Structure and Functions of Biomolecules: Carbohydrates

Introduction to Biomolecules

• Definition of Biomolecules: A biomolecule (or biogenic substance) is any molecule produced by a living organism. This includes both large complex structures and smaller metabolic compounds.

  • Large Biomolecules: Proteins, polysaccharides, lipids, nucleic acids.

  • Small Biomolecules: Primary metabolites, secondary metabolites, natural products.

• Classification by Molecular Size and Weight:

  • Macromolecules:

  • Larger in size with complex structures.

  • High molecular weight, usually $\\ge 10,000\\,\\text{Daltons}$.

  • Examples: Carbohydrates, proteins, lipids, nucleic acids.

  • Micromolecules:

  • Smaller in size with simple structures.

  • Low molecular weight, ranging from $18 - 1800\\,\\text{Daltons}$.

  • Examples: Water, gases, minerals, amino acids, simple sugars, nucleotides.

Overview and Definition of Carbohydrates

• Chemical Definition: Optically active polyhydroxy aldehydes or ketones, or substances that yield polyhydroxy aldehydes or ketones upon hydrolysis.

• Chemical Nature:

  • Hydrates of carbon containing carbon, hydrogen, and oxygen.

  • Elemental ratio of Carbon : Hydrogen : Oxygen is $1:2:1$.

  • General chemical formula: $C_n(H_2O)_n$ or $C(H_2O)$.

• Terminology: Also referred to as saccharides because sugar is their basic fundamental component.

Broad Classification of Carbohydrates

• Carbohydrates are broadly classified into small (monosaccharides and oligosaccharides) and complex (polysaccharides).

1. Monosaccharides

• Simple sugars that cannot be further hydrolyzed into simpler sugar units.

• Characterized by a sweet taste and high solubility in water.

• Examples: Glucose, Fructose, Galactose.

2. Oligosaccharides

• Sugars that yield $2 \\text{ to } 10$ monosaccharide units upon hydrolysis.

• Characterized by a sweet taste and high solubility in water.

• Classification based on sugar unit count:

  • Disaccharides: Contain $2$ monosaccharide units (e.g., Maltose formed of two glucose units; Lactose formed of galactose and glucose; Sucrose formed of glucose and fructose).

  • Trisaccharides: Contain $3$ monosaccharide units, continuing up to $10$ units.

3. Polysaccharides

• Complex carbohydrates consisting of a large number of monosaccharides linked together by glycosidic bonds.

• Homopolysaccharides:

  • Formed by the repetition of a single type of monosaccharide unit.

  • Yield only one type of monosaccharide upon hydrolysis.

  • Examples: Starch, Glycogen, Inulin, Cellulose, Pectin, Chitin.

• Heteropolysaccharides:

  • Composed of a mixture of different types of monosaccharides.

  • Yield a mixture of monosaccharide units upon hydrolysis.

  • Examples: Hyaluronic acid, Chondroitin, Heparin, Agar agar.

Structure and Classification of Monosaccharides

• Elemental Composition: Composed of carbon, hydrogen, and oxygen atoms with the general formula $(CH_2O)_n$, where $n$ represents the number of carbon atoms.

• Valency and Bonding Pattern: Carbon possesses four valencies; it forms two bonds with hydrogen, one bond with oxygen, and one bond with an adjacent carbon atom.

• Functional Group Classification:

  • Aldoses: Contain a carbonyl group at the terminal position, making the functional group an aldehyde.

  • Ketoses: Contain a carbonyl group at the second carbon position (second to terminal), making the functional group a ketone.

• Ring Formation Types:

  • Pyranose Ring: A six-membered closed ring formed when terminal carbons of an aldose undergo dehydration/reaction.

  • Furanose Ring: A five-membered closed ring formed when the carbonyl carbon of a ketose reacts with another terminal end of the same molecule via dehydration.

Detailed Classification and Examples of Aldoses

• Parent Compound: The mother compound of all aldoses is the aldotriose D-glyceraldehyde.

• Theoretical Derivation: Derived by inserting secondary alcohol groups ($\\text{H-C-OH}$) below the aldehyde group of glyceraldehyde.

• Stereochemical Configuration (D and L System):

  • D-Sugars: Possess the hydroxyl group ($\\text{-OH}$) on the penultimate carbon atom (the carbon atom immediately before the last carbon) positioned to the right. Derived from D-glyceraldehyde.

  • L-Sugars: Possess the hydroxyl group ($\\text{-OH}$) on the penultimate carbon atom positioned to the left. Derived from L-glyceraldehyde.

  • Most naturally occurring monosaccharides belong to the D-configuration.

• Classification by Carbon Count:

  • Aldotrioses ($C_3$): D-glyceraldehyde.

  • Aldotetroses ($C_4$): D-erythrose.

  • Aldopentoses ($C_5$): D-ribose, D-xylose.

  • Aldohexoses ($C_6$): D-glucose, D-mannose, D-galactose.

Detailed Classification and Examples of Ketoses

• Structural Features: Contain two terminal primary alcohol groups ($\\text{CH}_2\\text{OH}$) and one internal ketone group ($\\text{C=O}$).

• Parent Compound: The simplest ketose is dihydroxyacetone ($C_3$).

• Theoretical Derivation: Derived by inserting secondary alcohol groups below the ketonic group.

• Classification by Carbon Count:

  • Ketotrioses ($C_3$): Dihydroxyacetone.

  • Ketotetroses ($C_4$): D-erythrulose.

  • Ketopentoses ($C_5$): D-ribulose, D-xylulose.

  • Ketohexoses ($C_6$): D-fructose.

  • Ketoheptoses ($C_7$): D-Sedoheptulose (the only seven-carbon sugar present in humans; synthesized in the body from glucose).

Isomerism in Monosaccharides

Asymmetric Carbon Atoms and Stereoisomers

• Asymmetric Carbon: A carbon atom bonded to four entirely different atoms or groups of atoms. All monosaccharides contain one or more asymmetric carbon atoms, except dihydroxyacetone.

• Stereoisomers: Isomeric molecules with identical molecular formulas and bonding sequences, but differing three-dimensional spatial arrangements of atoms.

• Formula for Optical Isomers: The total number of stereoisomers is calculated as $2^n$, where $n$ is the number of asymmetric carbon atoms in the molecule.

Isomer Counts in Aldoses

• Aldotrioses: Contain $1$ asymmetric carbon atom; $2^1 = 2$ optical isomers (D-glyceraldehyde and L-glyceraldehyde).

• Aldotetroses: Contain $2$ asymmetric carbon atoms; $2^2 = 4$ optical isomers ($2$ in D-form, $2$ in L-form).

• Aldopentoses: Contain $3$ asymmetric carbon atoms; $2^3 = 8$ optical isomers ($4$ in D-form, $4$ in L-form).

• Aldohexoses: Contain $4$ asymmetric carbon atoms; $2^4 = 16$ optical isomers ($8$ in D-form, $8$ in L-form).

Isomer Counts in Ketoses

• Ketoses possess one less asymmetric carbon atom than their corresponding aldoses of equal carbon length.

• Ketotetroses: Contain $1$ asymmetric carbon atom; $2^1 = 2$ optical isomers (D and L).

• Ketopentoses: Contain $2$ asymmetric carbon atoms; $2^2 = 4$ optical isomers.

• Ketohexoses: Contain $3$ asymmetric carbon atoms; $2^3 = 8$ optical isomers.

• In all cases, exactly half of the isomers exist in the D-form and the other half in the L-form.

• Mammalian metabolic enzymes are stereospecific for D-configuration sugars.

Enantiomers

• Non-superimposable mirror images of each other represented by D- and L-forms of the exact same compound.

• Example: D-glucose and L-glucose.

Optical Activity

• The capacity of a substance containing asymmetric carbon atoms to rotate Plane Polarized Light (PPL).

• Dextrorotation: Rotation of PPL to the right (clockwise), designated by small letter $d$ or sign $+$.

  • Naturally occurring D-glucose is dextrorotatory, designated as D(+) glucose (+52.5^\\circ) or dextrose.

• Levorotation: Rotation of PPL to the left (counter-clockwise), designated by small letter $l$ or sign $-$.

  • Naturally occurring D-fructose is levorotatory, designated as D(-) fructose (-92.3^\\circ) or levulose.

• All monosaccharides demonstrate optical activity except dihydroxyacetone, which lacks an asymmetric carbon.

Cyclic Structures, Anomers, Epimers, and Functional Isomerism

Anomers (Cyclic Structure Formation)

• Aldohexose Ring Formation (Glucose):

  • In solution, the aldehyde group at $C_1$ combines with the hydroxyl group at $C_5$.

  • Forms a 6-membered heterocyclic pyranose ring containing 5 carbons and 1 oxygen atom.

  • Linkage formed between the aldehyde and alcohol group is called a hemiacetal linkage.

• Ketohexose Ring Formation (Fructose):

  • The ketone group at $C_2$ combines with the hydroxyl group at C_5$.\n * Forms a 5-membered furanose ring.\n * Linkage formed between the keto and alcohol group is called a **hemiketal** linkage.\n* **Haworth Projection Rules**:\n * Ring edge closest to the reader is drawn with thick lines.\n * Groups on the left side of the open-chain structure project **upward**.\n * Groups on the right side of the open-chain structure project **downward**.\n * For D-sugars, C_6$projects **upward**; for L-sugars,$C_6 projects **downward**.\n* **Anomeric Carbon and Anomeric Forms**:\n * Cyclization generates a new asymmetric carbon center termed the **anomeric carbon** (C_1$in aldoses,$C_2 in ketoses).\n * **\alpha-Form**: In D-sugars, the hydroxyl group on the anomeric carbon is to the right (projected downward in Haworth).\n * **\beta-Form**: In D-sugars, the hydroxyl group on the anomeric carbon is to the left (projected upward in Haworth).\n* **Equilibrium Behavior in Solution**:\n * **D-Glucose**: At 20\,^\circ\text{C}$, glucose in solution exists as approximately$\frac{1}{3}$($33\%$)$\alpha$-form,$\frac{2}{3}$($66\%$)$\beta-form, and trace amounts of open-chain aldehyde form (intermediate stage).\n * **D-Fructose**: Exists in two distinct cyclic forms:\n 1. *Furanose*: Ring closure between C_5$and$C_2; found bound in sucrose and inulin.\n 2. *Pyranose*: Ring closure between C_6$and$C_2; found when free in aqueous solution.\n * **D-Ribose**: Ring closure occurs between C_4$and$C_1$to yield$\alpha\text{-D-ribofuranose}$or$\beta\text{-D-ribofuranose}.\n\n## Epimers\n* Compounds containing multiple asymmetric carbons that differ in spatial configuration around only one specific carbon atom.\n* Examples:\n * D-Glucose and D-Mannose are epimers at C_2\n * D-Glucose and D-Galactose are epimers at C_4\n* Anomers represent a specific subclass of epimers at C_1$(for cyclic aldoses) or$C_2 (for cyclic ketoses).\n\n## Aldose-Ketose Isomers (Functional Group Isomerism)\n* Isomers possessing identical molecular formulas but differing functional groups.\n* Example: Fructose is a functional group isomer of glucose, galactose, and mannose.\n\n# Monosaccharide Nomenclature and General Properties\n\n## Nomenclature Rules\n* Categorized based on carbon atom count, ending with suffix '-ose':\n * 2 Carbons: Diose\n * 3 Carbons: Triose\n * 4 Carbons: Tetrose\n * 5 Carbons: Pentose\n * 6 Carbons: Hexose\n * 7 Carbons: Heptulose\n\n## Physicochemical Properties\n1. Solid crystalline state at room temperature.\n2. Highly water-soluble with a characteristically sweet taste.\n3. Dehydration reaction among multiple monosaccharide hydroxyl groups forms glycosidic bonds to build disaccharides, trisaccharides, or polysaccharides.\n4. Stereoisomerism: Exist in D- and L-conformations. D-conformations predominate in biological systems, whereas L-conformations are synthetically prepared in laboratory environments.\n\n# Biologically Important Monosaccharides\n\n## Glucose\n* Six-carbon aldose sugar; forms a pyranose closed ring.\n* Primary source of chemical energy in biological systems.\n* Storage forms: Starch in plants, Glycogen in animals.\n* The human brain depends exclusively on carbohydrates in the form of glucose for its energy needs.\n\n## Fructose\n* Six-carbon ketose sugar (fruit sugar); forms a furanose closed ring.\n* Functions as an efficient biological energy source.\n* Condenses with glucose via dehydration to produce sucrose.\n\n## Galactose\n* Hexose sugar predominantly found in milk.\n* Condenses with glucose via dehydration to produce lactose.\n* Serves as the sole energy source for growing infants, being subsequently converted to glucose in the body.\n\n# Disaccharides\n\n* Composed of two monosaccharides joined together by a glycosidic linkage.\n\n## Classification by Reducing Ability\n* **Reducing Disaccharides**: Retain a free, unbonded anomeric carbon on the second sugar unit. Mutarotate and exist in both \alpha$and$\beta structural forms.\n* **Non-Reducing Disaccharides**: Glycosidic linkage involves the anomeric/carbonyl carbons of both participating sugar units, leaving no free anomeric carbon.\n\n## Reducing Disaccharides\n* **Maltose (Malt Sugar)**:\n * Structure: Two D-glucopyranose units joined by an \alpha 1, 4-glucosidic linkage.\n * Exists in both \alpha$and$\beta forms.\n * Primary digestion product of starch produced by amylase action.\n * Cleaved into two D-glucose molecules by maltase enzyme or acid hydrolysis.\n* **Isomaltose**:\n * Structure: Two D-glucopyranose units joined by an \alpha 1, 6-glucosidic linkage.\n * Hydrolysis product of starch and glycogen by amylase; forms the structural branching point.\n* **Lactose (Milk Sugar)**:\n * Structure: \beta\text{-D-galactopyranose}$and D-glucopyranose joined by a$\beta 1, 4-galactosidic linkage.\n * Cleaved into D-glucose and D-galactose by lactase enzyme or acid hydrolysis.\n\n## Non-Reducing Disaccharides\n* **Sucrose (Cane Sugar / Table Sugar)**:\n * Occurs naturally in sugar cane and beets.\n * Structure: \beta\text{-D-fructofuranose}$and$\alpha\text{-D-glucopyranose}$joined by an$\alpha 1, 2$-glucosidic linkage or$\beta 2, 1-fructosidic linkage.\n * Non-reducing because both anomeric carbons (C_1$of glucose,$C_2 of fructose) participate directly in the glycosidic bond.\n\n# Oligosaccharides\n\n* Polymers consisting of 3 - 10 monosaccharide units.\n* Dietary significance: Minor dietary energy source for humans due to non-digestibility of most forms.\n* Structural significance: Critical structural constituents of biological molecules:\n * ABO blood group substances.\n * Immunoglobulins.\n * Glycolipids and glycoproteins embedded within cell membranes.\n\n# Polysaccharides and Homopolysaccharides\n\n* Polymers composed of more than 10 monosaccharide units joined by glycosidic bonds.\n* Non-reducing nature: Condensation consumes nearly all carbonyl groups, leaving only one single free carbonyl group at the end of a massive macromolecule.\n\n## Homopolysaccharides\n* Polysaccharides constructed from only one single repeating monosaccharide type.\n* Named based on constituent monomer units:\n * **Glucans**: Constructed exclusively from D-glucose units (e.g., Starch, Dextrins, Glycogen, Cellulose).\n * **Fructans**: Constructed exclusively from D-fructose units (e.g., Inulin in plants).\n\n## Starch\n* Primary carbohydrate storage polymer in chlorophyll-bearing plants.\n* Found in high concentrations in cereals (rice, wheat), tubers (potatoes, sweet potatoes), and legumes (beans).\n* Granular composition consists of two distinct structural fractions:\n 1. **Amylose** (15 - 20\% of starch granule):\n * Located in the inner portion of the granule.\n * Unbranched linear chain composed of 300 - 400$(up to$1000$) D-glucopyranose units linked by$\alpha 1, 4-glucosidic bonds.\n 2. **Amylopectin** (80 - 85\%$$ of starch granule):

    • Located in the outer portion of the granule.