Biomolecules: Classification, Structure, and Biological Functions

Introduction to Biochemistry and Biomolecules

• A living system is a complex entity that grows, sustains, and reproduces itself, despite being composed of non-living atoms and molecules.

• Biochemistry is the domain of science that investigates the chemical processes occurring within living systems.

• Living systems consist of various complex biomolecules, including:

  • Carbohydrates

  • Proteins

  • Nucleic acids

  • Lipids

• In addition to complex molecules, simple molecules such as vitamins and mineral salts are essential for the biological functions of organisms.

• Biomolecules like proteins and carbohydrates are essential constituents of food. They interact with one another to constitute the "molecular logic of life processes."

• A key principle of biology is that the harmonious and synchronous progress of chemical reactions in the body leads to life.

Classification and Properties of Carbohydrates

• Carbohydrates are primarily produced by plants and represent a large group of naturally occurring organic compounds.

• Common examples include cane sugar, glucose, and starch.

• Historical Definition: Carbohydrates were originally considered "hydrates of carbon" because many fit the general formula $C_x(H_2O)_y$.

  • Example: Glucose ($C_6H_{12}O_6$) fits as $C_6(H_2O)_6$.

  • Exceptions to the formula: Acetic acid ($CH_3COOH$) fits as $C_2(H_2O)_2$ but is not a carbohydrate. Rhamnose ($C_6H_{12}O_5$) is a carbohydrate but does not fit the formula.

• Modern Chemical Definition: Carbohydrates are defined as optically active polyhydroxy aldehydes or ketones, or compounds that produce such units upon hydrolysis.

• Saccharides: Derived from the Greek word "sakcharon" meaning sugar, carbohydrates are also known as saccharides.

• Classification based on Hydrolysis:

  1. Monosaccharides: Carbohydrates that cannot be further hydrolysed into simpler units of polyhydroxy aldehydes or ketones. Approximately $20$ are found in nature (e.g., glucose, fructose, ribose).

  2. Oligosaccharides: Carbohydrates that yield two to ten monosaccharide units on hydrolysis. They are sub-classified as disaccharides, trisaccharides, tetrasaccharides, etc.

     • Disaccharides are the most common.

     • Hydrolysis examples: Sucrose yields one glucose and one fructose molecule; Maltose yields two glucose molecules.

  3. Polysaccharides: Carbohydrates yielding a large number of monosaccharide units on hydrolysis. Examples include starch, cellulose, glycogen, and gums. They are generally not sweet and are termed "non-sugars."

• Reducing and Non-reducing Sugars:

  • Reducing Sugars: Carbohydrates that reduce Fehling’s solution and Tollens’ reagent. All monosaccharides (aldoses and ketoses) are reducing sugars.

  • Non-reducing Sugars: Carbohydrates (like sucrose) where the reducing groups (aldehyde or ketone) are involved in glycosidic linkages.

Structure and Preparation of Glucose

• Glucose is an aldohexose, also known as dextrose. It is the monomer for starch and cellulose and is likely the most abundant organic compound on Earth.

• Preparation:

  1. From Sucrose (Cane Sugar): Boiling sucrose with dilute $HCl$ or $H_2SO_4$ in alcoholic solution yields equal amounts of glucose and fructose.

     • $C_{12}H_{22}O_{11} + H_2O \rightarrow C_6H_{12}O_6 \text{ (Glucose)} + C_6H_{12}O_6 \text{ (Fructose)}$

  2. From Starch (Commercial): Hydrolysis of starch by boiling with dilute $H_2SO_4$ at $393\,K$ under $2-3\,atm$ pressure.

     • $(C_6H_{10}O_5)_n + nH_2O \rightarrow nC_6H_{12}O_6$

• Evidence for Glucose Structure ($C_6H_{12}O_6$):

  1. n-Hexane Formation: Heating with $HI$ produces n-hexane, proving all six carbons are in a straight chain.

  2. Carbonyl Group: Reacts with hydroxylamine to form an oxime and adds $HCN$ to give cyanohydrin.

  3. Aldehydic Group: Oxidation with bromine water (a mild oxidant) yields gluconic acid ($C_6H_{12}O_7$).

  4. Five Hydroxyl Groups: Acetylation with acetic anhydride yields glucose pentaacetate, confirming five $-OH$ groups on different carbons.

  5. Primary Alcoholic Group: Oxidation of glucose or gluconic acid with nitric acid yields saccharic acid (a dicarboxylic acid), indicating one primary alcohol group.

• Configuration:

  • Represented as $D(+)$-glucose.

  • ‘D’ denotes the configuration (relative to $D(+)$-glyceraldehyde where the $-OH$ is on the right side of the lowest asymmetric carbon).

  • ‘(+)’ denotes that the molecule is dextrorotatory.

  • The structure is written so the most oxidized carbon ($-CHO$) is at the top.

Cyclic Structure and Anomerism of Glucose

• Limitations of Open Chain Structure:

  1. Glucose does not give Schiff’s test or form hydrogensulphite addition products with $NaHSO_3$.

  2. Glucose pentaacetate does not react with hydroxylamine (suggesting no free $-CHO$ group).

  3. Existence of two crystalline forms: $\alpha$ (m.p. $419\,K$, crystallized at $303\,K$) and $\beta$ (m.p. $423\,K$, crystallized at $371\,K$).

• Proposed Structure: Glucose forms a six-membered cyclic hemiacetal ring involving the $-OH$ at $C_5$ and the $-CHO$ group.

• Anomers: The two cyclic forms ($\alpha$ and $\beta$) differ only in the configuration at $C_1$, known as the anomeric carbon. These isomers are called anomers.

• Pyranose Structure: The six-membered ring is named pyranose due to its analogy with pyran (a five-carbon, one-oxygen heterocyclic ring).

• Haworth Structures: These provide a more accurate representation of the cyclic arrangement.

Fructose and Disaccharides

• Fructose:

  • An important ketohexose found in fruits and honey.

  • Formula: $C_6H_{12}O_6$. It has a ketone group at $C_2$ and a straight chain of six carbons.

  • It belongs to the D-series and is laevorotatory ($D(-)$-fructose).

  • Forms a five-membered cyclic hemiacetal called furanose (analogy to furan).

• Disaccharides:

  • Formed by the loss of a water molecule between two monosaccharides, creating an oxide linkage called a glycosidic linkage.

  • Sucrose: Linkage between $C_1$ of $\alpha$-D-glucose and $C_2$ of $\beta$-D-fructose. It is a non-reducing sugar.

    • Invert Sugar: Sucrose ($+66.5^{\circ}$) is dextrorotatory, but its hydrolysis product is laevorotatory because fructose's laevorotation ($-92.4^{\circ}$) exceeds glucose's dextrorotation ($+52.5^{\circ}$).

  • Maltose: Composed of two $\alpha$-D-glucose units linked by $C_1$ of one unit to $C_4$ of the other. It is a reducing sugar.

  • Lactose (Milk Sugar): Composed of $\beta$-D-galactose and $\beta$-D-glucose with a $C_1-C_4$ linkage. It is a reducing sugar.

Polysaccharides

• Starch: Main storage polysaccharide in plants.

  • Composed of $\alpha$-glucose monomers.

  • Amylose: Water-soluble ($15-20\%$), unbranched long chain ($200-1000$ units) with $C_1-C_4$ linkages.

  • Amylopectin: Insoluble in water ($80-85\%$), branched-chain polymer. Branching occurs via $C_1-C_6$ linkages; main chain is $C_1-C_4$.

• Cellulose: Most abundant organic substance in the plant kingdom; found in cell walls.

  • Straight chain polysaccharide of $\beta$-D-glucose units linked by $C_1-C_4$ glycosidic bonds.

• Glycogen (Animal Starch): Storage form in animals (liver, muscles, brain). Similar to amylopectin but more highly branched.

Proteins and Amino Acids

• Proteins: Derived from "proteios" (primary importance). They are polymers of $\alpha$-amino acids.

• Amino Acids: Contain both amino ($-NH_2$) and carboxyl ($-COOH$) groups attached to the same (alpha) carbon.

  • Zwitter Ion: In aqueous solution, the carboxyl group loses a proton and the amino group accepts one, forming a dipolar ion. This makes amino acids amphoteric.

  • Chirality: All naturally occurring $\alpha$-amino acids (except glycine) are optically active with L-configuration.

  • Essential vs. Non-essential: Essential amino acids cannot be synthesized by the body and must be acquired via diet (e.g., Valine, Leucine). Non-essential ones can be synthesized by the body (e.g., Glycine, Alanine).

• Peptide Bond: Chemically an amide ($-CO-NH-$) formed between the $-COOH$ of one amino acid and the $-NH_2$ of another with the loss of water.

  • Dipeptides (2 amino acids), Tripeptides (3), Polypeptides (>$10$), Proteins (>$100$ amino acids or mass >$10,000\,u$).

Protein Structure and Denaturation

• Classification by Shape:

  • Fibrous: Parallel polypeptide chains held by hydrogen and disulphide bonds; insoluble in water (e.g., keratin, myosin).

  • Globular: Chains coil into spherical shapes; soluble in water (e.g., insulin, albumin).

• Levels of Structure:

  1. Primary: Specific sequence of amino acids.

  2. Secondary: Folding of the backbone ($\alpha$-helix or \beta$-pleated sheet) due to hydrogen bonding.\n 3. **Tertiary:** Further folding into fibrous or globular shapes; stabilized by H-bonds, disulphide links, van der Waals, and electrostatic forces.\n 4. **Quaternary:** Spatial arrangement of multiple polypeptide subunits.\n* **Denaturation:** Loss of biological activity due to physical (heat) or chemical (pH) changes. Globules unfold and helices uncoil. Primary structure remains intact. Examples: Coagulation of egg white, curdling of milk.\n\n# Enzymes and Vitamins\n\n* **Enzymes:** Biocatalysts, usually globular proteins. They are highly specific.\n * Mechanism: They lower the activation energy (E_a).\n * Example: Sucrose hydrolysis energy drops from 6.22\,kJ\,mol^{-1}$to$2.15\,kJ\,mol^{-1} using sucrase.\n* **Vitamins:** Organic compounds required in small amounts for health.\n * **Fat Soluble:** A, D, E, K (stored in liver/adipose tissue).\n * **Water Soluble:** B group and Vitamin C (excreted in urine; regular intake required, except B_{12}).\n* **Deficiency Diseases:**\n * **Vitamin A:** Xerophthalmia, Night blindness.\n * **Vitamin B1 (Thiamine):** Beri beri.\n * **Vitamin B2 (Riboflavin):** Cheilosis.\n * **Vitamin C (Ascorbic Acid):** Scurvy.\n * **Vitamin D:** Rickets, Osteomalacia.\n * **Vitamin K:** Increased blood clotting time.\n\n# Nucleic Acids and Hormones\n\n* **Nucleic Acids:** Particles in the nucleus (chromosomes) responsible for heredity. They are polynucleotides.\n * **DNA (Deoxyribonucleic Acid):** Contains 2$-deoxy-$\beta-D-ribose sugar. Bases: Adenine (A), Guanine (G), Cytosine (C), Thymine (T).\n * **RNA (Ribonucleic Acid):** Contains \beta-D-ribose sugar. Bases: A, G, C, Uracil (U).\n * **Components:**\n * **Nucleoside:** Base + sugar (1' position).\n * **Nucleotide:** Nucleoside + phosphoric acid (5' position).\n * **DNA Structure:** Watson and Crick proposed a double strand helix with complementary base pairing (A-T, C-G) via hydrogen bonds.\n * **Function:** DNA handles heredity and protein synthesis messages. RNA (m-RNA, r-RNA, t-RNA) carries out protein synthesis.\n* **DNA Fingerprinting:** A unique sequence of bases used in forensics, paternity tests, and identifying dead bodies.\n* **Hormones:** Intercellular messengers produced by endocrine glands.\n * **Steroids:** Estrogens, androgens.\n * **Polypeptides:** Insulin (lowers blood glucose), Glucagon (raises blood glucose).\n * **Amino Acid Derivatives:** Epinephrine, Norepinephrine, Thyroxine (thyroid function; low levels cause hypothyroidism).\n\n# Questions & Discussion\n\n* **Why are glucose/sucrose soluble in water but cyclohexane/benzene is not?** Glucose and sucrose contain multiple -OH groups that form extensive hydrogen bonds with water, whereas cyclohexane and benzene are non-polar hydrocarbons.\n* **What are the hydrolysis products of lactose?** Lactose yields \beta$-D-galactose and$\beta-D-glucose.\n* **Why does glucose pentaacetate not react with hydroxylamine?** Because the aldehydic group is involved in the cyclic hemiacetal formation and is locked in the acetylated form, meaning no free -CHO is available for reaction.\n* **Why can't Vitamin C be stored?** It is water-soluble and easily excreted in urine.\n* **What happens to water in a boiled egg?** During denaturation, the proteins coagulate and entrap the water molecules within the newly formed fibrous or globular networks.\n* **What are the products of hydrolysis of a DNA nucleotide with thymine?** It yields 2$-deoxy-$\beta$$-D-ribose, phosphoric acid, and the nitrogenous base thymine.