The Epoxyeicosatrienoic acids or EETs are signaling molecules formed by the action of Cytochrome P450 epoxygenase

Cytochrome P450 oxidase

The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...

 on 20-carbon essential fatty acid

Essential fatty acid

Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them...

s, such as arachidonic acid

Arachidonic acid

Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

, from which it is produced by the enzyme epoxygenase

Epoxygenase

Epoxygenase is an enzyme that produces hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids from arachidonic acid, causing effects such as cell proliferation and decrease in cyclooxygenase activity. -HETEs:...

.

These nonclassic eicosanoid

Nonclassic eicosanoid

Nonclassic eicosanoids are biologically active signaling molecules made by oxygenation of twenty-carbon fatty acids other than the classic eicosanoids.-Terminology:"Eicosanoid" is the collective...

s act as short-range hormone

Hormone

A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s, (i.e. they are autocrine

Autocrine signalling

Autocrine signaling is a form of signalling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on the same cell, leading to changes in the cell...

 and paracrine

Paracrine signalling

Paracrine signalling is a form of cell signalling in which the target cell is near the signal-releasing cell.-Local action:Some signalling molecules degrade very quickly, limiting the scope of their effectiveness to the immediate surroundings...

 mediators) of the cardiovascular system and kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

. They produce vasorelaxation as well as anti-inflammatory

Anti-inflammatory

Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

 and pro-fibrinolytic

Fibrinolysis

Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...

 effects.
EETs are metabolized by the soluble epoxide hydrolase

Soluble epoxide hydrolase

In enzymology, a soluble epoxide hydrolase or sEH is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are epoxide and H2O, whereas its product is glycol....

 to the corresponding vicinal diol

Diol

A diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...

, or dihydroxyeicosatrienoic acids (DHETs), which are biologically less active.

Biological effects

Generally, EETs cause:

• Calcium
  Calcium
  Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
  
   release from intracellular stores
• Increased sodium-hydrogen antiporter
  Sodium-hydrogen antiporter
  The sodium–hydrogen antiporter or sodium–hydrogen exchanger is a membrane protein found in many cells, and especially in those of the nephron of the kidney...
  
   activity
• Increased cell proliferation
• Decreased cyclooxygenase
  Cyclooxygenase
  Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
  
   activity

Other effects are specific to certain cells or locations:

• EETs are cardioprotective after ischemic heart attack
  Myocardial infarction
  Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
  
   and reperfusion.
• They act in the corpus cavernosum
  Corpus cavernosum penis
  The corpus cavernosum penis is one of a pair of sponge-like regions of erectile tissue which contain most of the blood in the penis during penile erection...
  
    to maintain penile erection.
• Specific epoxidation of EET sites produces endogenous PPARα agonists.
• Decreased release of somatostatin
  Somatostatin
  Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
  
  , insulin
  Insulin
  Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
  
   and glucagon
  Glucagon
  Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
  
   from endocrine cells.
• Vasodilation
  Vasodilation
  Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
  
   and angiogenesis
  Angiogenesis
  Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
  
   in blood vessels.
• Increased risk of tumor adhesion on endothelial cells
• Decreased platelet aggregation