The Krebs Cycle, also known as the Citric Acid Cycle or Tricarboxylic Acid (TCA) cycle, is a fundamental metabolic pathway occurring within the cells of most living organisms. This process takes place in the mitochondrial matrix of eukaryotic cells, playing a central role in cellular respiration. Its primary function involves the breakdown of fuel molecules, such as acetyl-CoA derived from carbohydrates, fats, and proteins, to generate energy. The cycle prepares molecules for further energy production, making it an indispensable part of how cells produce the energy needed for various functions.
Key Electron Carriers: NADH and FADH2
A significant output of the Krebs Cycle is the production of electron carriers, specifically Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FADH2). These molecules are crucial for capturing the high-energy electrons released during the breakdown of carbon compounds within the cycle. NADH and FADH2 do not directly provide usable energy in the form of ATP; instead, they function as energy shuttles, transporting these energetic electrons to the next stage of cellular respiration.
For each molecule of acetyl-CoA that enters the Krebs Cycle, three molecules of NADH and one molecule of FADH2 are typically produced. These carriers are generated at specific points in the cycle through oxidation reactions, where NAD+ is reduced to NADH and FAD is reduced to FADH2. The electrons carried by NADH and FADH2 represent a substantial portion of the energy harvested from the initial fuel molecules, setting the stage for the cell’s main energy payoff.
Directly Produced Energy: ATP and GTP
While the majority of energy from the Krebs Cycle is captured indirectly by electron carriers, the cycle does produce a small amount of direct energy in the form of Adenosine Triphosphate (ATP) or Guanosine Triphosphate (GTP). For each turn of the cycle, one molecule of ATP or GTP is generated. This direct energy production occurs through a process called substrate-level phosphorylation.
In substrate-level phosphorylation, a phosphate group is directly transferred from a high-energy substrate molecule to Adenosine Diphosphate (ADP) to form ATP, or to Guanosine Diphosphate (GDP) to form GTP. GTP is functionally equivalent to ATP in terms of energy transfer and can be readily converted to ATP by an enzyme called nucleoside diphosphate kinase. This direct energy yield, though modest compared to the subsequent stages of respiration, provides immediate cellular energy.
Carbon Dioxide: A Byproduct
The Krebs Cycle also produces carbon dioxide (CO2) as a byproduct. This CO2 represents the complete oxidation of the carbon atoms that entered the cycle from the original fuel molecules.
Specifically, two molecules of CO2 are released for every molecule of acetyl-CoA that completes one turn of the Krebs Cycle. This carbon dioxide is considered a waste product of cellular respiration and is ultimately exhaled by organisms. The release of CO2 signifies the successful breakdown of the carbon skeleton of the fuel molecules.
Fueling the Powerhouse: How Krebs Cycle Products Drive Energy Production
The significance of the Krebs Cycle’s electron carrier products, NADH and FADH2, becomes apparent in the final stages of aerobic cellular respiration: the Electron Transport Chain (ETC) and oxidative phosphorylation. These high-energy electron carriers, along with those from glycolysis, transport their captured electrons to the ETC, located in the inner mitochondrial membrane. Here, the electrons are passed along a series of protein complexes, releasing energy gradually at each step.
This controlled release of energy powers the pumping of protons (hydrogen ions) from the mitochondrial matrix into the intermembrane space, creating a proton gradient. The accumulation of protons in the intermembrane space creates an electrochemical potential difference across the membrane. This gradient then drives protons back into the mitochondrial matrix through an enzyme called ATP synthase. The flow of protons through ATP synthase fuels the synthesis of a large amount of ATP from ADP and inorganic phosphate, a process known as oxidative phosphorylation. Oxygen serves as the final electron acceptor, combining with electrons and protons to form water. This process, where the energy stored in NADH and FADH2 is converted into ATP, highlights the role of the Krebs Cycle as a preparatory stage for cellular energy production.