Thromboxane is a member of the family of lipids Lipids are a broad group of naturally occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others. The main biological functions of lipids include energy storage, as structural components of cell membranes, and as important signaling molecules known as eicosanoids In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, . They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. The networks of controls that depend upon eicosanoids are among the most complex in the human body. The two major thromboxanes are thromboxane A2 Thromboxane A2 is a thromboxane. It is generated from prostaglandin H2 by thromboxane-A synthase. It is also a major component of blood clots. Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2 and thromboxane B2.

Thromboxane is named for its role in clot formation (thrombosis Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss. If the clotting is too severe and the clot breaks free, the traveling clot is now know as an).

Contents

Production

Enzymes and substrates associated with thromoboxane and prostacyclin synthesis. Eicosanoid synthesis.

Thromboxane-A synthase This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence, an enzyme found in platelets Platelets, or thrombocytes , are small, irregularly-shaped anuclear cell fragments (i.e. cells that do not have a nucleus containing DNA), 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days. Platelets play a fundamental role in hemostasis and are a, converts the arachidonic acid Arachidonic acid is an omega-6 fatty acid 20:4(ω-6). It is the counterpart to the saturated arachidic acid found in peanut oil, (L. arachis – peanut.) derivative prostaglandin H2 Prostaglandin H2 is a type of Prostaglandin which is derived from arachidonic acid and is a precursor for many other biologically significant molecules: to thromboxane.

Mechanism

Thromboxane acts by binding to any of the thromboxane receptors, G-protein coupled receptors G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, coupled to the G protein G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors Gq Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes phosphatidylinositol (PIP2) to diacyl glycerol (DAG) and inositol triphosphate (IP3) signal transduction pathway. DAG acts as a second messenger that activates Protein Kinase C (PKC) and IP3 helps in phosphorylation of some proteins[1].

Functions

Thromboxane is a vasoconstrictor Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in staunching hemorrhage and acute blood loss. When and a potent hypertensive agent, and it facilitates platelet aggregation.

It is in homeostatic Homeostasis is the property of a system, either open or closed, that regulates its internal environment and tends to maintain a stable, constant condition. Typically used to refer to a living organism, the concept came from that of milieu interieur that was created by Claude Bernard and published in 1865. Multiple dynamic equilibrium adjustment balance in the circulatory system The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis with prostacyclin Prostacyclin is a member of the family of lipid molecules known as eicosanoids, a related compound. The mechanism of secretion of thromboxanes from platelets is still unclear.

Role of A2 in platelet aggregation

Thromboxane A2 (TXA2), produced by activated platelets, has prothrombotic properties, stimulating activation of new platelets as well as increasing platelet aggregation.

Platelet aggregation is achieved by mediating expression of the glycoprotein complex GP IIb/IIIa In medicine, glycoprotein IIb/IIIa, also gpIIb/IIIa, is an integrin found on platelets. It is a receptor for fibrinogen and aids in platelet activation. The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence. Platelet activation by ADP leads to a in the cell membrane of platelets. Circulating fibrinogen Fibrin is a fibrous protein involved in the clotting of blood, and is non globular. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot (in conjunction with platelets) over a wound site binds these receptors on adjacent platelets, further strengthening the clot A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors). A thrombus is normal in cases of injury, but pathologic in instances of thrombosis.

Pathology

It is believed that the vasoconstriction caused by thromboxanes plays a role in Prinzmetal's angina.

Suppression

See also: Mechanism of action of aspirin and Aspirin Aspirin , also known as acetylsalicylic acid (pronounced /əˌsɛtəlˌsælɨˈsɪlɨk/ ə-SET-əl-sal-i-SIL-ik, abbreviated ASA), is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication

The widely used drug aspirin Aspirin , also known as acetylsalicylic acid (pronounced /əˌsɛtəlˌsælɨˈsɪlɨk/ ə-SET-əl-sal-i-SIL-ik, abbreviated ASA), is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication acts by inhibiting the ability of the COX enzyme to synthesize the precursors of thromboxane within platelets. Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 Thromboxane A2 is a thromboxane. It is generated from prostaglandin H2 by thromboxane-A synthase. It is also a major component of blood clots. Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2 in platelets Platelets, or thrombocytes , are small, irregularly-shaped anuclear cell fragments (i.e. cells that do not have a nucleus containing DNA), 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days. Platelets play a fundamental role in hemostasis and are a, producing an inhibitory effect on platelet aggregation Platelets, or thrombocytes , are small, irregularly-shaped anuclear cell fragments (i.e. cells that do not have a nucleus containing DNA), 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days. Platelets play a fundamental role in hemostasis and are a. This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks.[2] 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.[3]

See also

Nota Bene

Thromboxane synthetase is misnamed for thromboxane synthase but is often found in the literature.

References

  1. ^ Rat kidney thromboxane receptor: molecular cloning, signal ...
  2. ^ [1] American Heart Association: Aspirin in Heart Attack and Stroke Prevention "The American Heart Association recommends aspirin use for patients who've had a myocardial infarction (heart attack), unstable angina, ischemic stroke (caused by blood clot) or transient ischemic attacks (TIAs or "little strokes"), if not contraindicated. This recommendation is based on sound evidence from clinical trials showing that aspirin helps prevent the recurrence of such events as heart attack, hospitalization for recurrent angina, second strokes, etc. (secondary prevention). Studies show aspirin also helps prevent these events from occurring in people at high risk (primary prevention)."
  3. ^ Tohgi, H; S Konno, K Tamura, B Kimura and K Kawano (1992). "Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin". Stroke Vol 23 (10): 1400–1403. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 1412574.

External links

Autacoids Autacoids are biological factors which act like local hormones, have a brief duration, act near the site of synthesis, and are not blood borne. Autacoids are primarily characterized by the effect they have upon smooth muscle. With respect to vascular smooth muscle, there are both vasoconstrictor and vasodilator autacoids, unsaturated An unsaturated fat is a fat or fatty acid in which there is at least one double bond within the fatty acid chain. A fat molecule is monounsaturated if it contains one double bond, and polyunsaturated if it contains more than one double bond. Where double bonds are formed, hydrogen atoms are eliminated. Thus, a saturated fat has no double bonds, fatty acids In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. The most occurring natural fatty acids have an even number of carbon atoms because their biosynthesis involves acetyl-CoA, a coenzyme carrying a two-carbon-atom group (see fatty acid synthesis): Eicosanoids In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, . They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. The networks of controls that depend upon eicosanoids are among the most complex in the human body
Precursor Arachidonic acid Arachidonic acid is an omega-6 fatty acid 20:4(ω-6). It is the counterpart to the saturated arachidic acid found in peanut oil, (L. arachis – peanut.)
Prostanoids Cyclooxygenase catalyzes the conversion of the free essential fatty acids to prostanoids by a two-step process. In the first step, two molecules of O2 are added as two peroxide linkages and a 5-member carbon ring is forged near the middle of the fatty acid chain. This forms the short-lived, unstable intermediate Prostaglandin G (PGG). One of the
Prostaglandins A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring (PG) and analogues coumarins: Acenocoumarol • Coumatetralyl • Dicoumarol • Ethyl biscoumacetate • Phenprocoumon • Warfarin
Precursor H2 Prostaglandin H2 is a type of Prostaglandin which is derived from arachidonic acid and is a precursor for many other biologically significant molecules:
Active
D/J D2 Prostaglandin D2 is a prostaglandin which binds to the receptor PTGDR, as well as CRTH2. It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, basophils. In mammalian organs, large amounts of PGD2 are found in the brain, in mast cells and found nowhere else. It is critical to development of allergic diseases such
E/F

E2 (Dinoprostone): Enprostil · Sulprostone

E1 (Alprostadil): Misoprostol Misoprostol is a drug that is used for the prevention of non-steroidal anti-inflammatory drug -induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The last use is controversial in the United States. Misoprostol was invented and marketed by G.D. Searle & Company (now Pfizer) under the trade name Cytotec · Gemeprost Gemeprost is an analogue of prostaglandin E1

F2α (Dinoprost): Bimatoprost Bimatoprost is a prostaglandin analog used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. It reduces intraocular pressure (IOP) by increasing the outflow of aqueous fluid from the eyes. It has also been used and prescribed off-label to lengthen eyelashes. In December 2008, this use was · Carboprost · Latanoprost · Tafluprost · Travoprost · Unoprostone
I I2 (Prostacyclin/Epoprostenol) Prostacyclin is a member of the family of lipid molecules known as eicosanoids: Beraprost · Iloprost · Treprostinil
Thromboxanes (TX) A2 Thromboxane A2 is a thromboxane. It is generated from prostaglandin H2 by thromboxane-A synthase. It is also a major component of blood clots. Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2 · B2
Leukotrienes Leukotrienes are fatty molecules of the immune system that contribute to inflammation in asthma and allergic rhinitis. Leukotriene antagonists are used to treat these diseases (LT)
Precursor Arachidonic acid 5-hydroperoxide
Initial A4 · B4
SRS-A C4 · D4 · E4
Nonclassic Lipoxins Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation. They are abbreviated as LX, an acronym for lipoxygenase interaction products. At present two lipoxins have been identified; lipoxin A4 (LXA4) and (A4, B4) · Virodhamine Virodhamine is an endocannabinoid and a nonclassic eicosanoid, derived from arachidonic acid. O-Arachidonoyl ethanolamine is arachidonic acid and ethanolamine joined by an ester linkage, the opposite of the amide linkage found in anandamide. Based on this opposite orientation, the molecule was named virodhamine from the Sanskrit word virodha,
By function

bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding fibdh, with consequent coughing, wheezing, and shortness of breath. Bronchoconstriction can also be due to an accumulation of thick mucus (PGF2α, TXA2 Thromboxane A2 is a thromboxane. It is generated from prostaglandin H2 by thromboxane-A synthase. It is also a major component of blood clots. Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2, LTC4, LTD4, LTE4)

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in staunching hemorrhage and acute blood loss. When (PGF2α, TXA2 Thromboxane A2 is a thromboxane. It is generated from prostaglandin H2 by thromboxane-A synthase. It is also a major component of blood clots. Aspirin irreversibly inhibits platelet cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2, TXB2) · 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 vessels dilate, the flow of blood is increased (PGE2, PGI2 Prostacyclin is a member of the family of lipid molecules known as eicosanoids, LTC4, LTD4, LTE4)

platelets Platelets, or thrombocytes , are small, irregularly-shaped anuclear cell fragments (i.e. cells that do not have a nucleus containing DNA), 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days. Platelets play a fundamental role in hemostasis and are a: induce (TXA2) inhibit (PGD2, PGI2) · leukocytes: induce (TXA2, LTB4) inhibit (PGD2, PGE2)

labor stimulation: (PGE2 (Dinoprostone), PGF2α (Dinoprost))
see also

Categories: Eicosanoids

 

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