Biochemistry: Citric Acid Cycle

Each of the steps of the CAC require a specific enzyme to facilitate the chemical reaction. The enzymes needed for the CAC are located in the matrix of the mitochondria, so that is where the CAC reaction occurs. A metabolic reaction always occurs where the enzymes needed for the reaction are located.

Acetyl CoA is the input required for the CAC to begin. The most important output of the CAC are the reduced coenzymes FADH2 and NADH. Each time the CAC is completed three NADH and one FADH2 are made.
Oxaloacetate is the product in the final step of the CAC (step 8). The creation of oxaloacetate in the last step, combined with its use as a reactant in step 1 of the next CAC, makes the CAC a cyclical process.

The Acetyl CoA input for the CAC can come from the breakdown of carbohydrate (glycolysis), lipid (beta oxidation) or protein (transamination).
After pyruvate has been produced in glycolysis (from glucose) it is converted to Acetyl CoA when oxygen is present. Oxygen is needed for a later step in the common metabolic pathway that is linked to the CAC.

The electron rich coenzymes produced in the CAC (1 FADH2 and 3 NADH) are taken to the electron transport chain, where they off-load their electrons to begin the electron transport chain (ETC).

The CAC produces the electron rich coenzymes (1 FADH2 and 3 NADH) which are needed to start the next step in the common metabolic pathway, the electron transport chain. The CAC is needed to continue the bioenergetic pathway, with the last step of the pathway creating a lot of ATP.

Enzymatic control of the CAC allows the CAC to be performed when ATP is required, whereas when there is already a lot of ATP the CAC will stop. The enzymes are needed to facilitate each of the CAC reactions.
Some of these enzymes are allosteric, which means they have regulatory binding sites. Positive and negative regulators bind to the enzyme’s regulatory binding site to increase and decrease the activity of the enzyme, respectively. For example, when an enzyme binds a negative regulator such as ATP, the enzyme can no longer facilitate the reaction which causes the chemical reaction to stop.

The acetyl CoA input is created from pyruvate (from glycolysis). Alternatively, acetyl CoA can also be generated from beta oxidation of fatty acids.
Oxaloacetate is made in the last step (step 8) of the citric acid cycle from malate. Oxaloacetate can also be made from pyruvate.

In steps 3, 4, 8 of the CAC, NAD+ is reduced to NADH, which allows the reactant to be oxidised where the reactant loses one or two hydrogen atoms.
In step 3, one of the alcohol groups of isocitrate is oxidised to a ketone group due to the loss of two hydrogen atoms (accepted by NAD+ to become NADH).
In step 4, the CoA loses a hydrogen atom (accepted by NAD+ to become NADH), which facilitates the attachment of the CoA to the alpha ketogluterate, which generates Succinyl CoA.
In step 8, one of the alcohol groups of malate is oxidised to a ketone group due to the loss of two hydrogen atom (accepted by NAD+ to become NADH), resulting in the compound becoming oxaloacetate.

In step 6 of the CAC, FAD is reduced to FADH2, which allows the reactant to be oxidised where the reactant loses two hydrogen atoms.
Once succinate loses two hydrogen atoms, the two central carbon atoms form an additional carbon-carbon bond, which results in the formation of a double carbon-carbon bond.
Once the double carbon-carbon bond has formed the compound is now fumarate.

The oxaloacetate created in the last step of the CAC is used to begin another cycle of the CAC. Oxaloacetate is one of the two inputs required for the first step of the CAC (Acetyl CoA and oxaloacetate are required).