ACETYL COENZYME A: STRUCTURE, FORMATION AND FUNCTIONS - BIOLOGY - 2024

The acetyl coenzyme A, acetyl CoA abbreviated, is an intermediate molecule crucial to various metabolic pathways of both lipid and protein and carbohydrates. Its main functions include delivering the acetyl group to the Krebs cycle.

The origin of the acetyl coenzyme A molecule can occur through different routes; This molecule can form inside or outside the mitochondria, depending on how much glucose is in the environment. Another characteristic of acetyl CoA is that energy is produced with its oxidation.

Structure

Coenzyme A is made up of a β-mercaptoethylamine group linked by a bond to vitamin B5, also called pantothenic acid. Likewise, this molecule is linked to a 3'-phosphorylated nucleotide ADP. An acetyl group (-COCH ₃) is attached to this structure.

The chemical formula of this molecule is C ₂₃ H ₃₈ N ₇ O ₁₇ P ₃ S and it has a molecular weight of 809.5 g / mol.

Training

As mentioned above, the formation of acetyl CoA can take place inside or outside the mitochondria, and depends on the levels of glucose present in the medium.

Intramitochondrial

When glucose levels are high, acetyl CoA is formed as follows: the end product of glycolysis is pyruvate. For this compound to enter the Krebs cycle, it must be transformed into acetyl CoA.

This step is crucial to connect glycolysis with the other processes of cellular respiration. This step occurs in the mitochondrial matrix (in prokaryotes it occurs in the cytosol). The reaction involves the following steps:

- For this reaction to take place, the pyruvate molecule must enter the mitochondria.

- The carboxyl group of pyruvate is removed.

- Subsequently, this molecule is oxidized. The latter for involves the passage from NAD + to NADH thanks to the electrons product of the oxidation.

- The oxidized molecule binds to coenzyme A.

The reactions necessary for the production of acetyl coenzyme A are catalyzed by an enzyme complex of significant size called pyruvate dehydrogenase. This reaction requires the presence of a group of cofactors.

This step is critical in the process of cell regulation, since the amount of acetyl CoA that enters the Krebs cycle is decided here.

When levels are low, the production of acetyl coenzyme A is carried out by the β-oxidation of fatty acids.

Extramitochondrial

When glucose levels are high, the amount of citrate also increases. Citrate is transformed into acetyl coezyme A and oxaloacetate by the enzyme ATP citrate lyase.

In contrast, when levels are low, CoA is acetylated by acetyl CoA synthetase. In the same way, ethanol serves as a source of carbons for acetylation by means of the enzyme alcohol dehydrogenase.

Features

Acetyl-CoA is present in a number of varied metabolic pathways. Some of these are as follows:

Citric acid cycle

Acetyl CoA is the fuel needed to start this cycle. Acetyl coenzyme A is condensed together with a molecule of oxaloacetic acid into citrate, a reaction catalyzed by the enzyme citrate synthase.

The atoms of this molecule continue their oxidation until they form CO ₂. For every molecule of acetyl CoA that enters the cycle, 12 molecules of ATP are generated.

Lipid metabolism

Acetyl CoA is an important product of lipid metabolism. For a lipid to become an acetyl coenzyme A molecule, the following enzymatic steps are required:

- Fatty acids must be “activated”. This process consists of the fatty acid binding to CoA. To do this, an ATP molecule is cleaved to provide the energy that allows this union.

- Oxidation of acyl coenzyme A occurs, specifically between the α and β carbons. Now, the molecule is called acyl-a enoyl CoA. This step involves the conversion of FAD to FADH ₂ (takes the hydrogens).

- The double bond formed in the previous step receives an H on the alpha carbon and a hydroxyl (-OH) on the beta.

- β-oxidation occurs (β because the process occurs at the level of that carbon). The hydroxyl group transforms into a keto group.

- A molecule of coenzyme A cleaves the bond between the carbons. Said compound is bound to the remaining fatty acid. The product is one molecule of acetyl CoA and another with two fewer carbon atoms (the length of the last compound depends on the initial length of the lipid. For example, if it had 18 carbons, the result would be 16 final carbons).

This four-step metabolic route: oxidation, hydration, oxidation and thiolysis, which is repeated until two molecules of acetyl CoA remain as the final product. That is, all grade acid becomes acetyl CoA.

It is worth remembering that this molecule is the main fuel of the Krebs cycle and can enter it. Energetically, this process produces more ATP than carbohydrate metabolism.

Synthesis of ketone bodies

The formation of ketone bodies occurs from a molecule of acetyl coenzyme A, a product of lipid oxidation. This pathway is called ketogenesis and it occurs in the liver; specifically, it occurs in the mitochondria of liver cells.

Ketone bodies are a heterogeneous set of compounds soluble in water. They are the water-soluble version of fatty acids.

Its fundamental role is to act as fuels for certain tissues. Particularly in fasting stages, the brain can take in ketone bodies as an energy source. Under normal conditions, the brain uses glucose.

Glyoxylate cycle

This pathway occurs in a specialized organelle called the glyoxysome, present only in plants and other organisms, such as protozoa. Acetyl coenzyme A is converted to succinate and can be re-incorporated into the Krebs acid cycle.

In other words, this pathway makes it possible to skip certain reactions of the Krebs cycle. This molecule can be converted to malate, which in turn can be converted to glucose.

Animals do not have the metabolism necessary to carry out this reaction; therefore, they are unable to carry out this synthesis of sugars. In animals all the acetyl CoA carbons are oxidized to CO ₂, which is not useful for a biosynthetic pathway.

The end product of fatty acid degradation is acetyl coenzyme A. Therefore, in animals this compound cannot be reintroduced for synthesis.

References

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3. Koolman, J., & Röhm, KH (2005). Biochemistry: text and atlas. Panamerican Medical Ed.
4. Peña, A., Arroyo, A., Gómez, A., & Tapia R. (2004). Biochemistry. Editorial Limusa.
5. Voet, D., & Voet, JG (2006). Biochemistry. Panamerican Medical Ed.