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The Citric Acid Cycle

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The citric acid cycle is a closed loop of reactions that occur in the mitochondrial matrix, including redox, dehydration, hydration, and decarboxylation reactions.

It's name is derived from the intermediate compound citric acid as the steps were first described by Hans Krebs, this aerobic pathway is also known as the Krebs cycle, which over a series of eight enzymatic steps, is critical in glucose catabolism.

To begin, acetyl CoA, the resulting compound from pyruvate oxidation donates its acetal group to a four carbon molecule oxaloacetate forming a six carbon intermediate citrate. While it's CoA group is bound to a self hydro group and diffused away to eventually combine with another acetal group. A water molecule is then removed and replaced, transforming citrate into its isomer isocitrate. The molecule is then oxidized, reducing NAD+ to NADH and H+, and a carbon dioxide molecule, forming a five carbon alpha-ketoglutarate.

This product releases another carbon dioxide molecule and two electrons, reducing another NAD+ to NADH and a proton. Leaving the molecule with an unstable bond, where a coenzyme A attaches forming succinyl CoA. In the next step, the coenzyme is replaced by a phosphate group. Then the phosphate is transferred to GDP forming succinate and GTP, which can be used to generate ATP.

During step six, succinate is oxidized with two electrons from hydrogen atoms, transformed to the electron carrier flavin adenine dinucleotide, FAD to produce FADH2 and fumarate. Water is then added to the resulting molecule and after bond rearrangement forms into malate.

Finally this molecule is oxidized, reducing NAD+ to NADH and H+, regenerating the original compound, oxaloacetate. In the end, each cycle produces three NADH and one FADH2. High energy electron carriers that are used in the electron transport chain.

Overview

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The citric acid cycle, also known as the Krebs cycle or TCA cycle, consists of several energy-generating reactions that yield one ATP molecule, three NADH molecules, one FADH₂ molecule, and two CO₂ molecules.

Acetyl CoA is the point-of-entry into the citric acid cycle, which occurs in the inner membrane (i.e., matrix) of mitochondria in eukaryotic cells or the cytoplasm of prokaryotic cells. Prior to the citric acid cycle, pyruvate oxidation produced two acetyl CoA molecules per glucose molecule. Hence, the citric acid cycle runs twice per glucose molecule.

The citric acid cycle can be partitioned into eight steps, each yielding different molecules (italicized below).

With the help of catalyzing enzymes, one acetyl CoA (2-carbon) reacts with oxaloacetic acid (4-carbon), forming the 6-carbon molecule citrate.

Next, citrate is converted into one of its isomers, isocitrate, through a two-part process in which water is removed and added.

The third step yields α-ketoglutarate (5-carbon) from oxidized isocitrate. This process releases CO₂ and reduces NAD⁺ to NADH.

The fourth step forms the unstable compound succinyl CoA from α-ketoglutarate, a process that also releases CO₂ and reduces NAD⁺ to NADH.

The fifth step produces succinate (4-carbon) after a phosphate group replaces the CoA group of succinyl CoA. This phosphate group is passed on to ADP (or GDP) to form ATP (or GTP).

The sixth step forms fumarate (4-carbon) from the oxidation of succinate. This reaction reduces FAD to FADH₂.

The seventh step, in which water is added to fumarate, generates malate (4-carbon).

The final step produces oxaloacetate, the compound that reacts with acetyl CoA in step one, from the oxidation of malate. In the process, NAD⁺ is reduced to NADH.

The NADH and FADH₂ produced in the citric acid cycle provide electrons in the electron transport chain and, hence, aid the production of additional ATP.

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Citric Acid Cycle

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