Overview
This lecture covers nucleic acids, the fourth major class of biological macromolecules. It explains their structure, how they are formed, and their essential roles in storing and transmitting genetic information in living organisms.
Recap of Organic Molecules
- There are four main classes of macromolecules: carbohydrates, lipids, proteins, and nucleic acids.
- Carbohydrates: Quick energy sources and structural components. Made of carbon, hydrogen, and oxygen, they exist as:
- Monosaccharides (simple sugars like glucose)
- Disaccharides (two monosaccharides joined, e.g., sucrose)
- Polysaccharides (long chains of monosaccharides)
- General formula: (CH₂O)n, where n is a whole number.
- Monomers join to form polymers through dehydration synthesis (removal of water).
- Lipids: Hydrophobic molecules including fats, oils, and steroids. Not true polymers.
- Triglycerides: Glycerol plus three fatty acids (saturated or unsaturated).
- Phospholipids: Have both hydrophilic (polar) and hydrophobic (non-polar) regions, crucial for cell membranes.
- Steroids: Characterized by a four-ring carbon structure.
- Proteins: Polymers of 20 different amino acids. The sequence and properties of amino acids, especially the R group, determine protein structure and function.
- Four levels of structure:
- Primary: Amino acid sequence
- Secondary: Alpha helices and beta sheets (hydrogen bonds)
- Tertiary: 3D folding (R group interactions)
- Quaternary: Multiple subunits (not in all proteins)
Introduction to Nucleic Acids
- Nucleic acids are polymers made of nucleotide monomers, joined by phosphodiester bonds through dehydration synthesis.
- They are fundamental for life, as they store and transmit genetic information.
Structure and Function of Nucleic Acids
- Genes, segments of DNA, contain instructions for making proteins, which determine cell function and phenotype.
- DNA is located in the nucleus and does not leave; it is transcribed into messenger RNA (mRNA).
- mRNA exits the nucleus and is translated by ribosomes in the cytoplasm to synthesize proteins.
- The central dogma of molecular biology describes the flow of genetic information:
- DNA can replicate itself.
- Transcription: DNA is used to make mRNA.
- Translation: mRNA directs protein synthesis.
Mutations and Disease (Sickle Cell Example)
- A single nucleotide change (point mutation) in DNA can alter the amino acid sequence of a protein, affecting its structure and function.
- Example: Sickle cell anemia results from a mutation that changes one amino acid (glutamic acid to valine) in hemoglobin.
- Glutamic acid is negatively charged and hydrophilic; valine is non-polar and hydrophobic.
- This change causes hemoglobin molecules to clump together, deforming red blood cells and reducing their oxygen-carrying capacity.
- The mutation in DNA leads to a change in mRNA, which then changes the protein and ultimately cell function.
Nucleotide Structure
- Each nucleotide consists of three components:
- A five-carbon (pentose) sugar: ribose (in RNA) or deoxyribose (in DNA).
- Deoxyribose lacks one oxygen atom compared to ribose (at the 2' carbon).
- A phosphate group, usually attached to the 5' carbon of the sugar, giving nucleic acids their acidic properties.
- A nitrogenous base, which stores genetic information.
- Bases are attached to the 1' carbon of the sugar.
- The 2' carbon distinguishes DNA (H group) from RNA (OH group).
- Nitrogenous bases are divided into:
- Pyrimidines: Single-ring structures (cytosine, thymine, uracil).
- Thymine is found only in DNA; uracil only in RNA.
- Purines: Double-ring structures (adenine, guanine).
- Mnemonic: "Pure As Gold" (A and G are purines).
Polymerization and Directionality
- Nucleotides are linked by phosphodiester bonds between the 3' hydroxyl group of one sugar and the 5' phosphate of the next.
- This linkage forms a sugar-phosphate backbone, with nitrogenous bases projecting outward.
- Nucleic acid strands have directionality: they grow from the 5' (phosphate) end to the 3' (hydroxyl) end.
- The numbering of sugar carbons (1' to 5') is crucial for understanding how nucleic acids are synthesized and read.
DNA Double Helix and Base Pairing
- DNA is double-stranded, forming a double helix with two antiparallel strands (one runs 5'→3', the other 3'→5').
- Complementary base pairing:
- Adenine (A) pairs with thymine (T) in DNA (or uracil (U) in RNA) via two hydrogen bonds.
- Guanine (G) pairs with cytosine (C) via three hydrogen bonds.
- Each base pair consists of one purine and one pyrimidine, maintaining a consistent width in the helix.
- The sugar-phosphate backbones form the sides of the helix, while the base pairs form the rungs.
- Hydrogen bonds between bases stabilize the double helix, but are weaker than the covalent bonds in the backbone.
- The antiparallel and complementary nature of DNA allows for accurate replication and transcription.
Comparison of DNA and RNA
- DNA:
- Sugar: deoxyribose (lacks an oxygen at the 2' carbon).
- Bases: adenine, guanine, cytosine, thymine.
- Structure: double-stranded, forms a stable double helix.
- Function: stores hereditary information, stable over long periods.
- RNA:
- Sugar: ribose (has an OH group at the 2' carbon).
- Bases: adenine, guanine, cytosine, uracil (replaces thymine).
- Structure: usually single-stranded, can form complex shapes.
- Function: involved in gene expression, carries instructions from DNA to ribosomes for protein synthesis, less stable and more reactive due to the extra oxygen.
Key Terms & Definitions
- Nucleotide: Monomer of nucleic acids, made of a sugar, phosphate group, and nitrogenous base.
- Phosphodiester Bond: Covalent bond linking nucleotides in a nucleic acid strand.
- Central Dogma: The flow of genetic information from DNA to RNA to protein.
- Antiparallel: The opposite orientation of the two DNA strands in the double helix.
- Mutation: A change in the DNA sequence that can alter protein structure and function.
Action Items / Next Steps
- Review the structure of nucleotides and be able to distinguish between DNA and RNA.
- Practice identifying base pairing rules and the directionality of nucleic acid strands.
- Complete assigned readings on nucleic acid structure and function to reinforce these concepts.