Biological Macromolecules Notes (Markdown)

Carbohydrates

• Macromolecule class: Carbohydrates; Monomers: monosaccharides; Polymers: polysaccharides (e.g., starch, glycogen, cellulose, chitin, peptidoglycan).
• General chemical formula: $C<em>nH</em>{2n}O<em>n\quad (n=3\text{ to }7)$. Example: glucose is $C</em>6H<em>{12}O</em>6$.
• Monomer diversity:
  • Number of carbons (triose, pentose, hexose, etc.).
  • Location of the carbonyl group (aldose vs ketose).
  • Structural isomers: same formula, different bonding patterns; ring form vs linear form (in solution). Example: glucose exists in linear and ring forms.
• Monosaccharide structure and linkage:
  • Monosaccharides bond to form polymers via dehydration/condensation reactions, releasing water: $\text{Monomer}<em>1 + \text{Monomer}</em>2 \rightarrow \text{Polymer} + \mathrm{H_2O}$.
  • Polysaccharides are joined by glycosidic linkages (bond between monomers).
  • The type of glycosidic linkage (alpha vs beta) and the specific carbons connected (e.g., 1,4 linkage) determine polymer properties.
• Glycosidic linkages: alpha vs beta
  • Example linkages: $\alpha\text{-1,4-glycosidic linkage}$ and $\beta\text{-1,4-glycosidic linkage}$.
  • Function depends on linkage type: energy storage (alpha) vs structural support (beta).
• Energy storage polysaccharides:
  • Plants store sugar as starch (a mix of amylose and amylopectin).
  • Animals store sugar as glycogen.
  • Bond type for energy storage: primarily alpha glycosidic linkages; these are more readily hydrolyzed to release glucose.
• Structural polysaccharides:
  • Cellulose (plant/algal cell walls): parallel strands connected by hydrogen bonds; beta linkages confer rigidity.
  • Chitin (fungal cell walls and insect exoskeletons): parallel strands connected by hydrogen bonds.
  • Peptidoglycan (bacterial cell walls): monomers modified with amino acids; parallel strands connected by peptide bonds.
• Other roles:
  • Components of larger molecules: polysaccharides part of glycoproteins, glycolipids, and involvement in DNA/RNA components.
  • Cell identity: surface carbohydrate structures contribute to cell recognition.
• Structure–function relationship:
  • The ring form, stereochemistry, and glycosidic linkage type directly influence digestibility, branching, and physical properties (solubility, rigidity).
• Key takeaways:
  • Carbohydrates serve as energy sources, structural materials, and molecular identifiers in cells.

Lipids

• Core functions:
  • Energy storage (fats and oils) for animals and plants.
  • Cushioning and insulation in animals.
  • Major component of cell membranes (phospholipid bilayer).
  • Precursors for vitamins (e.g., Vitamin D3) and sterols such as cholesterol and hormones.
• Major lipid types:
  • Triglycerides (fats and oils): glycerol backbone with three fatty acids.
  • Phospholipids: form lipid bilayers in membranes; amphipathic molecules with a polar head and nonpolar tails.
  • Sterols: cholesterol and steroid hormones (e.g., testosterone, estradiol, cortisol).
• Fats structure and properties:
  • Fats are triacylglycerols: triglycerides formed from glycerol plus three fatty acids.
  • Saturation varies:
  • Saturated fats: only single C–C bonds; typically solid at room temperature.
  • Unsaturated fats: contain one or more C=C bonds; typically liquid at room temperature.
  • Physical state influenced by chain length and degree of saturation; longer chains and higher saturation favor solids (e.g., butter), whereas shorter or unsaturated chains favor liquids (e.g., vegetable oil).
• Hydrogenation:
  • Process converting unsaturated fats to saturated fats by adding H2 to break C=C bonds; increases shelf-life and melting point but can have health risks.
• Membrane lipids:
  • Phospholipids are amphipathic: hydrophilic head groups face water; hydrophobic tails face inward, forming the bilayer.
  • This dynamic bilayer supports membrane structure and function.
• Steroids:
  • Four-ring structure; include cholesterol and steroid hormones; cholesterol is an important membrane component and a precursor for steroid hormones and bile acids.
• Practical implications:
  • Lipid composition affects membrane fluidity and function; hydrogenation and dietary fats influence health.

Proteins

• What they are:
  • Polymers of amino acids linked by peptide bonds.
  • 20 naturally occurring amino acids with the same core structure: a central carbon (alpha carbon), a hydrogen, an amino group (—NH2), a carboxyl group (—COOH), and a distinctive side chain (R-group).
• Amino acid ionization (in aqueous solution, pH ~7):
  • The amino group can accept a proton to become (\text{NH}_3^+).
  • The carboxyl group can lose a proton to become (\text{COO}^-).
  • In solution, amino acids ionize to optimize solubility and reactivity.
• R-groups (side chains) determine properties:
  • Categories: nonpolar (hydrophobic); polar uncharged; polar positively charged; polar negatively charged.
  • Physical/chemical behavior and interactions are determined by side chains.
• Peptide bonds and polypeptides:
  • Formation is a condensation reaction between the carboxyl group of one amino acid and the amino group of another, releasing water:
  • $\text{Amino}<em>{1}-COOH + \text{NH}</em>2 - \text{Amino}<em>{2} \rightarrow \text{Amino}</em>{1}-CO-NH-\text{Amino}<em>{2} + \mathrm{H</em>2O}$
• N-terminus and C-terminus:
  • Each amino acid chain has an N-terminus (amino end) and a C-terminus (carboxyl end).
  • The polypeptide backbone is the same, while side chains project outward.
• Protein structure and function:
  • Function is determined by 3D shape (structure dictates activity).
  • Four levels of structure:
  • Primary: amino acid sequence encoded by the gene.
  • Secondary: hydrogen bonds in the backbone form alpha helices (a-helix) or beta sheets (b-pleated sheets).
  • Tertiary: overall 3D folding driven by side-chain interactions (hydrogen bonds, hydrophobic interactions, Van der Waals, ionic bonds, and covalent disulfide bonds).
  • Quaternary: assembly of multiple polypeptide subunits into a functional protein.
• Protein folding and quality control:
  • Folding is often spontaneous because folded state is energetically favored.
  • Molecular chaperones assist proper folding in cells.
  • Unfolded or misfolded proteins can cause disease if not degraded.
• Denaturation:
  • Denaturation is unfolding of a protein, destroying its 3D structure.
  • Reversible denaturation: changes in salt concentration or pH can denature/renature proteins.
  • Irreversible denaturation: heating, radiation, or physical disruption can permanently unfold proteins.
• Misfolding and disease:
  • Prions are abnormally folded forms of normal prion proteins; can induce misfolding in normal proteins and propagate disease.
  • Prion diseases include Kuru, Creutzfeldt–Jakob Disease (CJD), Bovine Spongiform Encephalopathy (BSE, mad cow disease), Scrapie, and Chronic Wasting Disease (CWD).
  • Prions cause neurodegeneration through accumulation of misfolded protein aggregates.
• GFP as a model example:
  • Green Fluorescent Protein (GFP) from jellyfish used as a biomarker when expressed in other organisms.
  • GFP is a beta-barrel-shaped protein with a fluorescent chromophore at its center.
• Contemporary tools:
  • AI-based structure prediction (e.g., AlphaFold) enables prediction of protein folding and interactions, aiding understanding of health and disease.
• Miscellaneous:
  • The sequence of amino acids encodes the structural information; folding leads to function.
  • Mutations alter sequence, potentially altering structure and function, with possible physiological consequences.

Nucleic Acids

• Core idea:
  • DNA and RNA store and transmit genetic information; both are polymers of nucleotides.
• Nucleotides: components and structure
  • A nucleotide has three components:
  • A phosphate group
  • A five-carbon sugar (ribose in RNA; deoxyribose in DNA)
  • A nitrogenous base (purine or pyrimidine)
  • In DNA/RNA, the sugar’s C5 is bonded to the phosphate; the C1 is bonded to the nitrogenous base.
  • Sugar differences:
  • RNA uses ribose (C2'–OH present).
  • DNA uses deoxyribose (lacks the 2'-OH; has H instead).
  • Nucleotides link via phosphodiester bonds: the 5' phosphate of one nucleotide links to the 3' hydroxyl of the next.
• Sugar differences and bases:
  • Nucleobases: Purines (A, G) and Pyrimidines (C, T, U).
  • In RNA, uracil (U) replaces thymine (T).
• Primary structure and directionality:
  • Nucleic acids are read/written in the 5' to 3' direction.
  • A nucleotide sequence represents the primary structure.
• Nucleic acid polymerization:
  • Nucleotides polymerize to form RNA (ribonucleotides) and DNA (deoxyribonucleotides).
  • Condensation reaction with phosphodiester linkages releases water.
• Chargaff’s rules (DNA composition):
  • In any DNA sample, purines equal pyrimidines: $A+G = C+T.$
  • Also, $A = T\quad\text{and}\quad G = C.$
  • Example problem: If a bacterial DNA has 20% T, then A% = 20% and the rest (C and G) sum to 60%; individual values must satisfy A=T and G=C.
• The DNA double helix (structure and pairing):
  • Rosalind Franklin, Maurice Wilkins, Watson, and Crick established the double-helix structure.
  • Two antiparallel strands form the double helix with a hydrophilic sugar–phosphate backbone on the exterior and nitrogenous bases inside.
  • Base pairing:
  • A pairs with T via 2 hydrogen bonds.
  • G pairs with C via 3 hydrogen bonds.
  • The double helix is the secondary structure of DNA.
• Levels of DNA structure:
  • Primary: sequence of nucleotides.
  • Secondary: double helix.
  • Tertiary: 3D folding/bending of the DNA molecule.
  • Quaternary: interaction of DNA with proteins or RNAs.
• RNA structure and function:
  • RNA differs from DNA in:
  • Uracil replaces thymine.
  • Ribose sugar (with 2′-OH).
  • RNA is typically single-stranded, allowing it to fold into various secondary structures (hairpins, stems, loops).
  • RNA secondary structure forms via intramolecular base pairing (within the same strand).
  • RNA tertiary structure supports 3D shapes (e.g., tRNA).
  • Functions of RNA types:
  • mRNA: carries instructions for protein synthesis.
  • tRNA: delivers amino acids during translation.
  • rRNA: component of the ribosome and protein synthesis machinery.
  • microRNAs and other functional RNAs regulate gene expression and catalysis.
  • Ribozymes: RNA molecules with catalytic activity.
• RNA world and catalytic RNA:
  • RNA can function both as a repository of genetic information and as a catalyst (ribozymes), suggesting an ancient RNA world prior to DNA/protein dominance.
• The ribosome and RNA–protein interactions (quaternary):
  • Ribosome is a complex where RNA and proteins interact to synthesize proteins; RNAs can have catalytic roles and structural roles within ribosomes.
• AI and structure prediction (context):
  • Advances like AlphaFold enhance our ability to predict folding and interactions of proteins, including complexes with DNA/RNA and ligands.

Nucleic Acids (Continued: RNA vs DNA in function and structure)

• Function and diversity:
  • DNA stores genetic information; RNA transmits and translates information to build proteins.
  • The information content is encoded in sequence; base pairing rules enable accurate replication and transcription.

Protein Folding and Misfolding: Implications and Tools

• Proper folding is essential for function; misfolded proteins can cause disease.
• Molecular chaperones assist folding and prevent aggregation.
• Denaturation can be reversible or irreversible depending on the cause.
• Prions demonstrate how misfolded proteins can propagate misfolding and cause neurodegenerative diseases.
• AI and computational tools (e.g., AlphaFold) help predict protein structure and interactions, accelerating research and understanding of health and disease.

Connections to Real-World Relevance

• Structure determines function across macromolecules: sequence → structure → function.
• Misfolding and aggregation underlie several diseases (e.g., prion diseases).
• Understanding carbohydrate linkages informs nutrition and digestion (digestibility of starch/glycogen vs cellulose/chitin).
• Lipid composition affects membrane properties, signaling, and health (e.g., hydrogenation consequences).
• AI-driven structure prediction (AlphaFold) accelerates drug design, understanding of diseases, and exploration of protein interactions.

Quick Reference: Key Equations and Notation

• Dehydration/condensation polymerization (general):
  • $\text{Monomer}<em>1 + \text{Monomer}</em>2 \rightarrow \text{Polymer} + \mathrm{H_2O}$
• Hydrolysis (reverse):
  • $\text{Polymer} + \mathrm{H<em>2O} \rightarrow \text{Monomer}</em>1 + \text{Monomer}_2$
• Peptide bond formation (condensation between amino and carboxyl groups):
  • $\text{AA}<em>1{-}COOH + \text{H}</em>2N{-}\text{AA}<em>2 \rightarrow \text{AA}</em>1{-}CO{−}NH{-}\text{AA}<em>2 + \mathrm{H</em>2O}$
• Carbohydrate formula and example:
  • $C<em>nH</em>{2n}O_n\quad (3 \le n \le 7)$
  • Glucose: $\text{C}<em>{6}\text{H}</em>{12}\text{O}_{6}$
• Glycosidic linkages:
  • $\alpha{-}1{,}4{-}glycosidic\; linkage$
  • $\beta{-}1{,}4{-}glycosidic\; linkage$
• Nucleotides and nucleic acids:
  • Nucleotide components: phosphate, sugar, base.
  • Phosphodiester bond (5' to 3' linkage):
  • $5'{-}\text{phosphate} - 3'{-}\text{OH} \quad (\text{condensation})$
• Chargaff's rules (DNA composition):
  • $A + G = C + T\quad\text{and}\quad A = T,\; G = C$
• DNA base pairing: A–T (2 H-bonds), G–C (3 H-bonds).
• RNA vs DNA sugar and bases: Uracil (U) in RNA; Thymine (T) in DNA; Ribose in RNA; Deoxyribose in DNA.