Cellular metabolic pathways

Introduction

  • Primary Energy Source: ATP (Adenosine Triphosphate)

    1. Why ATP?

      • ATP contains high-energy phosphate bonds. When a phosphate group is removed (forming ADP and a free phosphate), energy is released, which powers cellular processes.

  • Two Methods of ATP Production:

    1. Substrate-Level Phosphorylation

      • ATP is produced directly by adding a phosphate group to ADP.

      • How? A phosphate group is transferred from a phosphorylated substrate (a bound Pi) to ADP.

      • Examples: Glycolysis, the Krebs cycle, and creatine phosphate.

    2. Oxidative Phosphorylation

      • Energy is used to attach an inorganic, unbound phosphate (Pi) to ADP, forming ATP.

      • Example: Electron Transport Chain (ETC).

Glycolysis

  • Definition: Breakdown (catabolism) of carbohydrates or sugars.

  • Location: Occurs in the cytosol through a series of 10 reactions.

  • Net Production: 2 ATP molecules per glucose molecule.

    • If Oxygen (O₂) is Present (Aerobic):

      • NADH is produced, which acts as an electron carrier (often referred to as a "pickup truck" for electrons).

      • Pyruvate is the end product, which enters the Krebs cycle for further energy production.

    • If Oxygen is Absent (Anaerobic):

      • An additional (11th) reaction occurs, leading to the production of lactate (lactic acid).

      • Oxygen is not required, but the energy yield remains low, producing just 2 ATP.

      • Note: This process allows cells to generate energy in low-oxygen environments.

  • Regulation: The process is regulated by the levels of ATP and ADP. High ATP levels inhibit glycolysis, while high ADP levels stimulate it.

Krebs Cycle (Citric Acid Cycle)

  • Definition: Further breakdown (catabolism) of pyruvate.

    • Alternative sources: Some amino acids and lipids can also enter the Krebs cycle.

  • Location: Takes place in the mitochondria through 8 reactions.

  • Net Production: 2 ATP molecules, along with byproducts such as CO₂, NADH, and FADH₂.

    • NADH and FADH₂: These are electron carriers used in the electron transport chain (ETC) for oxidative phosphorylation.

    • Dependence on Oxygen: Indirectly dependent on oxygen because the electron transport chain needs oxygen to function properly.

  • Regulation: The cycle is controlled by the concentrations of ATP and ADP.

Electron Transport System/Chain (ETC/ETS)

  • Primary Function: Acts as the final destination for NADH and FADH2, where these electron carriers unload their high-energy electrons.

  • Location: Occurs in the inner membrane of the mitochondria.

  • Net Product: Generates between 28-34 ATP molecules per glucose molecule, water (H2O) as a byproduct, and recycles NAD+ and FAD for further use in cellular respiration.

  • Dependence on Oxygen: Oxygen is the final electron acceptor, making this process directly aerobic. Without O2, the ETC halts, stopping ATP production.

  • Oxidative Phosphorylation: The process involves oxidation of NADH/FADH2 and phosphorylation of ADP to ATP using energy released by the electron flow.

  • Additional Mitochondrial Role: The mitochondria can also retain some ATP for performing other cellular functions and metabolic processes.

Transport Across the Plasma Membrane

  • Plasma Membrane (PM) as a Discriminant Barrier:

    • The PM acts as a selective barrier, controlling what enters and exits the cell.

  • Structure of the Plasma Membrane:

    • Lipid Bilayer: Composed of two layers of phospholipids.

      • Hydrophobic Interactions: The bilayer is stabilized by hydrophobic (water-repelling) bonds between the fatty acid tails of phospholipids.

      • Tail Regions: The hydrophobic tails face inward, creating a barrier that restricts the movement of polar substances.

  • Permeability:

    • Nonpolar Compounds: Small nonpolar molecules (e.g., oxygen, carbon dioxide) can diffuse through the lipid bilayer because they are not repelled by the hydrophobic interior.

    • Polar and Larger Compounds: The bilayer is less permeable to polar molecules (e.g., water, ions) and larger molecules, which require special mechanisms to cross.

  • Transport Proteins:

    • Channels: Proteins that form pores in the membrane, allowing specific ions or molecules to pass through.

    • Transporters (Carriers): Proteins that bind to specific molecules and change shape to transport them across the membrane.

  • Vesicular Transport:

    • Vesicles: Membrane-bound sacs that facilitate the transport of large molecules or particles into and out of the cell through processes like endocytosis and exocytosis.

Diffusion Basics

  • Requirements for Diffusion:

    • Random Motion: Molecules move randomly due to thermal energy.

    • Concentration Gradient: The difference in concentration of a substance between two areas, affecting the movement of molecules.

      • Formula: Concentration [x] = Amount of x / Volume (v).

  • Direction of Diffusion:

    • Molecules move from areas of high concentration to areas of low concentration.

  • Factors Affecting Diffusion:

    • Permeability: How easily molecules can pass through the membrane.

    • Surface Area: Larger surface areas allow more molecules to diffuse.

    • Concentration Gradient: Greater differences in concentration increase the rate of diffusion.

    • Distance: Longer distances can slow down diffusion and limit efficiency.


Diffusion Through the Bilayer

  • With Gradient:

    • Diffusion occurs along the concentration gradient (from high to low concentration) without requiring energy input.

  • Energy Costs:

    • Passive Transport: Diffusion through the lipid bilayer is a passive process, meaning it does not require energy.

  • Limitations:

    • Permeability to Small Nonpolar Molecules: While the PM is permeable to small nonpolar molecules, this doesn’t allow for storage of such molecules.

    • Solutions to Limitations:

      • Adjust the concentration gradient to optimize diffusion.

      • Utilize transport proteins to facilitate movement of polar and larger molecules.

Diffusion Through Protein/Ion Channels

  • General Characteristics:

    • With Gradient: Movement through protein or ion channels occurs along the concentration gradient without the need for energy (passive transport).

    • Solute Specific: Each channel is specific to certain ions or molecules, allowing only those particular substances to pass through.

  • Types of Channels:

    • Leak Channels: These are always open, allowing continuous flow of ions or molecules.

    • Gated Channels: Open or close in response to specific signals or conditions.

      • Voltage-Gated Channels: Open or close in response to changes in membrane potential (electrical distribution).

      • Mechanically Gated Channels: Open or close in response to mechanical pressure or stretching of the membrane.

      • Thermally Gated Channels: Open or close in response to temperature changes.

  • Aquaporins:

    • Special channels that facilitate the diffusion of water molecules through the membrane by osmosis.


Osmosis

  • Definition:

  • Osmosis: The net movement of water molecules across a semipermeable membrane from an area of lower solute concentration to an area of higher solute concentration.

  • Concentration Effects:

    • Water Concentration: Inversely related to solute concentration. As solute concentration increases, water concentration decreases.

  • Osmolarity:

    • Definition: The total concentration of solutes in a solution.

    • Relation to Water Concentration: Higher osmolarity means lower water concentration.

Consequences of Osmosis

  • Change in Cell Size:

    • Isotonic Solution: The concentration of nonpolar solutes is the same inside and outside the cell. There is no net movement of water, so the cell size remains constant.

    • Hypertonic Solution: Higher concentration of nonpolar solutes outside the cell. Water moves out of the cell, causing it to shrink.

    • Hypotonic Solution: Lower concentration of nonpolar solutes outside the cell. Water moves into the cell, causing it to swell and possibly burst.

  • Osmotic Pressure:

    • Definition: The pressure required to stop the net flow of water across a semipermeable membrane.

    • Requirements:

      • Semipermeable Membrane: Allows some substances (nonpolar solutes) to pass through but not others.

      • Immobile Solute: The volume of the solution must remain constant to measure osmotic pressure accurately.

    • Effect of Osmotic Pressure: An increase in osmotic difference (osmolarity) increases osmotic pressure.

    • Biological Relevance: The immune system utilizes osmotic gradients to remove unwanted cells.


Carrier-Mediated Transport

  • Basics:

    • Function: Proteins act as carriers or shuttles to transport molecules across the membrane.

    • Regulation: Binding of molecules to the carrier protein regulates the transport process.

  • Types of Transporters:

    • Facilitated Diffusion: Movement of molecules down their concentration gradient with the help of carrier proteins, without energy input.

    • Active Transport: Movement of molecules against their concentration gradient, requiring energy (usually from ATP).

  • Facilitated Diffusion:

    • With Gradient: Does not require energy as it occurs along the concentration gradient.

    • Conformational Changes: Carrier proteins undergo shape changes to transport molecules across the membrane.

    • Saturation: Occurs when the transport proteins are fully occupied by molecules, leading to a maximum rate of transport.

    • Competition: Different molecules can compete for the same transporter.

Example: Glucose transporter proteins facilitate the uptake of glucose into cells.