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Cellular Energetics, Endomembrane System & Trafficking, and Signal Transduction: Study Notes

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Cellular Energetics

Metabolic Pathways: Anabolic vs. Catabolic

Metabolic pathways are series of chemical reactions occurring within a cell. They are classified as either anabolic (building up) or catabolic (breaking down) pathways.

  • Anabolic Pathways: Synthesize complex molecules from simpler ones; require energy input (endergonic).

  • Catabolic Pathways: Break down complex molecules into simpler ones; release energy (exergonic).

  • Example: Protein synthesis (anabolic); glycolysis (catabolic).

Types of Organisms by Oxygen Requirement

  • Aerobic Organisms: Require oxygen for survival; use oxygen as the final electron acceptor in respiration.

  • Anaerobic Organisms: Live without oxygen; use alternative electron acceptors or fermentation.

  • Facultative Organisms: Can survive with or without oxygen, switching metabolic pathways as needed.

Glucose Catabolism: Overview and ATP Yield

Glucose catabolism involves several stages, each localized to specific cellular compartments and generating ATP and electron carriers.

  • Glycolysis: Occurs in the cytosol; breaks down glucose into two pyruvate molecules, producing 2 ATP and 2 NADH.

  • Fate of Pyruvate: Depends on oxygen availability:

    • Anaerobic: Fermentation (lactate or ethanol + CO2 pathways).

    • Aerobic: Pyruvate oxidation (mitochondrial matrix) → Citric Acid Cycle (mitochondrial matrix) → Oxidative Phosphorylation (inner mitochondrial membrane).

  • ATP Yield: Total ATP from aerobic glucose catabolism is typically 30-32 ATP per glucose molecule.

Summary Table: ATP Yield by Stage

Stage

Location

ATP Produced

Electron Carriers

Glycolysis

Cytosol

2 (net)

2 NADH

Pyruvate Oxidation

Mitochondrial Matrix

0

2 NADH

Citric Acid Cycle

Mitochondrial Matrix

2

6 NADH, 2 FADH2

Oxidative Phosphorylation

Inner Mitochondrial Membrane

~26-28

Uses all NADH/FADH2

Fermentation Pathways

  • Lactate Fermentation: Pyruvate is reduced to lactate; occurs in muscle cells under low oxygen.

  • Ethanol Fermentation: Pyruvate is converted to ethanol and CO2; occurs in yeast.

Aerobic Respiration: Key Steps

  • Pyruvate Oxidation: Pyruvate → Acetyl-CoA + CO2 + NADH.

  • Citric Acid Cycle (Krebs Cycle): Acetyl-CoA is oxidized, generating NADH, FADH2, and GTP/ATP.

  • Oxidative Phosphorylation: Electron carriers donate electrons to the electron transport chain (ETC); chemiosmosis drives ATP synthesis via the proton motive force.

Key Equation:

Catabolism of Fatty Acids and Proteins

  • Fatty Acid Catabolism (β-oxidation): Fatty acids are broken down in the mitochondrial matrix to generate acetyl-CoA, NADH, and FADH2.

  • Protein Catabolism: Proteins are hydrolyzed to amino acids, which are deaminated and converted into intermediates of glycolysis or the citric acid cycle.

Endomembrane System and Trafficking

Components, Morphology, and Functions

  • Endoplasmic Reticulum (ER):

    • Rough ER: Studded with ribosomes; site of protein synthesis and initial glycosylation.

    • Smooth ER: Lacks ribosomes; involved in lipid synthesis, drug detoxification, carbohydrate metabolism, calcium storage, and steroid biosynthesis.

  • Golgi Apparatus: Consists of cis (entry) and trans (exit) faces; modifies, sorts, and packages proteins and lipids for delivery.

  • Lysosomes: Acidic organelles containing hydrolytic enzymes; degrade macromolecules and originate from endosomes.

Trafficking Between Endomembrane Compartments

  • Vesicular Transport: Proteins and biomolecules are transported in vesicles between compartments.

  • Directionality:

    • Anterograde: ER → Golgi → Plasma membrane/lysosome.

    • Retrograde: Plasma membrane/Golgi → ER.

Protein Import and Sorting

  • Cotranslational Import: Proteins enter the ER during translation, guided by a signal sequence, signal recognition particle (SRP), and translocon.

  • Integral Membrane Proteins: Use stop-transfer and start-transfer sequences to embed in the membrane.

  • Posttranslational Import: Some proteins are imported into organelles after translation.

  • Sorting Signals: Retention and retrieval tags (amino acid sequences, hydrophobic region length, covalent modifications) direct proteins to their correct locations.

Exocytosis and Endocytosis

  • Exocytosis: Process by which vesicles fuse with the plasma membrane to secrete contents; includes constitutive and regulated secretion.

  • Endocytosis: Uptake of materials into the cell via vesicle formation.

    • Types: Phagocytosis, pinocytosis, and receptor-mediated endocytosis.

    • Receptor-Mediated Endocytosis: Involves clathrin, adaptor proteins, and dynamin; specific uptake of ligands via receptors.

    • Fates of Endocytosed Ligands/Receptors: Recycling, degradation, or transcytosis.

Coated Vesicles: Types and Directionality

Coat Protein

Direction

Main Function

Clathrin

Plasma membrane ↔ Endosomes/Golgi

Endocytosis, vesicle formation

COPI

Golgi → ER (retrograde)

Retrieval of escaped ER proteins

COPII

ER → Golgi (anterograde)

Transport of newly synthesized proteins

SNARE-Mediated Membrane Fusion

  • v-SNAREs: Located on vesicles; interact with t-SNAREs on target membranes.

  • t-SNAREs: Located on target membranes; ensure specificity of fusion.

  • Tethering Proteins and Rab GTPases: Mediate initial vesicle docking.

  • NSF and SNAPs: Disassemble SNARE complexes after fusion.

  • Steps: Tethering → Docking → Fusion → Disassembly.

Signal Transduction: Electrical and Synaptic Mechanisms

Cell Types in the Nervous System

  • Neurons: Specialized for signal transmission; include sensory, motor, and interneurons.

  • Glial Cells: Support neurons; types include microglia (immune), oligodendrocytes (CNS myelination), Schwann cells (PNS myelination), and astrocytes (support and nutrient supply).

Neuron Morphology and Function

  • Cell Body (Soma): Contains nucleus and organelles.

  • Dendrites: Receive signals from other neurons.

  • Axon: Conducts electrical impulses away from the cell body.

  • Synapse: Junction between neurons for signal transmission.

Membrane Potential and Ion Movement

  • Resting Potential: The stable, negative charge of a neuron at rest (typically -70 mV).

  • Action Potential: Rapid change in membrane potential due to Na+ influx (depolarization) and K+ efflux (repolarization and hyperpolarization).

  • Phases: Depolarizing, repolarizing, and hyperpolarizing.

Key Equation (Nernst Equation):

Electrical Signal Transmission

  • Nonmyelinated Axons: Action potential propagates continuously along the axon.

  • Myelinated Axons: Action potential jumps between nodes of Ranvier (saltatory conduction), increasing speed.

Synaptic Transmission

  • Chemical Synapses: Neurotransmitters are released from presynaptic neuron and bind to receptors on postsynaptic neuron.

  • Electrical Synapses: Direct passage of ions via gap junctions.

  • Neurotransmitter Secretion and Uptake: Exocytosis of neurotransmitters; reuptake or enzymatic degradation terminates the signal.

Example: Acetylcholine is released at neuromuscular junctions, triggering muscle contraction.

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