ATP & brain function

• ATP (Adenosine Triphosphate)


  Composed of adenine (a nitrogenous base), ribose (a five-carbon sugar), and three phosphate groups
• Energy Carrier


  Known as the "energy currency" of the cell due to its role in storing and transferring energy
• Unstable High-Energy Bonds


  • The bonds between the phosphate groups are high-energy bonds due to electrostatic repulsion between the negatively charged phosphate groups
• ATP Hydrolysis


  ATP+H2O→ADP+Pi+Free Energy
• ΔG for ATP Hydrolysis

  • 50 kJ/mol, indicating a release of free energy
• Conditions for Reverse Rotation

  • High ATP concentration
  • Low H⁺ concentration in the outer membrane
• The human brain requires 100-150 moles of ATP daily
• 150 moles of ATP = 9×10259×1025 ATP molecules
• ATP molecular weight: 507 g/mol
• ATP needed in a single day: 50 to 75 kg
• The human body uses a vast amount of ATP daily due to its non-spontaneous biological processes, which require significant energy expenditure
• Each ADP molecule is recycled 1000 to 1500 times daily to meet ATP demands
• Glucose is the primary energy source for the brain, converted to ATP through glycolysis and oxidative phosphorylation
• The brain's high-maintenance nature increases its vulnerability to disruptions in energy supply
• If energy supply is cut off for even 10 minutes, it can lead to permanent brain damage
• Humans allocate a higher percentage of metabolic energy to brain function compared to other animals
• Energy Allocation


  • Shrews: ~3% of energy to the brain
  • Dogs/Wolves: ~4-5%
  • Apes: ~8%
  • Humans: ~25%
• Active K⁺ Transport


  1. Na⁺/K⁺ ATPase: Pumps Na⁺ out of and K⁺ into neurons, maintaining the electrochemical gradients essential for action potentials

  2. ATP hydrolysis drives conformational changes in the enzyme, allowing ion transport

  3. Binding: Na⁺ binds to the enzyme from the cytoplasmic side

  4. Phosphorylation: ATP is hydrolyzed, and the enzyme is phosphorylated

  5. Conformational Change: Phosphorylation causes a conformational change, releasing Na⁺ outside the cell

  6. K⁺ Binding: K⁺ binds to the enzyme from the extracellular side

  7. Dephosphorylation: The enzyme is dephosphorylated, reverting to its original conformation, and K⁺ is released inside the cell
• Free Energy Utilization


  Free energy from ATP hydrolysis drives the firing of signals along neurons
• Glutamate Signaling


  • Glutamate is the main excitatory neurotransmitter in the brain
  • Glutamate binds to receptors on the postsynaptic neuron, opening cation channels and depolarizing the membrane
  • Recycling: Glutamate is converted to glutamine in astrocytes, requiring ATP
  • Importance: Prevents excitotoxicity by clearing glutamate from the synaptic cleft, allowing for proper neuronal signaling and preventing overstimulation
• Coupled Reactions


  1. Example: Phosphorylation of glucose during glycolysis

  2. Glucose+ATP→Glucose-6-phosphate+ADP

  3. ATP hydrolysis provides the necessary energy to drive endergonic reactions, facilitating metabolic processes
• Cells avoid making ATP from scratch by recycling ADP into ATP, similar to the recycling of intermediates in the citric acid cycle
• Efficient ATP production through oxidative phosphorylation facilitated the development of larger, more complex brains
• Increased brain size and energy requirements impose severe risks during evolution, such as vulnerability to energy supply disruptions
• ATP in the Brain: Drives critical processes like ion transport and neurotransmitter recycling, Supports high metabolic demands of neuronal activity
• ADP Recycling: Essential to sustain the high ATP turnover required by brain functions
• ATP hydrolysis converts chemical energy into conformational work necessary for cellular activities
• Human brain metabolism is uniquely high, reflecting advanced cognitive capabilities and evolutionary adaptations