Biomolecules

Carbohydrates: Polyhydroxy aldehydes/ketones or compounds that hydrolyze to them. General formula: $C_x(H_2O)_y$ (historically called "hydrates of carbon"). Most carbohydrates are optically active.

Classification:

Monosaccharide nomenclature: -ose suffix.

• By # carbons: triose (3), tetrose (4), pentose (5), hexose (6), heptose (7)
• By carbonyl type: aldose (CHO), ketose (C=O internal)
• Combinations: aldopentose (e.g., ribose), ketohexose (e.g., fructose), aldohexose (e.g., glucose)

D/L Configuration: Based on highest-numbered chiral C relative to glyceraldehyde reference. D = -OH right in Fischer projection; L = -OH left.

Reducing vs Non-reducing Sugars:

• Reducing: Free aldehyde/ketone group; reduces Tollens', Fehling's. (Glucose, fructose, maltose, lactose)
• Non-reducing: No free carbonyl (anomeric C is locked in glycosidic bond). (Sucrose)

Glucose ($C_6H_{12}O_6$): Most important monosaccharide. Aldohexose.

Open Chain Structure (Fischer Projection):

• 6 C, with 5 C chain having OH groups; CHO at C1, primary OH at C6
• Chiral centers at C2, C3, C4, C5 (4 chiral centers, $2^4 = 16$ stereoisomers)
• D-glucose: all OH on right except at C3 (which is on left, by Fischer convention)

Cyclic Structure (Haworth Projection):

Open chain glucose forms hemiacetal: C1 carbonyl + C5 -OH → 6-membered ring (pyranose).

Two forms:

• α-D-glucose: -OH at C1 below the ring (anomeric)
• β-D-glucose: -OH at C1 above the ring

Mutarotation: In aqueous solution, α and β forms interconvert via open-chain form: α-D-glucose ⇌ open chain ⇌ β-D-glucose.

Equilibrium: ~64% β, ~36% α, 0.02% open chain. Specific rotation changes from $+112°$ (pure α) to $+19°$ (pure β) → equilibrium $+52.7°$.

Fructose ($C_6H_{12}O_6$): Ketohexose.

• C2 has C=O group
• Cyclic: 5-membered ring (furanose); C2 to C5 -OH.
• Sweeter than sucrose.

Reactions of Glucose:

1. Oxidation:

• Mild (Br₂/water): $C_6H_{12}O_6 \to C_6H_{12}O_7$ (gluconic acid; CHO → COOH at C1)
• Strong (HNO₃): saccharic acid (both ends to COOH)
• With Tollens'/Fehling's: positive (reducing sugar; gives gluconate)

2. Reduction:

• NaBH₄ / Na/Hg: glucose → sorbitol (hexitol; all OH groups)
• Catalytic H₂: same

3. Hydroxylamine: Forms oxime; confirms CHO group (in open chain).

4. HCN addition: Forms cyanohydrin; confirms carbonyl.

5. Phenylhydrazine (excess): Forms osazone (yellow crystalline ppt; same osazone formed for glucose, mannose, fructose — they only differ in C1 and C2).

6. Tollens' and Fehling's tests: Both positive (glucose is reducing).

7. Acetylation: With acetic anhydride, all 5 -OH become acetates: gluconic acid acetate.

8. Methylation: -OH → -OCH₃ groups.

Disaccharides:

1. Sucrose ($C_{12}H_{22}O_{11}$): "Table sugar." α-D-glucose + β-D-fructose joined at C1-C2 (1,2-glycosidic bond).

• Non-reducing (no free anomeric C).
• Hydrolysis: + dilute acid or invertase → glucose + fructose (mixture is "invert sugar" — laevorotatory due to fructose's high rotation in opposite direction). Original sucrose dextro; product is laevo: rotation inverts, hence name inversion of sucrose.
• Specific rotation: $+66.5°$ (sucrose) → $-39.7°$ (equimolar mix glucose [+52.7°] + fructose [-92.4°]).

2. Maltose: Two α-D-glucose units joined α(1,4). Reducing.

3. Lactose: β-D-galactose + β-D-glucose joined β(1,4). Reducing.

Polysaccharides:

1. Starch: Storage carbohydrate in plants.

• Mix of amylose (~20%, linear, α(1,4)-linked glucose, helical) and amylopectin (~80%, branched, α(1,4) chains with α(1,6) branches).
• Test: blue color with iodine solution (amylose-iodine inclusion complex).

2. Cellulose: Structural carbohydrate in plant cell walls.

• Linear, β(1,4)-linked D-glucose.
• Humans cannot digest (no $\beta$-glucosidase).
• Important fibre.

3. Glycogen: Animal starch, stored in liver and muscles.

• Highly branched; α(1,4) and α(1,6) like amylopectin but more branched.

Amino Acids: Building blocks of proteins. Contains both $-NH_2$ (basic) and $-COOH$ (acidic) groups.

General formula: $RCH(NH_2)COOH$ (R is the side chain that varies).

20 standard amino acids found in proteins. All are α-amino acids (-NH₂ on α-C, adjacent to -COOH).

Classification by R Group:

Essential vs Non-essential:

• Essential: Cannot be synthesized in body; must come from diet (e.g., valine, leucine, lysine, threonine, methionine, phenylalanine, tryptophan, histidine, isoleucine — 9-10 standard).
• Non-essential: Synthesized in body (e.g., glycine, alanine, serine).

Zwitterion (Dipolar Ion): Amino acids exist as zwitterions: $H_3N^+CHR-COO^-$.

• Both ionic groups present
• High MP (like salt)
• Soluble in water; insoluble in organic solvents

Isoelectric Point (pI): pH at which amino acid exists as zwitterion (net charge = 0). Doesn't migrate in electric field at this pH.

pI depends on amino acid:

• Neutral aa's: pI ~5.5-6.5
• Acidic aa's: pI low (2.7-3.2)
• Basic aa's: pI high (8-10)

Peptide Bond: Amide bond ($-CO-NH-$) formed by reaction of $-COOH$ of one aa with $-NH_2$ of another (with loss of $H_2O$).

$H_2NCHRCOOH + H_2NCHR'COOH \to H_2NCHRC(O)-NHCHR'COOH + H_2O$

Peptides (chain of aa's via peptide bonds):

• Dipeptide: 2 aa
• Tripeptide: 3 aa
• Oligopeptide: 4-10 aa
• Polypeptide: 10-100 aa
• Protein: >100 aa typically

Protein Structure (4 Levels):

Primary Structure: Sequence of amino acids in peptide chain (held by peptide bonds).

Secondary Structure: Local 3D arrangement.

• α-helix: Spiral; stabilized by intra-chain H-bonds (between C=O of one aa and N-H of fourth aa down). Found in keratin, hemoglobin, myoglobin.
• β-pleated sheet: Side-by-side polypeptide strands held by inter-chain H-bonds. Found in silk fibroin.

Tertiary Structure: Overall 3D folding of polypeptide. Held by:

• Disulfide bonds (-S-S- between cysteine residues)
• H-bonds (within secondary structure)
• Hydrophobic interactions (non-polar R groups cluster inside)
• Electrostatic (between + and - charged R groups)
• Van der Waals

Quaternary Structure: Multiple polypeptide chains aggregating (e.g., hemoglobin has 4 chains; insulin has 2).

Types of Proteins:

Denaturation of Proteins:

• Loss of secondary/tertiary/quaternary structure (primary intact)
• Causes: heat, strong acid/base, organic solvents, urea, mechanical stress
• Examples: boiling egg (albumin denatures); milk curdling

Identification of Amino Acids:

• Ninhydrin test: purple color (or blue-violet) — used in TLC/paper chromatography
• Xanthoproteic test: yellow color with conc. HNO₃ (for aromatic side chains like Phe, Tyr, Trp)
• Biuret test: Violet color with copper sulfate in alkali (for proteins/peptides only, not aa's)

Nucleic Acids: Carriers of genetic information. Two types: DNA and RNA.

Building Blocks: Nucleotides. Each nucleotide has 3 parts:

1. Pentose sugar (deoxyribose in DNA; ribose in RNA)
2. Nitrogenous base (purine or pyrimidine)
3. Phosphate group ($PO_4^{3-}$)

Nucleoside = sugar + base. Nucleotide = sugar + base + phosphate.

Bases:

Purines (2 fused rings):

• Adenine (A)
• Guanine (G)

Pyrimidines (1 ring):

• Cytosine (C)
• Thymine (T) — DNA only
• Uracil (U) — RNA only

DNA (Deoxyribonucleic Acid):

• Pentose: 2-deoxyribose (no -OH at C2)
• Bases: A, G, C, T
• Two complementary strands forming double helix (Watson-Crick model, 1953)
• Strands run antiparallel (5' to 3' opposite directions)
• Base pairing (H-bonds):
• A pairs with T (2 H-bonds)
• G pairs with C (3 H-bonds)
• Strand backbone: sugar-phosphate-sugar-phosphate (phosphodiester bonds at 3' and 5' OH)
• DNA stores genetic info; passed during cell division

RNA (Ribonucleic Acid):

• Pentose: ribose (has -OH at C2)
• Bases: A, G, C, U (no T)
• Usually single-stranded (but can fold on itself)
• Base pairing: A-U (instead of A-T), G-C
• Three main types:
• mRNA (messenger): Carries info from DNA to ribosomes
• tRNA (transfer): Brings amino acids to ribosome
• rRNA (ribosomal): Component of ribosomes

Differences between DNA and RNA:

Genetic Code: Triplet of bases (codon) on mRNA codes for one amino acid.

• $4^3 = 64$ possible codons; 61 code for amino acids (some redundant); 3 are stop codons (UAA, UAG, UGA).
• Codon AUG = methionine = start codon

Replication: DNA copies itself before cell division (semi-conservative — each new DNA has one old, one new strand).

Transcription: DNA → mRNA (in nucleus).

Translation: mRNA → protein (at ribosomes).

Vitamins: Organic compounds required in small amounts for normal metabolic function. Body cannot synthesize them (or insufficient).

Classification:

Common Vitamins:

Enzymes: Biological catalysts; almost all are proteins (some RNA — ribozymes).

Properties:

• Highly specific for substrate and reaction
• Very efficient: rate increase $10^6 - 10^{20}$ times
• Work at mild conditions: body T ($37°$C), neutral pH, atmospheric pressure
• Sensitive to T, pH, inhibitors

Examples:

Hormones: Chemical messengers; secreted by endocrine glands; carried by blood to target organs.

Classification by Structure:

• Peptide/protein hormones: Insulin (51 aa), oxytocin (9 aa), vasopressin (9 aa), glucagon (29 aa), growth hormone
• Steroid hormones: Testosterone (male), estrogen (female), progesterone, cortisol, aldosterone (from cholesterol)
• Amino acid derivatives: Thyroxine (from tyrosine, contains I), adrenaline (epinephrine)

Key Examples:

Note: Diabetes mellitus is due to insufficient insulin (Type 1) or insulin resistance (Type 2); blood glucose remains high.