Energy Transfer System and ATP

• The energy transfer system is the final common pathway of energy metabolism, which is the process by which the body obtains and uses energy from food.

Overview of energy transfer

• The system harnesses the chemical energy of macronutrients (carbohydrates, fats, and proteins) to generate adenosine triphosphate (ATP).
• ATP is the primary energy currency of the cell, powering various biological processes, including muscle contraction, nerve impulse transmission, and biosynthesis.
• The energy transfer system involves a series of biochemical reactions that occur in the mitochondria of cells.
• These reactions can be broadly divided into three main stages:
  • Generation of Acetyl-CoA
  • Citric Acid Cycle (Krebs Cycle)
  • Electron Transport Chain (ETC) or Oxidative Phosphorylation

Generation of Acetyl-CoA

• Acetyl-CoA is a central molecule in metabolism, linking glycolysis and fatty acid oxidation to the citric acid cycle.
• Pyruvate, the end product of glycolysis, which is the breakdown of glucose, is converted to acetyl-CoA through oxidative decarboxylation, catalyzed by the pyruvate dehydrogenase complex.
• Fatty acids undergo beta-oxidation in the mitochondria, which involves the sequential removal of two-carbon units in the form of acetyl-CoA.
• Amino acids can also be converted to acetyl-CoA or other intermediates that enter the citric acid cycle.

Citric Acid Cycle (Krebs Cycle)

• Acetyl-CoA enters the citric acid cycle by combining with oxaloacetate to form citrate.
• Through a series of enzymatic reactions, citrate is oxidized, releasing carbon dioxide (CO2) and generating high-energy electron carriers: NADH and FADH2.
• The citric acid cycle also produces a small amount of ATP (or GTP) through substrate-level phosphorylation.
• The primary function of the citric acid cycle is to generate high-energy electron carriers (NADH and FADH2) for the electron transport chain.

Electron Transport Chain (ETC) or Oxidative Phosphorylation

• NADH and FADH2 donate electrons to the electron transport chain, a series of protein complexes embedded in the inner mitochondrial membrane.
• As electrons are passed along the chain, they release energy, which is used to pump protons (H+) from the mitochondrial matrix into the intermembrane space, creating an electrochemical gradient.
• The flow of protons back into the matrix through ATP synthase drives the synthesis of ATP from ADP and inorganic phosphate (Pi).
• This process is known as oxidative phosphorylation, as it couples the oxidation of NADH and FADH2 to the phosphorylation of ADP.
• Oxygen (O2) is the final electron acceptor in the electron transport chain, combining with electrons and protons to form water (H2O).

ATP Production

• ATP production varies depending on the substrate being oxidized.
• Complete oxidation of one molecule of glucose yields a net of 30-32 ATP molecules.
• Fatty acids yield more ATP per carbon atom than glucose due to their higher degree of reduction.
• The efficiency of ATP production is influenced by factors such as the availability of oxygen and the integrity of the mitochondrial membrane.

Regulation of Energy Transfer

• The energy transfer system is tightly regulated to meet the energy demands of the cell and the body.
• Allosteric regulation of key enzymes in glycolysis, the citric acid cycle, and the electron transport chain.
• Availability of substrates, such as glucose, fatty acids, and oxygen.
• Hormonal control, including insulin, glucagon, and epinephrine.
• Cellular energy charge (ATP/ADP ratio).

Efficiency of Energy Transfer

• Not all the energy released from the oxidation of substrates is captured as ATP.
• Some energy is lost as heat, which contributes to body temperature regulation.
• The efficiency of oxidative phosphorylation is influenced by factors such as proton leak across the mitochondrial membrane and the activity of uncoupling proteins (UCPs).
• UCPs dissipate the proton gradient, reducing ATP production but increasing heat generation.

Importance of Oxygen

• Oxygen is essential for efficient energy production in the electron transport chain.
• Under anaerobic conditions, the electron transport chain is inhibited, and ATP production is limited to glycolysis.
• Anaerobic glycolysis results in the production of lactate, which can lead to muscle fatigue and acidosis.

Mitochondrial Function

• Mitochondria play a central role in energy metabolism and are also involved in other cellular processes, such as apoptosis and calcium homeostasis.
• Mitochondrial dysfunction is implicated in various diseases, including neurodegenerative disorders, cardiovascular disease, and cancer.

Key enzymes in the energy transfer system

• Pyruvate dehydrogenase complex (PDH)
• Citrate synthase
• Isocitrate dehydrogenase
• α-ketoglutarate dehydrogenase complex
• Succinate dehydrogenase
• ATP synthase

Inhibitors of the electron transport chain

• Rotenone
• Antimycin A
• Cyanide
• Carbon monoxide
• Oligomycin