The final two reactions of the citric acid cycle involve the conversion of fumarate to malate and then malate to oxaloacetate. The first reaction, where fumarate is converted to L-malate, has a delta G close to zero, indicating that it is reversible under biological conditions. This reaction involves the addition of water, which can be simplified as a single step but actually occurs in two parts: first, hydroxide ion (OH-) is added, followed by a proton (H+), resulting in the reduction of a double bond and the formation of an alcohol group.
In the subsequent step, malate is oxidized to oxaloacetate by the enzyme malate dehydrogenase, which has a positive delta G of approximately 30 kJ/mol. However, under physiological conditions, this reaction also approaches a delta G of zero, making it reversible. This step produces NADH, a crucial electron carrier in cellular respiration.
When considering ATP production, each NADH generated can yield approximately 2.5 ATP during oxidative phosphorylation, while FADH2 yields about 1.5 ATP. The variability in ATP yield from NADH is due to its entry point in the electron transport chain, which can affect the total ATP produced from glucose metabolism. Overall, one glucose molecule can yield between 30 to 32 ATP, accounting for the contributions from glycolysis, pyruvate oxidation, and the citric acid cycle.
In terms of ATP accounting, glycolysis contributes 5 to 7 ATP, with a net gain of 2 ATP after considering the consumption of ATP during the process. Pyruvate oxidation contributes an additional 5 ATP from the generation of NADH, while the citric acid cycle produces 20 ATP from the oxidation of 2 acetyl CoA molecules, resulting in a significant energy yield from aerobic respiration compared to glycolysis alone.
The regulation of the citric acid cycle is primarily influenced by the energy status of the cell, with energy-rich molecules like ATP and NADH acting as inhibitors, while energy-poor molecules such as AMP, ADP, and NAD+ stimulate the cycle. Key enzymes, including pyruvate dehydrogenase and those involved in the citric acid cycle, are regulated by feedback mechanisms where the products inhibit the enzymes, preventing overproduction, while substrates stimulate them, indicating a need for more energy production.
Additionally, anaplerotic reactions play a vital role in replenishing intermediates of the citric acid cycle, such as oxaloacetate, which can be diverted for biosynthetic processes, including amino acid synthesis. These reactions ensure that the cycle can maintain its function and output, especially when intermediates are drawn off for other metabolic pathways. The ability to reverse certain reactions within the cycle allows for flexibility in metabolic processes, ensuring that essential molecules are available when needed.
