ATP & Brain function

• ATP (Adenosine Triphosphate)


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


  Known as the "energy currency" of the cell due to its role in storing and transferring energy
• ATP


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


  ADP+Pi+Free Energy→ATP
• ΔG for ATP Synthesis

  +50 kJ/mol (endergonic, requires energy input)
• ATP Hydrolysis


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

  • 50 kJ/mol (exergonic, releases energy)
• Conditions for Reverse ATP Synthase Activity

  • High ATP concentration
  • Low H⁺ concentration in the outer membrane
• Importance of ATP hydrolysis in the brain

  Provides the energy required for various cellular processes in the brain, including ion transport and neurotransmitter cycling
• Glucose is the main energy source for the brain
• Processes for brain energy production: Glycolysis, citric acid cycle, and oxidative phosphorylation
• The brain has a high level of oxygen consumption due to the demands of oxidative phosphorylation
• The brain's daily ATP requirement is 100-150 moles (equivalent to 50-75 kg)
• Each ADP molecule is recycled 1000 to 1500 times per day to meet the brain's ATP demand
• The brain is ~2% of body weight but consumes ~15% of cardiac output, ~20% of total body oxygen, and ~25% of total body glucose
• The brain is the most energy-demanding organ relative to its size, consuming a disproportionate amount of the body's resources
• Active K⁺ Transport


  Na⁺/K⁺ ATPase pumps Na⁺ out of and K⁺ into neurons, maintaining the electrochemical gradients essential for action potentials
• The Na⁺/K⁺ ATPase hydrolyzes ATP to provide the energy for these ion transport processes
• The Na⁺/K⁺ ATPase is essential for maintaining the resting membrane potential and enabling the propagation of action potentials
• Glutamate Signaling


  Glutamate binds to glutamate receptors on the postsynaptic membrane, causing ion channels to open and leading to depolarization of the neuron
• Glutamate is taken up by astrocytes and converted to glutamine, a process that requires ATP
• Efficient removal and recycling of glutamate prevent excitotoxicity and maintain synaptic function
• Coupled Reactions: Phosphorylation of glucose during glycolysis

  Glucose+ATP→Glucose-6-phosphate+ADP
• Mechanism of coupled reactions

  ATP hydrolysis provides the necessary energy to drive the phosphorylation of glucose, which is an otherwise energetically unfavorable reaction
• The total daily ATP use in the human body is approximately 100-150 moles, equivalent to 50-75 kg
• ADP is continually converted back to ATP, maintaining the high turnover rate necessary for cellular functions
• Shrews have an extremely high metabolic rate, consuming 200-300% of their body weight in food daily
• Humans allocate around 25% of metabolic energy to brain function
• The brain's high ATP consumption is critical for sustaining complex functions such as cognition, memory, and sensory processing
• The development of a larger, more complex human brain was facilitated by efficient ATP production through oxidative phosphorylation
• The brain's high energy requirement makes it particularly sensitive to disruptions in energy supply, such as hypoxia (low oxygen levels)
• ATP hydrolysis drives the conformational changes in the Na⁺/K⁺ ATPase enzyme, enabling ion transport
• ATP is required for the conversion of glutamate to glutamine in astrocytes, which is then transported back to neurons
• The Na⁺/K⁺ ATPase converts the chemical energy from ATP hydrolysis into mechanical work, pumping ions against their gradients
• ATP binding and hydrolysis induce changes in the Na⁺/K⁺ ATPase enzyme's structure, altering its affinity for Na⁺ and K⁺ ions and enabling transport
• ATP in the brain drives critical processes like ion transport and neurotransmitter recycling, and supports the high metabolic demands of neuronal activity
• ADP recycling is 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 our advanced cognitive capabilities