Cell Membranes and Lipid Bilayers

Chapter 11 – Cell Membranes

The Lipid Bilayer

• Lipid bilayers are formed due to the amphipathic nature of phospholipids.
• They feature hydrophilic heads and hydrophobic tails.
• Phospholipids spontaneously form double layers in water to shield hydrophobic tails.
• The bilayer is a fluid mosaic, allowing lateral protein movement.
• This fluidity aids cell signaling, transport, and flexibility.
• Bilayer fluidity is affected by fatty acid saturation (more saturated = less fluid) and cholesterol.
• Cholesterol stabilizes and modulates fluidity.
• Membrane assembly begins in the endoplasmic reticulum (ER).
• Enzymes insert newly made lipids into the cytosolic side of the ER membrane.
• Enzymes like flippases cause certain phospholipids to be confined to one side.
• This creates membrane asymmetry, which is important for signaling and vesicle formation.

Membrane Proteins

• Integral proteins span the membrane (transmembrane).
• Peripheral proteins attach to the membrane surface.
• Lipid-anchored proteins are covalently bound to lipids.
• Alpha helices stabilize in the hydrophobic core and hide polar backbone elements, making them common in membrane proteins.
• The cell cortex is a mesh of proteins (like actin) under the plasma membrane.
• It provides strength, shape, and aids in movement.
• Cells can restrict protein movement by tethering to the cytoskeleton or extracellular structures.
• Tight junctions block diffusion between regions.
• This is used for cell polarity and function compartmentalization.
• Membranes are coated with carbohydrates.
• Glycoproteins and glycolipids form a glycocalyx.
• The glycocalyx is involved in cell-cell recognition, protection, and adhesion.

Chapter 12 – Transport Across Cell Membranes and Electrical Signaling

Transmembrane Transport Principles

• Small nonpolar molecules (O₂, CO₂) pass freely across membranes.
• Small uncharged polar molecules (H₂O, ethanol) are somewhat permeable.
• Large polar or charged molecules (ions, glucose) need transport proteins to cross membranes.
• Typical ion concentrations inside vs. outside cells: Na⁺ is high outside, K⁺ is high inside, and Ca²⁺ is very low inside.
• Ion gradients allow electrical signals, transport, and homeostasis.
• Membrane potential is the voltage difference across the membrane due to ion imbalance.
• It is used in nerve signals, muscle contraction, and transport.
• Transporters bind specific solutes, change shape, and are slower.
• Channels are selective pores that allow ions to flow quickly.
• Channels are often gated (voltage, ligand, or mechanical).
• Passive transport occurs with the gradient and requires no energy.
• Active transport occurs against the gradient and needs energy (ATP or ion gradient).
• The concentration gradient and membrane potential together form the electrochemical gradient.
• If one force pushes an ion in and the other pushes it out, net flow depends on which is stronger.
• Water moves from low solute to high solute (down its gradient) during osmosis.
• Water moves into cells in hypotonic environments and out in hypertonic environments.

Transporters & Their Functions

• Electrochemical gradient defines passive transporters.
• For example, glucose transporters, selective based on shape/charge.
• Active transport (pumps) uses ATP or ion gradients.
• It is needed to maintain cell volume, ion gradients, and membrane potential.
• Na⁺/K⁺ pump pumps 3 Na⁺ out and 2 K⁺ in.
• It is powered by ATP.
• This maintains electrochemical gradient and prevents cell swelling.
• Ca²⁺ pumps keep cytosolic Ca²⁺ very low.
• This is important for muscle contraction and signaling.
• Coupled pumps use Na⁺ or H⁺ gradients to move other solutes.
• Symport involves both in the same direction (e.g., Na⁺/glucose).
• Antiport involves opposite directions.
• Plant, fungal, and bacterial pumps use H⁺ gradients, not Na⁺, for coupled transport.

Ion Channels & Membrane Potential

• Selectivity filters in ion channels are based on size and charge.
• Gating responds to voltage, ligands, or mechanical force.
• Membrane potential is governed by permeability, dominated by K⁺ permeability at rest.
• Ion channels snap open/closed randomly, but probability changes with stimuli.
• Stimuli types include voltage-gated (respond to charge), ligand-gated (respond to chemical signals), and mechanically-gated (respond to stretch or pressure).

Ion Channels & Nerve Signaling

• An action potential is a rapid change in membrane potential down the axon.
• It allows fast communication in neurons.
• Voltage-gated channels generate action potentials.
• Na⁺ channels open, Na⁺ enters, causing depolarization.
• K⁺ channels open later, K⁺ exits, causing repolarization.
• Voltage-gated Ca²⁺ channels at the synapse open when the signal arrives.
• Ca²⁺ enters, triggering neurotransmitter release.
• Transmitter-gated ion channels are on the postsynaptic membrane.
• Neurotransmitter binds, the channel opens, and the signal continues.
• Excitatory neurotransmitters open Na⁺ or Ca²⁺ channels, causing depolarization.
• Inhibitory neurotransmitters open Cl⁻ or K⁺ channels, causing hyperpolarization.

Chapter 13 – How Cells Harvest Energy from Food

Three Major Stages of Food Breakdown

• Digestion, outside cells, involves large food molecules becoming smaller subunits (amino acids, sugars, fatty acids).
• It occurs in the gut and lysosomes.
• Glycolysis in the cytosol converts glucose into 2 pyruvate + ATP + NADH.
• No oxygen is needed.
• Oxidation in mitochondria converts pyruvate into CO₂ + H₂O.
• It produces lots of ATP via oxidative phosphorylation.

Glycolysis (in cytosol)

• Inputs: Glucose, 2 ATP, 2 NAD⁺.
• Outputs: 2 Pyruvate, 4 ATP (net = 2), 2 NADH.
• Steps: energy investment (2 ATP used); splitting glucose into 2 3-carbon sugars; energy payoff (4 ATP + 2 NADH produced).

Fermentation (no oxygen)

• Purpose: regenerate NAD⁺ so glycolysis can continue.
• Lactic acid fermentation (humans): pyruvate → lactate.
• Alcohol fermentation (yeast): pyruvate → ethanol + CO₂.
• Only 2 ATP/glucose, far less efficient than aerobic respiration.

Acetyl-CoA Formation

• Occurs in the mitochondrial matrix.
• Pyruvate → Acetyl-CoA + CO₂ + NADH.
• Fatty acids and some amino acids can also form Acetyl-CoA.

Citric Acid Cycle (Krebs cycle)

• Location: mitochondrial matrix.
• Inputs: Acetyl-CoA.
• Outputs (per Acetyl-CoA): 3 NADH, 1 FADH₂, 1 GTP (→ATP), 2 CO₂.
• Steps: Acetyl-CoA (2C) joins oxaloacetate (4C) → citrate (6C); Series of oxidation steps → regenerate oxaloacetate.

Activated Carriers

• Main carriers: NADH, FADH₂.
• Carry high-energy electrons to the electron transport chain (ETC).
• Their energy is used to pump protons and make ATP.

ATP Synthesis

• The ETC uses NADH/FADH₂ to create an H⁺ gradient across the inner mitochondrial membrane.
• ATP synthase uses the gradient to make ~28 ATP per glucose.

Regulation of Metabolism

• Feedback regulation controls energy use.
• High ATP slows glycolysis and the citric acid cycle.
• Low ATP speeds them up.
• Enzymes like phosphofructokinase are key control points.
• Metabolism switches between breakdown (catabolism) and biosynthesis (anabolism) based on cell needs.

Chapter 8 – The Cell Cycle and Apoptosis

Basics of the Cell Cycle

• Phases: Interphase: G₁ (growth), S (DNA synthesis), G₂ (prep for mitosis); M phase: Mitosis + cytokinesis; G₀ phase: Resting or non-dividing state.
• Checkpoints ensure accuracy: G₁/S checkpoint: is the environment favorable?; G₂/M checkpoint: is all DNA replicated and undamaged?; Metaphase checkpoint: are chromosomes attached to the spindle?

Cyclins & CDKs

• Cyclins are regulatory proteins that fluctuate in concentration.
• CDKs (Cyclin-dependent kinases) are enzymes activated by cyclins.
• Cyclin-CDK complexes push the cell through the cycle.
• G₁/S cyclin-CDK commits cells to division.
• S cyclin-CDK initiates DNA replication.
• M cyclin-CDK starts mitosis.

Cell Cycle Regulation

• Controlled by phosphorylation (activation/inhibition of CDKs), proteolysis (cyclin degradation to exit phases), and CDK inhibitors (like p21).
• Mitogens stimulate division by overcoming inhibitory proteins.
• For example, Rb protein inhibits transcription factors; mitogens inactivate Rb.
• DNA damage triggers p53, which activates p21, which inhibits CDKs, halting the cycle.

DNA Replication

• Occurs during S phase.
• Requires origin recognition, helicase loading, and licensing.
• Controlled by S-CDK; replication must happen only once per cycle.

M Phase (Mitosis)

• Prophase: chromosomes condense, the spindle forms.
• Prometaphase: nuclear envelope breaks, chromosomes attach.
• Metaphase: chromosomes line up.
• Anaphase: sister chromatids separate.
• Telophase: nuclear envelope reforms.
• Cytokinesis: cell divides.
• M-CDK triggers mitosis; APC/C degrades proteins to exit mitosis.

Apoptosis (Programmed Cell Death)

• Normal, controlled cell death to remove unwanted/damaged cells.
• Key players: caspases (proteases that break down cell contents).
• Intrinsic pathway: triggered by damage or stress; mitochondria release cytochrome c; activates apoptosome; caspases.
• Extrinsic pathway: triggered by death ligands (e.g., Fas) binding to receptors; caspase cascade.