ARACHIDONIC ACID: FUNCTIONS, DIET, CASCADE - BIOLOGY - 2024

The arachidonic acid is a compound of 20 carbons. It is a polyunsaturated fatty acid, because it has double bonds between its carbons. These double bonds are in position 5, 8, 11 and 14. Due to the position of their bonds, they belong to the group of omega-6 fatty acids.

All eicosanoids - lipid molecules involved in various pathways with vital biological functions (eg, inflammation) - come from this 20-carbon fatty acid. Much of the arachidonic acid is found in the phospholipids of the cell membrane and can be released by a number of enzymes.

Arachidonic acid is involved in two pathways: the cyclooxygenase pathway and the lipoxygenase pathway. The former gives rise to the formation of prostaglandins, thromboxanes and prostacyclin, while the latter generates leukotrienes. These two enzymatic pathways are unrelated.

Features

Arachidonic acid has a wide range of biological functions, among these are:

- It is an integral constituent of the cell membrane, giving it the fluidity and flexibility necessary for the normal function of the cell. This acid also undergoes deacylation / reacylation cycles when found as a phospholipid in membranes. The process is also known as the Lands cycle.

- It is found particularly in the cells of the nervous, skeletal and immune systems.

- In skeletal muscle it helps its repair and growth. The process occurs after physical activity.

- Not only the metabolites produced by this compound have biological importance. Acid in its free state is capable of modulating different ion channels, receptors and enzymes, either activating or deactivating them through different mechanisms.

- The metabolites derived from this acid contribute to inflammatory processes and lead to the generation of mediators that are responsible for solving these problems.

- Free acid, together with its metabolites, promotes and modulates immune responses responsible for resistance to parasites and allergies.

Arachidonic acid in the diet

Arachidonic acid generally comes from the diet. It is abundant in products of animal origin, in different types of meat, eggs, among other foods.

However, its synthesis is possible. To perform it, linoleic acid is used as a precursor. This is a fatty acid that has 18 carbon atoms in its structure. It is an essential fatty acid in the diet.

Arachidonic acid is not essential if enough linoleic acid is available. The latter is found in significant quantities in foods of plant origin.

Arachidonic Acid Cascade

Different stimuli can promote the release of arachidonic acid. They can be of the hormonal, mechanical or chemical type.

Arachidonic acid release

Once the necessary signal is given, the acid is released from the cell membrane by means of the enzyme phospholipase A ₂ (PLA2), but platelets, in addition to having PLA2, also possess a phospholipase C.

Acid alone can act as a second messenger, modifying other biological processes in turn, or it can be converted into different eicosanoid molecules following two different enzymatic pathways.

It can be released by different cyclooxygenases and thromboxanes or prostaglandins are obtained. Likewise, it can be directed to the lipoxygenase pathway and leukotrienes, lipoxins and hepoxilins are obtained as derivatives.

Prostaglandins and thromboxanes

Arachidonic acid oxidation can take the pathway of cyclooxygenation and PGH synthetase, the products of which are prostaglandins (PG) and thromboxane.

There are two cyclooxygenases, in two separate genes. Each performs specific functions. The first, COX-1, is encoded on chromosome 9, is found in most tissues, and is constitutive; that is, it is always present.

In contrast, COX-2, encoded on chromosome 1, appears by hormonal action or other factors. Furthermore, COX-2 is related to inflammation processes.

The first products to be generated by COX catalysis are cyclic endoperoxides. Subsequently, the enzyme produces oxygenation and cyclization of the acid, forming PGG2.

Sequentially, the same enzyme (but this time with its peroxidase function) adds a hydroxyl group and converts PGG2 to PGH2. Other enzymes are responsible for the catalysis of PGH2 to prostanoids.

Functions of prostaglandins and thromboxanes

These lipid molecules act on different organs, such as muscle, platelets, kidneys and even bones. They also participate in a series of biological events such as the production of fever, inflammation and pain. They also have a role in the dream.

Specifically, COX-1 catalyzes the formation of compounds that are related to homeostasis, gastric cytoprotection, regulation of vascular and branchial tone, uterine contractions, kidney functions, and platelet aggregation.

That is why most drugs against inflammation and pain work by blocking cyclooxygenase enzymes. Some common drugs with this mechanism of action are aspirin, indomethacin, diclofenac, and ibuprofen.

Leukotrienes

These three-double bond molecules are produced by the enzyme lipoxygenase and are secreted by leukocytes. Leukotrienes can stay in the body for about four hours.

Lipoxygenase (LOX) incorporates an oxygen molecule into arachidonic acid. There are several LOXs described for humans; within this group the most important is 5-LOX.

5-LOX requires the presence of an activating protein (FLAP) for its activity. FLAP mediates the interaction between the enzyme and the substrate, allowing the reaction.

Functions of leukotrienes

Clinically they have an important role in processes related to the immune system. High levels of these compounds are associated with asthma, rhinitis and other hypersensitivity disorders.

Non-enzymatic metabolism

In the same way, metabolism can be carried out following non-enzymatic routes. That is, the enzymes mentioned previously do not work. When peroxidation occurs - a consequence of free radicals - isoprostanes originate.

Free radicals are molecules with unpaired electrons; therefore, they are unstable and need to react with other molecules. These compounds have been linked to aging and disease.

Isoprotanes are compounds quite similar to prostaglandins. By the way they are produced, they are markers of oxidative stress.

High levels of these compounds in the body are indicators of disease. They are abundant in smokers. Also, these molecules are related to inflammation and pain perception.

References

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5. Lands, WE (Ed.). (2012). Biochemistry of arachidonic acid metabolism. Springer Science & Business Media.
6. Tallima, H., & El Ridi, R. (2017). Arachidonic Acid: Physiological Roles and Potential Health Benefits. A Review. Journal of Advanced Research.