Biology Lecture Series – Key Vocabulary

Cellular Communication

• Fundamental components
  • Ligand = signaling molecule; specificity determines which cells respond.
  • Receptor = protein that binds ligand and initiates signal transduction.
  • Cellular response = physiological/biochemical change after signaling.
  • Second messenger = small intracellular molecule (e.g., cAMP, Ca²⁺) created by some membrane receptors; amplifies signal.
• Receptor categories
  • Intracellular receptors
  • Bind hydrophobic ligands able to cross membrane (e.g., steroid hormones).
  • Often function as transcription factors → gene expression changes.
  • Cell-surface (membrane) receptors
  • Transmembrane proteins; bind hydrophilic ligands that do NOT enter cell.
  • Receptor conveys information across membrane; may generate second messengers.
  • Sub-types include kinase-linked receptors (e.g., insulin receptor), G-protein coupled receptors, ion-channel receptors.
• Distance-based signaling types
  • Direct contact: surface molecules interact (e.g., immune synapse); gap junctions allow ion/metabolite movement.
  • Paracrine: local mediator acts on neighboring cells; short-lived growth factors.
  • Autocrine: cell targets itself.
  • Endocrine: hormones travel via bloodstream; long-lived, distant effects.
  • Synaptic: neurons release neurotransmitter across synapse; rapid, localized.
• Signal transduction themes
  • Modular cascades; each step offers branching, amplification, and regulation.
  • Reversible phosphorylation central: Protein kinases add P_i from ATP; phosphatases remove it.
  • Phosphorylation alters protein conformation, localization, stability, or enzymatic activity.
• Analogy: ligand-receptor binding parallels enzyme-substrate interaction—high specificity, saturable, reversible.

Energy & Metabolism

• Energy definitions
  • Energy = capacity to do work; measured as heat (calories/kilocalories).
  • Kinetic: energy of motion; Potential: stored energy (chemical, electrical, positional).
• Forms: mechanical, heat, light, sound, electrical, radioactive.
• Bioenergetics governed by thermodynamics
  • 1st Law: Energy is neither created nor destroyed; only converted; total universal energy constant.
  • 2nd Law: Every energy conversion increases entropy S; systems proceed toward disorder; conversions never 100 % efficient (heat loss).
• Free energy (Gibbs)
  • G = H - TS where H = enthalpy, T = absolute temperature, S increasing favors spontaneity.
  • Change in reaction: \Delta G = \Delta H - T\Delta S.
  • \Delta G < 0 → exergonic, spontaneous.
  • \Delta G > 0 → endergonic, non-spontaneous (requires energy input).
• Activation Energy E_a
  • Extra energy required to destabilize bonds and initiate reaction; lowered by catalysts (enzymes).

ATP – Cellular Energy Currency

• ATP structure: ribose + adenine + three phosphates; terminal phosphoanhydride bonds unstable.
• Hydrolysis: \text{ATP} + H2O \rightarrow \text{ADP} + Pi\;\; (\Delta G \approx -7.3\, \text{kcal·mol}^{-1}) releases energy to drive endergonic processes.
• ATP regenerated continuously via exergonic pathways (substrate-level & oxidative phosphorylation).

Enzymes

• Biological catalysts (mostly proteins); lower E_a, accelerate reactions; not consumed.
• Substrate binds active site—induced-fit model.
• Environmental factors: temperature, pH, ionic strength.
• Regulation
  • Competitive inhibitors: bind active site.
  • Noncompetitive/allosteric inhibitors: bind other site, alter shape.
  • Allosteric activators enhance affinity.
  • Feedback inhibition: end product inhibits earlier enzyme (metabolic control).
• Cofactors
  • Metal ions or organic coenzymes (e.g., B-vitamins, NAD⁺/FAD).
• Catalytic cycle example: sucrase cleaving sucrose → glucose + fructose.

Metabolism & Pathways

• Metabolism = sum of all cellular reactions.
  • Catabolic: break down molecules; release energy (exergonic).
  • Anabolic: synthesize molecules; consume energy (endergonic).
• Biochemical pathways: sequential enzyme steps; product of one reaction becomes substrate for next.

Cellular Respiration (Aerobic)

• Overall equation: C6H{12}O6 + 6O2 \rightarrow 6CO2 + 6H2O + \text{energy} \; (\Delta G \approx -686\, \text{kcal·mol}^{-1}).
• Electron carriers: NAD⁺ ⇌ NADH + H⁺ (accepts 2 e⁻ + H⁺); FAD ⇌ FADH₂ (accepts 2 e⁻ + 2 H⁺).
• ATP formation mechanisms
  1. Substrate-level phosphorylation (SLP): direct P_i transfer to ADP.
  2. Oxidative phosphorylation (OP): ATP synthase driven by proton gradient (chemiosmosis).

Stage 1 – Glycolysis (cytoplasm)

• 10-step pathway; glucose (6 C) → 2 × pyruvate (3 C).
• Investment: 2 ATP; Payoff: 4 ATP (net 2), 2 NADH, 2 H₂O.
• Splits into energy investment (G3P formation) and energy payoff (pyruvate, ATP generation).
• Fate of NADH/pyruvate depends on O₂ availability.
  • Aerobic: NADH oxidized in ETC; pyruvate → acetyl-CoA.
  • Anaerobic: fermentation regenerates NAD⁺ (lactate or ethanol pathways).

Stage 2 – Pyruvate Oxidation (mitochondrial matrix or prokaryotic membrane)

• Pyruvate + CoA + NAD⁺ → acetyl-CoA (2 C) + NADH + CO₂ + H⁺.
• Catalyzed by pyruvate dehydrogenase complex; links glycolysis to Krebs.

Stage 3 – Krebs (Citric Acid) Cycle (matrix)

• Acetyl-CoA (2 C) + oxaloacetate (4 C) → citrate (6 C); cycle regenerates oxaloacetate.
• Per acetyl-CoA: 3 NADH, 1 FADH₂, 1 ATP (via SLP), 2 CO₂.

Stage 4 – Electron Transport Chain & Chemiosmosis (inner mitochondrial membrane)

• Complexes I–IV pass electrons from NADH/FADH₂ to O₂ → H₂O.
• Energy released pumps H⁺ from matrix to intermembrane space (≈53 kcal·mol⁻¹ total).
• Proton-motive force drives ATP synthase; ≈28 ATP produced via OP per glucose.

Yield Summary (eukaryotes)

• Glycolysis: 2 ATP (SLP) + 2 NADH.
• Pyruvate oxidation: 2 NADH.
• Krebs: 2 ATP (SLP) + 6 NADH + 2 FADH₂.
• OP: ~26–28 ATP (using NADH/FADH₂; P/O ratios ≈ 2.5 & 1.5).
• Total ≈ 30–32 ATP per glucose (lower in eukaryotes due to NADH shuttle costs).

Regulation

• Feedback inhibition checkpoints
  • Phosphofructokinase (PFK) inhibited by ATP & citrate; activated by ADP.
  • Pyruvate dehydrogenase inhibited by NADH.
  • Citrate synthase inhibited by ATP.

Alternative Fuels

• Proteins → amino acids → deamination → intermediates (e.g., α-ketoglutarate).
• Fats → glycerol + fatty acids; β-oxidation produces acetyl-CoA + NADH + FADH₂ (6-C fatty acid yields ~20 % more ATP than glucose).
• Fat oxidation requires O₂; anaerobic fat catabolism not possible.

Photosynthesis (Brief Contrast)

• Light reactions: capture solar energy → ATP + NADPH; split H₂O → O₂.
• Calvin cycle (light-independent): uses ATP/NADPH to fix CO₂ → glucose.
• Respiration is essentially the reverse redox flow (glucose oxidation, O₂ reduction).

Cell Cycle & Mitosis

• Phases: G₁ → S → G₂ → Mitosis (M) → Cytokinesis (C).
  • Interphase = G₁ + S + G₂.
• Chromosome organization
  • Chromatin → nucleosomes (DNA wrapped around histone octamer: H2A, H2B, H3, H4).
  • During S: replication → sister chromatids joined at centromere via cohesins.
  • Kinetochore forms for spindle attachment.
• Mitosis stages
  1. Prophase: chromosomes condense; spindle forms; nuclear envelope breaks.
  2. Prometaphase: microtubules attach to kinetochores.
  3. Metaphase: chromosomes align on metaphase plate.
  4. Anaphase: cohesins degraded; sister chromatids pulled to poles.
  5. Telophase: nuclear envelopes re-form; chromosomes decondense.
• Cytokinesis
  • Animal cells: actin-myosin ring → cleavage furrow.
  • Plant cells: vesicles form cell plate.
• Cell-cycle control
  • Cyclins synthesized cyclically; activate cyclin-dependent kinases (Cdks).
  • Checkpoints:
  • G₁/S (“restriction point”): assesses size, nutrients, DNA integrity.
  • G₂/M: verifies DNA replication & integrity.
  • Spindle checkpoint (metaphase): ensures all kinetochores attached.
  • Growth factors (e.g., PDGF) activate signaling pathways (Ras/Raf/MEK/ERK) → cyclin gene expression.

Cancer Genetics

• Tumor-suppressor genes (loss-of-function → cancer)
  • p53: halts cycle, induces repair or apoptosis; mutated in ~50 % cancers.
  • Rb: regulates G₁/S transition; mutated in ~40 % cancers.
• Proto-oncogenes (gain-of-function when mutated → oncogenes)
  • Growth-factor receptors (e.g., HER2).
  • Ras GTPase (mutated in 20–30 % cancers).
  • Src kinase.

Meiosis & Sexual Reproduction

• Purpose: produce haploid gametes from diploid germ-line cells; enables genetic diversity and chromosome number constancy across generations.
• Two successive divisions (Meiosis I & II) with one DNA replication.
• Key events
  • Prophase I: homologous chromosomes undergo synapsis forming tetrads; crossing over at chiasmata (genetic recombination).
  • Metaphase I: tetrads align randomly (independent assortment).
  • Anaphase I: homologues separate; sister chromatids remain joined (reductional division).
  • Telophase I: nuclei haploid; chromosomes still duplicated.
  • Meiosis II: resembles mitosis; sister chromatids separate (equational division) → 4 unique haploid cells.
• Genetic variation sources
  • Crossing over.
  • Independent assortment (2ⁿ combinations; n = haploid number; humans: 2^{23} possibilities).
  • Random fusion of gametes at fertilization.
• Errors
  • Nondisjunction in Anaphase I or II → aneuploid gametes (e.g., trisomy 21); major cause of spontaneous abortion.

Comparative Highlights

• Mitosis vs Meiosis
  • Synapsis/crossing over absent in mitosis.
  • Mitosis produces 2 identical diploid cells; meiosis yields 4 non-identical haploid cells.
  • Chromosome alignment: individual chromosomes (mitosis) vs homologous pairs (meiosis I).

Key Equations & Numbers

• Gibbs free energy: \Delta G = \Delta H - T\Delta S
• ATP hydrolysis: \text{ATP} \rightarrow \text{ADP} + P_i \; (\Delta G \approx -7.3 \text{ kcal·mol}^{-1})
• Cellular respiration yield (eukaryote):
  • 6 CO2, 30\text{–}32\, \text{ATP}, 10\,\text{NADH}, 2\,\text{FADH}2 per glucose.
• Photosynthesis: 6 CO2 + 12H2O + \text{light} \rightarrow C6H{12}O6 + 6H2O + 6O_2.

Concept Integration & Real-World Relevance

• Phosphorylation cascades in signaling are mirrored in metabolic regulation (PFK, pyruvate dehydrogenase) and cell-cycle control (Cdk activity).
• Proton gradients drive ATP production in mitochondria and photosynthetic chloroplasts, illustrating chemiosmosis as a universal bioenergetic principle.
• Feedback mechanisms (allosteric inhibition, checkpoint arrest, p53-mediated apoptosis) underscore cellular economy and genomic integrity—disruption leads to pathologies such as cancer.