Core Principles of Cell Biology, Macromolecules, and Genetics

Cell Biology Fundamentals and Origins

Cell Theory

  • The cell is the fundamental unit of life.
  • Living organisms are comprised of cells.
  • Cells arise only from pre-existing cells.
  • All life shares a common ancestor.

Origin of Life and Water Properties

The common origin of life is estimated at 4 billion years ago (bya).

Hypotheses for the Causes of Life:

  • Primordial Soup: Early Earth conditions (gases, water, energy) led to the formation of organic molecules.
  • Miller-Urey Experiment: Demonstrated that energy reactions could create basic organic molecules from inorganic precursors.
  • Extra-terrestrial Origin: Molecules arrived via meteorites.

Evidence includes Stromatolites (3.5 bya).

Properties of Water:

Water’s unique properties stem from hydrogen bonds:

  • High specific heat.
  • Cohesion and surface tension.
  • Polarity: Makes water a solvent for hydrophilic (polar) molecules, while hydrophobic (nonpolar) molecules are excluded.

Biological Macromolecules and Chemical Bonds

  • Carbohydrates: Linked by glycosidic bonds. Examples include saccharides, starch, glycogen, and cellulose.
  • Nucleic Acids (DNA/RNA): Linked by phosphodiester bonds, formed between the 3′ hydroxyl group and the 5′ phosphate group.
  • Proteins: Linked by peptide bonds, formed between the carboxyl group of one amino acid and the amino group of another.
  • Lipids: Non-polar molecules often linked by ester bonds.
    • Saturated Fats: Straight chains, contain only single bonds (typically solid).
    • Unsaturated Fats: Contain one or more double bonds, resulting in kinks (typically liquid).

Prokaryotic Cell Structure and Classification

Bacterial Classification (Gram Staining)

  • Gram-Positive Bacteria (Gram +):
    • Possess a thick peptidoglycan cell wall.
    • Lack an outer membrane.
    • Stain purple.
    • Generally susceptible to common antibiotics.
  • Gram-Negative Bacteria (Gram -):
    • Possess a thin peptidoglycan layer.
    • Have an outer membrane.
    • Stain pink or red (counterstain).
    • Often more resistant to antibiotics due to the outer membrane.

Archaea

Archaea are distinct prokaryotes characterized by the absence of peptidoglycan in their cell walls. They often thrive in extreme environments (extremophiles).

Eukaryotic Organelle Evolution (Endosymbiosis)

  • Nucleus Origin: Formed by the infolding of the plasma membrane around the genetic material (DNA).
  • Mitochondria Origin: A result of primary endosymbiosis—the engulfment of a purple non-sulfur bacterium.
    • This established a symbiotic relationship.
    • Mitochondria retain circular DNA and bacterial ribosomes.
  • Chloroplast Origin: A result of the engulfment of a cyanobacterium.
    • Chloroplasts contain their own DNA (similar to cyanobacteria) and are surrounded by a double membrane.

Cellular Architecture and Transport Systems

The Cytoskeleton

The cytoskeleton provides structure, movement, and transport within the cell. It consists of three main components:

  1. Microfilaments (Actin): Maintains cell shape, facilitates cell movement, and is crucial for cytokinesis (cell division).
  2. Intermediate Filaments (Keratin): Provides mechanical strength, anchors organelles, and resists tension.
  3. Microtubules (Tubulin): Acts as tracks for organelle transport, forms the mitotic spindle, and constitutes the core of cilia and flagella.

The Secretory Pathway

This system processes, modifies, and transports proteins and lipids:

  1. Rough Endoplasmic Reticulum (RER): Site of protein synthesis and folding.
  2. Smooth Endoplasmic Reticulum (SER): Site of lipid and steroid synthesis, detoxification, and calcium storage.
  3. Golgi Apparatus: Modifies proteins, sorts, and packages materials for delivery.
  4. Vesicles: Transport materials (e.g., secretory vesicles, lysosomes, endosomes).
  5. Plasma Membrane: Final destination for secreted or membrane-bound components.

Genetics, DNA Replication, and Cell Cycle Control

Eukaryotic DNA Replication

  1. Initiation: Helicase unwinds the double helix; Primase lays down RNA primers.
  2. Elongation:
    • Leading Strand: Synthesized continuously in the 5′ to 3′ direction.
    • Lagging Strand: Synthesized discontinuously, forming Okazaki fragments, which are sealed by Ligase.
  3. Termination: Replication forks meet and merge.

The Cell Cycle

Interphase (Growth and Preparation)

  • G1 Phase: Cell growth; contains the Restriction Checkpoint.
  • S Phase: DNA replication occurs, resulting in two sister chromatids.
  • G2 Phase: Final growth and checks; contains the G2 Checkpoint (ensures readiness for mitosis).

M Phase (Mitosis and Cytokinesis)

  1. Prophase: Chromosomes become visible; the mitotic spindle begins forming; centrosomes migrate to poles.
  2. Prometaphase: Nuclear envelope breaks down; spindle fibers attach to kinetochores.
  3. Metaphase: Chromosomes align at the metaphase plate; the Spindle Checkpoint ensures proper kinetochore attachment.
  4. Anaphase: Sister chromatids separate and move toward opposite poles.
  5. Telophase: Chromosomes decondense; the spindle disassembles; new nuclear envelopes form.
  6. Cytokinesis: Division of the cytoplasm.

Cell Cycle Regulation (CDKs)

Cyclin-Dependent Kinases (CDKs) control the cell cycle by phosphorylating target proteins. CDKs are only active when bound to regulatory proteins called cyclins.

G1-S Transition Control: The RB protein normally blocks progression. The G1/S Cyclin-CDK complex phosphorylates RB, leading to its inactivation, allowing the cell to proceed into the S phase.

Bioenergetics and Fundamental Thermodynamics

Laws of Thermodynamics in Biology

  • First Law of Thermodynamics: Energy cannot be created or destroyed; it can only be transferred or transformed from one form to another.
  • Second Law of Thermodynamics: In any energy transfer, the total entropy (disorder) of a closed system always increases over time.

ATP Hydrolysis (Energy Currency)

ATP hydrolysis is the primary energy-releasing reaction in the cell:

ATP + H₂O → ADP + Pᵢ + Energy

  • This reaction is exergonic (releases energy, resulting in a negative Gibbs free energy change).
  • Energy is released primarily due to the breakage of the high-energy bond between the second and third phosphate groups.