AA - Arachidonic Acid | Elisa - Clia - Antibody - Protein

Background

Arachidonic Acid (AA) is a polyunsaturated omega-6 fatty acid that plays a pivotal role in cellular signaling, inflammation, and the synthesis of bioactive molecules. It is an essential fatty acid, meaning that while the body can synthesize it from linoleic acid (an omega-6 fatty acid), it cannot produce it from scratch and thus must obtain it from the diet or the conversion of other fatty acids. Arachidonic acid is found predominantly in the phospholipids of cell membranes, especially in the brain, liver, and muscle tissues. It is particularly abundant in the phosphatidylinositol and phosphatidylcholine components of the cell membrane.

Arachidonic acid plays a key role in cellular signaling, inflammation, and immune responses by being a precursor to a group of molecules known as eicosanoids, which include prostaglandins, thromboxanes, leukotrienes, and lipoxins. These bioactive lipid mediators are involved in a wide range of physiological processes, including inflammation, blood clotting, vascular tone regulation, and immune function. Arachidonic acid can be metabolized via several enzyme pathways, with the most prominent being those mediated by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 enzymes.

The balance of arachidonic acid metabolism is crucial in the body, as it can promote either pro-inflammatory or anti-inflammatory responses depending on the context and types of eicosanoids produced. Dysregulation of arachidonic acid metabolism has been implicated in various diseases, including cardiovascular disease, asthma, arthritis, and cancer.

Chemical Structure

Arachidonic acid is a 20-carbon fatty acid with four double bonds (C20:4, n-6), making it a polyunsaturated fatty acid. The structure of arachidonic acid consists of a long hydrocarbon chain with four cis-double bonds at positions 5, 8, 11, and 14. This structure is important for its function as a precursor to bioactive molecules, as the unsaturation in the fatty acid chain allows for its incorporation into the phospholipids of cell membranes, making it readily available for enzymatic conversion to eicosanoids.

• Molecular Formula: C20H32O2
• IUPAC Name: (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid
• Molecular Weight: 304.45 g/mol

The cis-double bonds create a kink in the molecular structure, contributing to the fatty acid's flexibility and allowing it to interact with enzymes and cell membrane proteins effectively.

Sources and Metabolism

Arachidonic acid can be obtained from the diet, particularly from animal fats, egg yolks, and fish oils, or it can be synthesized from linoleic acid, which is an essential fatty acid found in plant oils such as corn oil, sunflower oil, and soybean oil. Linoleic acid is converted to arachidonic acid via the action of enzymes, such as desaturases and elongases. The body can use arachidonic acid to generate eicosanoids or store it in the phospholipids of cellular membranes for later use.

In cells, arachidonic acid is predominantly stored in the phospholipids of the cell membrane, where it is esterified to the sn-2 position of phospholipids, particularly in the inner leaflet of the plasma membrane. Upon stimulation by external signals (e.g., hormones, cytokines, or growth factors), arachidonic acid is released from the membrane through the action of phospholipase A2 (PLA2). Once freed, arachidonic acid can be metabolized through several key enzymatic pathways:

1. Cyclooxygenase (COX) Pathway:

• The COX-1 and COX-2 enzymes metabolize arachidonic acid into prostaglandins (PGs) and thromboxanes (TXs), which are involved in regulating inflammation, fever, and blood clotting. COX-1 is constitutively expressed in most tissues, while COX-2 is induced during inflammation.

1. Lipoxygenase (LOX) Pathway:

• Arachidonic acid can also be metabolized by lipoxygenases to produce leukotrienes (LTs) and lipoxins. Leukotrienes play key roles in allergic reactions, bronchoconstriction, and immune responses, whereas lipoxins are involved in resolving inflammation.

1. Cytochrome P450 (CYP450) Pathway:

• The cytochrome P450 enzymes also metabolize arachidonic acid, generating a variety of epoxyeicosatrienoic acids (EETs), which have important functions in vascular tone regulation and renal function.

Biological Significance

Arachidonic acid is involved in numerous biological processes, particularly in inflammation, immune response, cell signaling, and vascular regulation:

1. Involvement in Inflammation: Arachidonic acid is the precursor for a wide variety of pro-inflammatory mediators (prostaglandins and leukotrienes) that are involved in the body’s immune response to injury or infection. Inflammatory stimuli activate phospholipase A2, which releases arachidonic acid from phospholipids. Arachidonic acid is then converted by COX and LOX enzymes into inflammatory mediators, which promote vasodilation, increased vascular permeability, and the recruitment of immune cells to sites of inflammation.
2. Blood Clotting: Through the COX-1 pathway, arachidonic acid is converted into thromboxane A2 (TXA2), a potent vasoconstrictor and platelet aggregator. TXA2 plays a crucial role in blood clot formation by facilitating platelet aggregation and vasoconstriction, which are key steps in the hemostatic response to vascular injury.
3. Vascular Tone Regulation: Arachidonic acid metabolites, including epoxyeicosatrienoic acids (EETs), help regulate vascular tone by inducing vasodilation and influencing renal function. EETs play a significant role in the maintenance of blood pressure and the response to changes in vascular resistance.
4. Neurotransmission and Brain Function: Arachidonic acid and its metabolites influence neurotransmission and brain function. In the central nervous system, arachidonic acid metabolites are involved in synaptic plasticity, neuroinflammation, and neurotransmitter release, which impact learning, memory, and mood regulation. Alterations in arachidonic acid metabolism have been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia.
5. Cell Growth and Differentiation: Arachidonic acid metabolites, particularly prostaglandins, are involved in regulating cell growth and differentiation. These metabolites influence processes such as cell proliferation, apoptosis, and the immune response, all of which are important for tissue repair, development, and the prevention of tumorigenesis.

Clinical Issues

Given its central role in inflammation, cell signaling, and immune responses, dysregulation of arachidonic acid metabolism has been implicated in a wide range of diseases:

1. Inflammatory Disorders: Overproduction of pro-inflammatory eicosanoids derived from arachidonic acid has been linked to a variety of inflammatory diseases, such as rheumatoid arthritis, asthma, inflammatory bowel disease, and psoriasis. In these conditions, the immune system overreacts, producing excessive inflammation that damages tissues and impairs normal function.
2. Cardiovascular Disease: Arachidonic acid-derived thromboxane A2 (TXA2) plays a role in platelet aggregation and vasoconstriction. Dysregulation of this pathway can lead to increased blood clotting, contributing to atherosclerosis, heart attack, and stroke. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX enzymes, are often used to reduce inflammation and manage pain, but they can also decrease the risk of clotting-related cardiovascular events.
3. Cancer: Altered metabolism of arachidonic acid, particularly through the COX-2 pathway, has been implicated in cancer. Overexpression of COX-2 in tumors promotes the production of prostaglandins, which enhance tumor growth, angiogenesis, and metastasis. COX-2 inhibitors have been studied as potential cancer therapies.
4. Neurodegenerative Diseases: Disruptions in arachidonic acid metabolism in the brain have been linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, where inflammatory processes mediated by arachidonic acid metabolites contribute to neuronal damage and cognitive decline.
5. Asthma and Allergies: Arachidonic acid-derived leukotrienes play a critical role in bronchoconstriction and inflammation in asthma. Leukotriene receptor antagonists are used to treat asthma and allergic rhinitis by blocking the effects of leukotrienes, thereby reducing airway inflammation and constriction.

Summary

Arachidonic acid (AA) is a polyunsaturated fatty acid that serves as a precursor for a variety of bioactive molecules, including prostaglandins, thromboxanes, leukotrienes, and lipoxins, which are involved in regulating inflammation, immune responses, blood clotting, and vascular tone. AA plays a central role in cell signaling, neuronal function, tissue repair, and metabolic regulation. Dysregulation of arachidonic acid metabolism is linked to numerous diseases, including inflammatory disorders, cardiovascular diseases, cancer, and neurodegenerative conditions. Understanding the metabolism of arachidonic acid and its derivatives is crucial for developing targeted therapies for these diseases.