Arachidonic acid in the context of "Prostaglandin"

Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of their cells of origin. Some eicosanoids, such as prostaglandins, may also have endocrine roles as hormones to influence the function of distant cells.

There are multiple subfamilies of eicosanoids, including most prominently the prostaglandins, thromboxanes, leukotrienes, lipoxins, resolvins, and eoxins. For each subfamily, there is the potential to have at least 4 separate series of metabolites, two series derived from the ω−6 PUFAs arachidonic and dihomo-gamma-linolenic acids, one series derived from the ω−3 PUFA eicosapentaenoic acid, and one series derived from the ω−9 PUFA mead acid. This subfamily distinction is important. Mammals, including humans, are unable to convert ω−6 into ω−3 PUFA. In consequence, tissue levels of the ω−6 and ω−3 PUFAs and their corresponding eicosanoid metabolites link directly to the amount of dietary ω−6 versus ω−3 PUFAs consumed. Since certain of the ω−6 and ω−3 PUFA series of metabolites have almost diametrically opposing physiological and pathological activities, it has often been suggested that the deleterious consequences associated with the consumption of ω−6 PUFA-rich diets reflects excessive production and activities of ω−6 PUFA-derived eicosanoids, while the beneficial effects associated with the consumption of ω−3 PUFA-rich diets reflect the excessive production and activities of ω−3 PUFA-derived eicosanoids. In this view, the opposing effects of ω−6 PUFA-derived and ω−3 PUFA-derived eicosanoids on key target cells underlie the detrimental and beneficial effects of ω−6 and ω−3 PUFA-rich diets on inflammation and allergy reactions, atherosclerosis, hypertension, cancer growth, and a host of other processes.

Platelet-activating factor, also known as PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine), is a potent phospholipid activator and mediator of many leukocyte functions, platelet aggregation and degranulation, inflammation, and anaphylaxis. It is also involved in changes to vascular permeability, the oxidative burst, chemotaxis of leukocytes, as well as augmentation of arachidonic acid metabolism in phagocytes.

PAF is produced by a variety of cells, but especially those involved in host defense, such as platelets, endothelial cells, neutrophils, monocytes, and macrophages. PAF is continuously produced by these cells but in low quantities and production is controlled by the activity of PAF acetylhydrolases. It is produced in larger quantities by inflammatory cells in response to specific stimuli.

The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the central nervous system (including the brain) and peripheral nervous system. It is found in animals as simple as hydras, but absent in insects, who are hypothesized to have lost it due to a lack of arachidonic acid. The endocannabinoid system is still not fully understood, but may be involved in regulating physiological and cognitive processes, including fertility, pregnancy, pre- and postnatal development, various activity of immune system, appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis. The ECS plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.

Two primary cannabinoid receptors have been identified: CB₁, first cloned (or isolated) in 1990; and CB₂, cloned in 1993. CB₁ receptors are found predominantly in the brain and nervous system, as well as in peripheral organs and tissues, and are the main molecular target of the fatty-acid neurotransmitter anandamide, as well as the most known active component of cannabis, tetrahydrocannabinol (THC). Another endocannabinoid, 2-arachidonoylglycerol (2-AG), also interacts with both CB receptors. It is significantly more abundant in the mammalian brain than anandamide, exceeding it by two to three orders of magnitude.

γ-Linolenic acid or GLA (INN: gamolenic acid) is an n−6, or omega-6, fatty acid found primarily in seed oils. When acting on GLA, arachidonate 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid to leukotrienes is inhibited.

A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze:

• Phospholipase A
  • Phospholipase A₁ – cleaves the sn-1 acyl chain (where sn refers to stereospecific numbering).
  • Phospholipase A₂ – cleaves the sn-2 acyl chain, releasing arachidonic acid.
• Phospholipase B – cleaves both sn-1 and sn-2 acyl chains; this enzyme is also known as a lysophospholipase.
• Phospholipase C – cleaves before the phosphate, releasing diacylglycerol and a phosphate-containing head group. PLCs play a central role in signal transduction, releasing the second messenger inositol triphosphate.
• Phospholipase D – cleaves after the phosphate, releasing phosphatidic acid and an alcohol.

Types C and D are considered phosphodiesterases.