the nitrogen of an amine (N-glycosidic bond). Glycosidic bonds link monosaccharides to form oligo- and polysaccharides, resulting in non-reducing sugars when the ring structure is stabilized.

Sugar Acids

Oxidation of the aldehyde group to a carboxylic acid yields gluconic acid, while oxidation of the terminal alcohol group can produce glucuronic acid.