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Citric Acid Cycle Steps with Structures

    In this citric acid cycle steps with structures post we have briefly explained about citric acid cycle pathway Background, definition, citric acid cycle pathway steps with structures, and Energetics.

    Citric Acid Cycle Pathway

    Sir Hans Adolf Krebs, a German-born British scientist, invented this citric acid cycle pathway, which he termed the citric acid cycle pathway, in 1937. He was awarded the Nobel Prize in Physiology or Medicine in 1953 for his achievements. Despite the fact that Krebs explained the majority of the reactions in this route, his design had some flaws. The discovery of coenzyme A by Fritz Lipmann and Nathan Kaplan in 1945 allowed researchers to devise the modern-day reaction cycle.

    Background

    In eukaryotes and prokaryotes, the citric acid cycle pathway is the most prevalent mechanism of oxidative breakdown. The mitochondria are involved in this process. The citric acid cycle pathway, commonly known as the Krebs cycle, is the fundamental engine of cellular respiration.

    It is responsible for the majority of glucose, fatty acid, and amino acid oxidation, as well as the production of numerous biosynthetic precursors.

    The citric acid cycle pathway is amphibolic, meaning it works in both catabolic and anabolic modes. The citric acid cycle pathway, unlike glycolysis, is a cyclic process. i.e., the pathway’s last reaction regenerates the molecule that was used in the initial reaction. The citric acid cycle pathway only produces one GTP molecule (ATP equivalent) and does not use oxygen directly.

    Reactions

    The citric acid cycle pathway starts with acetyl CoA generated by the oxidation of pyruvate (derived from glucose and other catabolic processes) and harvests much of its bond energy in the form of NADH, FADH2, and GTP molecules through a number of events.

    The citric acid cycle pathway reduced electron carriers, NADH and FADH2, will transmit their electrons onto the electron transport chain, resulting in oxidative phosphorylation, which will create the majority of the ATP produced in cellular respiration.

    Prior to the start of the first step, a transitional phase occurs during which pyruvate is converted to acetyl CoA. This process occurs in the mitochondrial matrix and provides a link between the glycolysis and the citric acid cycle pathway which consists the following eight steps.

    TCA Cycle

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    Step 1

    In the first step of the citric acid cycle pathway, the acetyl CoA (two-carbon) reacts with a oxaloacetate molecule (four-carbon) to form citrate (six-carbon) in a condensation reaction.

    This reaction is catalysed by the enzyme citrate synthase. The CoA is bound to a thiol group (-SH) and diffuses away to eventually combine with another acetyl group.

    This step is irreversible because it is highly exergonic. The rate of this reaction is controlled by negative feedback and the amount of ATP available. If ATP levels increase, the rate of this reaction decreases. If ATP is in short supply, the rate increases.

    Step 2

    In second step citrate is converted into its isomer, isocitrate, by the enzyme aconitase.

    Step 3

    In the third step, the isocitrate is oxidized, to produce a five-carbon molecule, α-ketoglutarate releasing a molecule of CO2. In this process two electrons are also released which reduce a NAD+ molecule to NADH. This step is catalysed by isocitrate dehydrogenase.

    Step 4

    In the step four, α-ketoglutarate is oxidised to succinyl CoA a four carbon molecule in the presence of Coenzyme A. In this step also a NAD+ molecule is reduced to NADH. This reaction is catalysed by α-ketoglutarate dehydrogenase enzyme

    TCA Cycle

    Citric Acid Cycle Pathway

    Citric Acid Cycle Pathway

    Step 5

    In step five, the succinyl CoA is converted into succinate with the release of large amount of energy. This energy is utilised for the phosphorylation of a guanine diphosphate (GDP) to guanine triphosphate (GTP) by the addition of inorganic phosphate.

    GTP is energetically equivalent to ATP; it is primarily used in protein synthesis, however, its use is more restricted. This reaction is catalysed by the enzyme, succinyl-CoA synthetase.

    Step 6

    Step six is a dehydration process that converts succinate into fumarate. Two hydrogen atoms are transferred to FAD, producing FADH2.

    Unlike NADH, this carrier remains attached to the enzyme succinate dehydrogenase which catalyses this reaction, and transfers the electrons to the electron transport chain directly.

    Step 7

    Water is added to fumarate in step seven, and malate is produced. This reaction is catalysed by fumarase.

    Step 8

    The last step of the citric acid cycle pathway regenerates oxaloacetate by oxidizing malate. Another molecule of NADH is produced in this reaction, which is catalysed by malate dehydrogenase.

    Energetics of Citric Acid Cycle Pathway

    Through the electron transport chain, each NADH will eventually create 2.5 ATP and each FADH 2 will make 1.5 ATP, resulting in a total ATP production of 10 ATP from 1 acetyl CoA.

    Two molecules of CO2 are released

    Three molecules of NADH is generated

    One molecule of FADH2 is generated

    One molecule of GTP is produced.

    TCA Cycle

    Energetics of Citric Acid Cycle Pathway

    Further Readings

    Reference