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Citric acid cycle
The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a central component of cellular respiration. It plays a key role in the metabolic pathway where cells generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into carbon dioxide and a chemical called ATP (adenosine triphosphate).
Overview of the cycle
The cycle begins with the condensation of acetyl-CoA with oxaloacetate to form citrate, catalyzed by an enzyme called citrate synthase. This reaction is important because it controls the flow of carbon through the cycle.
oxaloacetate + acetyl-CoA → citrate + CoA
The citrate molecule undergoes isomerization process to form isocitrate, which is catalyzed by aconitase. It involves a hydration step followed by a dehydration step.
Citrate ⇌ Isocitrate
Decarboxylation and energy production
It then undergoes oxidative decarboxylation by isocitrate dehydrogenase to form α-ketoglutarate, producing NADH and releasing CO2.
Isocitrate + NAD + → α-ketoglutarate + NADH + H + + CO 2
α-Ketoglutarate undergoes another oxidative decarboxylation to form succinyl-CoA, catalyzed by the α-ketoglutarate dehydrogenase complex. This step also forms NADH and CO2.
α-Ketoglutarate + NAD + + CoA → Succinyl-CoA + NADH + H + + CO 2
Regeneration of oxaloacetate
The cycle continues with the conversion of succinyl-CoA to succinate, catalyzed by succinyl-CoA synthetase, and is coupled to the phosphorylation of GDP to GTP (which can subsequently form ATP).
Succinyl-CoA + GDP + PI → Succinate + CoA + GTP
Succinate then undergoes oxidation to form fumarate through the action of succinate dehydrogenase, which is also involved in the electron transport chain. This step generates FADH2.
Succinate + FAD → fumarate + FADH2
The conversion of fumarate to malate is catalyzed by fumarase, which adds water to the double bond.
fumarate + H 2 O → malate
Finally, malate is oxidized by malate dehydrogenase, regenerating oxaloacetate, producing NADH.
Malate + NAD + → Oxaloacetate + NADH + H +
Energetic yield
In the oxidation of one acetyl-CoA molecule by the citric acid cycle, the major reduced cofactors are produced: three NADH, one FADH2, and one GTP (or ATP). Each NADH can be converted by the electron transport chain into about 2.5 molecules of ATP, and each FADH2 into about 1.5 molecules of ATP.
Regulation of the cycle
The citric acid cycle is strictly regulated through allosteric regulation of key enzymes. These include citrate synthase, isocitrate dehydrogenase, and the α-ketoglutarate dehydrogenase complex. High levels of ATP and NADH indicate a high-energy state of the cell and inhibit these enzymes, while high levels of ADP and NAD + indicate a low-energy state and activate the enzymes.
Importance in metabolism
Beyond energy production, the citric acid cycle provides several metabolic intermediates needed for various biosynthetic pathways. For example, α-ketoglutarate and oxaloacetate are important for amino acid synthesis. In addition, succinyl-CoA is important for heme synthesis.
Scene summary
The integration of the cycle with other metabolic pathways highlights its central role.
Conclusion
The citric acid cycle is an important aerobic pathway for energy production in cells. It not only generates ATP and other energy molecules to fuel cellular activities, but also contributes to various anabolic processes by providing building blocks for macromolecules. Its efficiency and regulation are essential for the proper functioning of living organisms.