Prostacyclin (also called prostaglandin I 2 or PGI 2 ) is a prostaglandin member of the eicosanoid family of lipid molecules . It inhibits platelet activation and is also an effective vasodilator.
100-558: When used as a drug, it is also known as epoprostenol . The terms are sometimes used interchangeably. Prostacyclin chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator . Prostacyclin's interactions contrast with those of thromboxane (TXA 2 ), another eicosanoid. Both molecules are derived from arachidonic acid , and work together with opposite platelet aggregatory effects. These strongly suggest
200-470: A blocked coronary artery. As such, the same factors that cause platelets to coagulate during hemostasis can also contribute to unwanted thrombosis. While the general mechanisms of hemostasis and platelet plug formation have already been discovered, there is still much to learn in terms of the chemicals contributing to the process. Only the key factors have been identified; there are still many molecules present during hemostasis that scientists do not understand
300-445: A buffer to recruit or titrate ions or antibiotics. Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; it may contribute to biofilm formation; and it may contribute to the biofilm's physical strength and resistance to biological stress. Cell-free fetal DNA
400-459: A cell makes up its genome ; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes . Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into
500-450: A chain by covalent bonds (known as the phosphodiester linkage ) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone . The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups,
600-445: A complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation , which depends on the same interaction between RNA nucleotides. In an alternative fashion, a cell may copy its genetic information in a process called DNA replication . The details of these functions are covered in other articles; here
700-455: A controversial point, some assign COX 1 as the major prostacyclin producing cyclooxygenase in the endothelial cells of the blood vessels. The series-3 prostaglandin PGH 3 also follows the prostacyclin synthase pathway, yielding another prostacyclin, PGI 3 . The unqualified term 'prostacyclin' usually refers to PGI 2 . PGI 2 is derived from the ω-6 arachidonic acid . PGI 3 is derived from
800-492: A double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature . As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms. Most DNA molecules are actually two polymer strands, bound together in
900-428: A full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules. Each human cell contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500. However, the amount of mitochondria per cell also varies by cell type, and an egg cell can contain 100,000 mitochondria, corresponding to up to 1,500,000 copies of
1000-439: A helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperatures, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH
1100-571: A higher number is also possible but this would be against the natural principle of least effort . The phosphate groups of DNA give it similar acidic properties to phosphoric acid and it can be considered as a strong acid . It will be fully ionized at a normal cellular pH, releasing protons which leave behind negative charges on the phosphate groups. These negative charges protect DNA from breakdown by hydrolysis by repelling nucleophiles which could hydrolyze it. Pure DNA extracted from cells forms white, stringy clumps. The expression of genes
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#17328590978581200-400: A lipid mediator they called "PG-X," which inhibits platelet aggregation. PG-X, later known as prostacyclin, is 30 times more potent than any other then-known anti-aggregatory agent. They did this while searching for an enzyme that generates a fellow unstable prostanoid, Thromboxane A2 In 1976, Vane and fellow researchers Salvador Moncada , Ryszard Gryglewski , and Stuart Bunting published
1300-667: A long-standing puzzle known as the " C-value enigma ". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression . Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes , which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils , although they can occasionally serve as raw genetic material for
1400-500: A mechanism of cardiovascular homeostasis between these two hormones in relation to vascular damage. It is used to treat pulmonary arterial hypertension (PAH), pulmonary fibrosis , as well as atherosclerosis . Prostacyclins are given to people with class III or class IV PAH. Prostacyclin, which has a half-life of 42 seconds, is broken down into 6-keto-PGF 1 , which is a much weaker vasodilator. A way to stabilize prostacyclin in its active form, especially during drug delivery,
1500-409: A narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form . Here, the strands turn about
1600-418: A platelet plug, which prevents more blood from leaving the body as well as any outside contaminants from getting in. The plug provides a temporary blockage of the break in the vasculature. As such, platelet plug formation occurs after vasoconstriction of the blood vessels but before the creation of the fibrin mesh clot, which is the more permanent solution to the injury. The result of the platelet plug formation
1700-442: A radius of 10 Å (1.0 nm). According to another study, when measured in a different solution, the DNA chain measured 22–26 Å (2.2–2.6 nm) wide, and one nucleotide unit measured 3.3 Å (0.33 nm) long. The buoyant density of most DNA is 1.7g/cm . DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. These two long strands coil around each other, in
1800-416: A second protein when read in the opposite direction along the other strand. In bacteria , this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome. DNA can be twisted like a rope in a process called DNA supercoiling . With DNA in its "relaxed" state, a strand usually circles
1900-445: A simple TTAGGG sequence. These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases, known as a guanine tetrad , form a flat plate. These flat four-base units then stack on top of each other to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between
2000-413: Is a polymer composed of two polynucleotide chains that coil around each other to form a double helix . The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses . DNA and ribonucleic acid (RNA) are nucleic acids . Alongside proteins , lipids and complex carbohydrates ( polysaccharides ), nucleic acids are one of
2100-758: Is a protein on the surface of the platelet membrane that binds to vWF. When vWF is bound to glycoprotein lb, it helps the platelet interact with other surfaces, like the inside of a damaged vessel wall. At high shear stress levels, the GP1b-von Willebrand Factor will initiate the platelet adhesion. This process will then be mediated by integrins, such as β1 (α2β1, α5β1) and β3 (αIIbβ3) integrins. In addition, platelets are activated, they will also change shape in their cortical actin cytoskeleton. The platelets will transform from smooth, biconcave discs to fully spread cells. This dramatically increases their surface area and therefore allows for both increased blockage of
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#17328590978582200-449: Is activated when it binds to PGI 2 . This activation, in turn, signals adenylyl cyclase to produce cAMP . cAMP goes on to inhibit any undue platelet activation (in order to promote circulation) and also counteracts any increase in cytosolic calcium levels that would result from thromboxane A2 (TXA 2 ) binding (leading to platelet activation and subsequent coagulation ). PGI 2 also binds to endothelial prostacyclin receptors , and in
2300-447: Is called intercalation . Most intercalators are aromatic and planar molecules; examples include ethidium bromide , acridines , daunomycin , and doxorubicin . For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens , and in
2400-435: Is called a polynucleotide . The backbone of the DNA strand is made from alternating phosphate and sugar groups. The sugar in DNA is 2-deoxyribose , which is a pentose (five- carbon ) sugar. The sugars are joined by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons,
2500-399: Is completely reversed after 25 minutes. No evidence of platelet dysfunction or an increase in surgical bleeding after administration of inhaled epoprostenol has been found. The drug has been known to cause flushing, headaches and hypotension. Prostacyclin is produced in endothelial cells , which line the walls of arteries and veins, from prostaglandin H 2 (PGH 2 ) by the action of
2600-434: Is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC -content have more strongly interacting strands, while short helices with high AT content have more weakly interacting strands. In biology, parts of
2700-444: Is desired. As such, the platelets in the plasma must be alerted to the need for a plug formation. Any discontinuity detected in the vascular endothelium triggers an automatic response in the clotting system, which in turns stimulates thrombin production. Thrombin also causes platelet aggregation. As such, more often than not, platelet adhesion and activation occur in overlapping steps, where one directly influences and contributes to
2800-536: Is explained by understanding the cells that produce each molecule, TXA 2 and PGI 2 . Since PGI 2 is primarily produced in a nucleated endothelial cell, the COX inhibition by NSAID can be overcome with time by increased COX gene activation and subsequent production of more COX enzymes to catalyze the formation of PGI 2 . In contrast, TXA 2 is released primarily by anucleated platelets, which are unable to respond to NSAID COX inhibition with additional transcription of
2900-426: Is formed after the temporary blockage is created. This process involves the conversion of fibrinogen, a soluble glycoprotein, into fibrin , an insoluble glycoprotein, using the enzyme thrombin . The fibrinogen forms fibrin to encase the platelet thrombus, thus creating a secondary hemostatic plug that is much more stable and securely attached to the vessel wall. Due to the shear force, a platelet thrombus attached to
3000-411: Is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin . Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in
3100-667: Is inhibited by the action of NSAIDs on cyclooxygenase enzymes COX1 and COX2. These convert arachidonic acid to prostaglandin H2 (PGH 2 ), the immediate precursor of prostacyclin. Since thromboxane (an eicosanoid stimulator of platelet aggregation) is also downstream of COX enzymes, one might think that the effect of NSAIDs would act to balance. However, prostacyclin concentrations recover much faster than thromboxane levels, so aspirin administration initially has little to no effect but eventually prevents platelet aggregation (the effect of prostaglandins predominates as they are regenerated). This
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3200-432: Is introduced by enzymes called topoisomerases . These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication . DNA exists in many possible conformations that include A-DNA , B-DNA , and Z-DNA forms, although only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on
3300-422: Is nothing special about the four natural nucleobases that evolved on Earth. On the other hand, DNA is tightly related to RNA which does not only act as a transcript of DNA but also performs as molecular machines many tasks in cells. For this purpose it has to fold into a structure. It has been shown that to allow to create all possible structures at least four bases are required for the corresponding RNA , while
3400-432: Is one of four types of nucleobases (or bases ). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription , where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U). Under the genetic code , these RNA strands specify
3500-514: Is rarely used). The stability of the dsDNA form depends not only on the GC -content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the melting temperature (also called T m value), which is the temperature at which 50% of the double-strand molecules are converted to single-strand molecules; melting temperature
3600-428: Is recreated by an enzyme called DNA polymerase . This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on
3700-451: Is the coagulation of blood. It can also be referred to as primary hemostasis. For many years, the critical role that platelets (also known as thrombocytes) played in hemostasis and blood coagulation went unnoticed by scientists. Even though the existence of platelets as a cell fragment was initially discovered in 1882, it took scientists until the 1960s before they moved their interest from the interaction of platelets with blood coagulation to
3800-516: Is the largest human chromosome with approximately 220 million base pairs , and would be 85 mm long if straightened. In eukaryotes , in addition to nuclear DNA , there is also mitochondrial DNA (mtDNA) which encodes certain proteins used by the mitochondria. The mtDNA is usually relatively small in comparison to the nuclear DNA. For example, the human mitochondrial DNA forms closed circular molecules, each of which contains 16,569 DNA base pairs, with each such molecule normally containing
3900-486: Is to allow the cell to replicate chromosome ends using the enzyme telomerase , as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells , telomeres are usually lengths of single-stranded DNA containing several thousand repeats of
4000-513: Is to prepare prostacyclin in alkaline buffer. Even at physiological pH, prostacyclin can rapidly form the inactive hydration product 6-keto-prostaglandin F1α . As mentioned above, prostacyclin (PGI 2 ) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor ( prostacyclin receptor )
4100-657: The DNA sequence . Mutagens include oxidizing agents , alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays . The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers , which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions,
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4200-406: The amino-acid sequences of proteins is determined by the rules of translation , known collectively as the genetic code . The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase . This RNA copy is then decoded by a ribosome that reads
4300-469: The cell nucleus as nuclear DNA , and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA . In contrast, prokaryotes ( bacteria and archaea ) store their DNA only in the cytoplasm , in circular chromosomes . Within eukaryotic chromosomes, chromatin proteins, such as histones , compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of
4400-401: The enzyme prostacyclin synthase . Although prostacyclin is considered an independent mediator, it is called PGI 2 (prostaglandin I 2 ) in eicosanoid nomenclature, and is a member of the prostanoids (together with the prostaglandins and thromboxane ). PGI 2 , derived primarily from COX-2 in humans, is the major arachidonate metabolite released from the vascular endothelium. This is
4500-419: The 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix , the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel . The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with
4600-588: The 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ribose in RNA. The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine ( A ), cytosine ( C ), guanine ( G ) and thymine ( T ). These four bases are attached to
4700-470: The COX gene because they lack DNA material necessary to perform such a task. This allows NSAIDs to result in PGI 2 dominance that promotes circulation and retards thrombosis . In patients with pulmonary hypertension , inhaled epoprostenol reduces pulmonary pressure, and improves right ventricular stroke volume in patients undergoing cardiac surgery. A dose of 60 μg is hemodynamically safe, and its effect
4800-435: The DNA are transcribed. DNA is a long polymer made from repeating units called nucleotides . The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds . Both chains are coiled around the same axis, and have the same pitch of 34 ångströms (3.4 nm ). The pair of chains have
4900-453: The DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters , tend to have a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the melting temperature T m necessary to break half of the hydrogen bonds. When all the base pairs in a DNA double helix melt,
5000-401: The RNA sequence by base-pairing the messenger RNA to transfer RNA , which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (4 combinations). These encode the twenty standard amino acids , giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are
5100-488: The TAG, TAA, and TGA codons, (UAG, UAA, and UGA on the mRNA). Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication . Here, the two strands are separated and then each strand's complementary DNA sequence
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#17328590978585200-442: The axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that
5300-406: The binding of the adhesive platelets with vWF and fibrinogen. ADP can then catalyze the aggregation of platelets, allowing for fibrinogen to link two platelets together. As more platelets accumulate, they release more chemicals, which in turn attract even more platelets. This is a positive feedback loop that eventually results in the formation of the platelet thrombus. A secondary hemostatic plug
5400-409: The blood vessel's walls can easily be swept away or disintegrated. As such, after the platelets have been anchored to the vessel wall, have been linked together, and have been enmeshed in fibrin, they must also be consolidated to ensure they can withstand such force. This is accomplished by factor XIII , also known as fibrin stabilizing factor, an enzyme that crosslinks fibrin. Factor XIII is critical in
5500-407: The canonical bases plus uracil. Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site . As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. The major groove is 22 ångströms (2.2 nm) wide, while
5600-467: The case of thalidomide, a teratogen . Others such as benzo[ a ]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells. DNA usually occurs as linear chromosomes in eukaryotes , and circular chromosomes in prokaryotes . The set of chromosomes in
5700-581: The cell (see below) , but the major and minor grooves are always named to reflect the differences in width that would be seen if the DNA was twisted back into the ordinary B form . In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing . Purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across
5800-619: The chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling ). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression. For one example, cytosine methylation produces 5-methylcytosine , which is important for X-inactivation of chromosomes. The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite
5900-476: The conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder. Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and
6000-497: The consolidation of a hemostatic plug. Those who are found to be deficient in the enzyme exhibit delayed bleeding after surgical procedures. While platelet activation and plug formation are necessary for the cessation of bleeding and vascular injuries, if platelet adhesion and aggregation occur in an unwarranted location, the result will instead be vascular obstruction and thrombosis. This is commonly observed in myocardial infarctions, in which platelet aggregation and adhesion result in
6100-405: The creation of new genes through the process of gene duplication and divergence . A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and
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#17328590978586200-449: The cytoplasm called the nucleoid . The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype . A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers , which control transcription of
6300-430: The damaged cells as well as more space for adhesion to occur. After platelets make contact with the focal point of the vascular injury, they begin to interact with each other to form a platelet aggregate. Platelet aggregation is mainly mediated by β3 (αIIbβ3) integrin and its ligands, such as vWF and fibrinogen. While platelet membranes have binding sites for fibrinogen, they must be induced by thrombin. Thrombin triggers
6400-458: The dense granules, serotonin and adenosine diphosphate are released. From the alpha granules come molecules such as the platelet-derived growth factor, fibrinogen, and the von Willebrand factor (vWF), a glycoprotein critical in platelet activation and adhesion. The ADP secreted from the dense granules then binds to receptors on the membrane of platelets. However, to allow for platelet adhesion to occur requires an additional molecule. Glycoprotein lb
6500-405: The double helix (from six-carbon ring to six-carbon ring) is called a Watson-Crick base pair. DNA with high GC-content is more stable than DNA with low GC -content. A Hoogsteen base pair (hydrogen bonding the 6-carbon ring to the 5-carbon ring) is a rare variation of base-pairing. As hydrogen bonds are not covalent , they can be broken and rejoined relatively easily. The two strands of DNA in
6600-442: The edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure. In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here,
6700-481: The end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see
6800-462: The first paper on prostacyclin in Nature . The collaboration produced a synthesized molecule, which was named epoprostenol. But, as with native prostacyclin, the epoprostenol molecule is unstable in solution and prone to rapid degradation. This presented a challenge for both in vitro experiments and clinical applications. To overcome this challenge, the research team that discovered prostacyclin continued
6900-418: The focus is on the interactions between DNA and other molecules that mediate the function of the genome. Genomic DNA is tightly and orderly packed in the process called DNA condensation , to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus , with small amounts in mitochondria and chloroplasts . In prokaryotes, the DNA is held within an irregularly shaped body in
7000-461: The four major types of macromolecules that are essential for all known forms of life . The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides . Each nucleotide is composed of one of four nitrogen-containing nucleobases ( cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose , and a phosphate group . The nucleotides are joined to one another in
7100-448: The functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing. A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses , blur the distinction between sense and antisense strands by having overlapping genes . In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and
7200-448: The helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription. For many years, exobiologists have proposed the existence of a shadow biosphere , a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of
7300-448: The hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions , and the presence of polyamines in solution. The first published reports of A-DNA X-ray diffraction patterns —and also B-DNA—used analyses based on Patterson functions that provided only a limited amount of structural information for oriented fibers of DNA. An alternative analysis
7400-427: The hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging. Many mutagens fit into the space between two adjacent base pairs, this
7500-412: The importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations . Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain , and the glycosylation of uracil to produce the "J-base" in kinetoplastids . DNA can be damaged by many sorts of mutagens , which change
7600-436: The interaction of platelets with themselves. The discovery of adenosine diphosphate (ADP) as the primary inducer of platelet aggregation was a major breakthrough in the field of hematology. It was followed by the discovery of the platelet release reaction, as well as the aggregating properties of thrombin and collagen . The platelet plug formation is the second step of hemostasis. It occurs after vasoconstriction. During
7700-441: The minor groove is 12 Å (1.2 nm) in width. Due to the larger width of the major groove, the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within
7800-516: The mitochondrial genome (constituting up to 90% of the DNA of the cell). A DNA sequence is called a "sense" sequence if it is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but
7900-477: The most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations , insertions , deletions from the DNA sequence, and chromosomal translocations . These mutations can cause cancer . Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. DNA damages that are naturally occurring , due to normal cellular processes that produce reactive oxygen species,
8000-464: The new strand, and the cell ends up with a perfect copy of its DNA. Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer ; it may provide nutrients; and it may act as
8100-454: The open reading frame. In many species , only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons , with over 50% of human DNA consisting of non-coding repetitive sequences . The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size , or C-value , among species, represent
8200-434: The other. Once platelets are activated, when they come across injured endothelium cells, the von Willebrand factor (vWF) and fibrinogen will act as anchors to allow platelets to adhere onto the vessel wall. These molecules are released from the platelet themselves as a result of degranulation, a physiological change in the platelet's shape due to the secretion of the contents of the dense granules and alpha granules. From
8300-428: The place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology. Modified bases occur in DNA. The first of these recognized was 5-methylcytosine , which was found in the genome of Mycobacterium tuberculosis in 1925. The reason for
8400-530: The presence of these noncanonical bases in bacterial viruses ( bacteriophages ) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses. Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the epigenetic control of gene expression in plants and animals. A number of noncanonical bases are known to occur in DNA. Most of these are modifications of
8500-412: The prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond . Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of
8600-435: The process, platelets begin to accumulate, or aggregate, on the damaged vessel wall. Platelet plug formation occurs in three major steps: Under normal physiological conditions, blood flows through the body without any noticeable aggregation of platelets. This is because platelets are not initially programmed to accumulate by themselves because this could cause an undesirable thrombosis. However, during hemostasis, coagulation
8700-466: The proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA . A report in 2010 of the possibility in the bacterium GFAJ-1 was announced, though the research was disputed, and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules. At the ends of the linear chromosomes are specialized regions of DNA called telomeres . The main function of these regions
8800-458: The research. The research team synthesized nearly 1,000 analogues. Platelet plug The platelet plug, also known as the hemostatic plug or platelet thrombus , is an aggregation of platelets formed during early stages of hemostasis in response to one or more injuries to blood vessel walls . After platelets are recruited and begin to accumulate around the breakage, their “sticky” nature allows them to adhere to each other. This forms
8900-486: The role of prostaglandins in anaphylaxis and respiratory diseases. Working with a team from the Royal College of Surgeons , Vane discovered that aspirin and other oral anti-inflammatory drugs work by inhibiting the synthesis of prostaglandins. This critical finding opened the door to a broader understanding of the role of prostaglandins in the body. A team at The Wellcome Foundation led by Salvador Moncada had identified
9000-530: The role they play. Fibrinogen and vWF are known critical factors in hemostasis. However, it has been discovered that even in mice who lack both of these components, hemostasis and thrombosis still occur. This seems to suggest that there are other contributing molecules still undiscovered that may also play an important role in platelet aggregation and adhesion. DNA Deoxyribonucleic acid ( / d iː ˈ ɒ k s ɪ ˌ r aɪ b oʊ nj uː ˌ k l iː ɪ k , - ˌ k l eɪ -/ ; DNA )
9100-517: The same manner, raises cAMP levels in the cytosol. This cAMP then goes on to activate protein kinase A (PKA). PKA then continues the cascade by promoting the phosphorylation of the myosin light chain kinase , which inhibits it and leads to smooth muscle relaxation and vasodilation . It can be noted that PGI 2 and TXA 2 work as physiological antagonists. Synthetic prostacyclin analogues ( iloprost , cisaprost) are used intravenously, subcutaneously or by inhalation: The production of prostacyclin
9200-432: The section on uses in technology below. Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA . Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence could be seen as an indication that there
9300-431: The sequence of amino acids within proteins in a process called translation . Within eukaryotic cells, DNA is organized into long structures called chromosomes . Before typical cell division , these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms ( animals , plants , fungi and protists ) store most of their DNA inside
9400-473: The shape of a double helix . The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside , and a base linked to a sugar and to one or more phosphate groups is called a nucleotide . A biopolymer comprising multiple linked nucleotides (as in DNA)
9500-552: The single-ringed pyrimidines and the double-ringed purines . In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine. Both strands of double-stranded DNA store the same biological information . This information is replicated when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding , meaning that these sections do not serve as patterns for protein sequences . The two strands of DNA run in opposite directions to each other and are thus antiparallel . Attached to each sugar
9600-498: The single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop . In DNA, fraying occurs when non-complementary regions exist at
9700-518: The strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others. In humans, the total female diploid nuclear genome per cell extends for 6.37 Gigabase pairs (Gbp), is 208.23 cm long and weighs 6.51 picograms (pg). Male values are 6.27 Gbp, 205.00 cm, 6.41 pg. Each DNA polymer can contain hundreds of millions of nucleotides, such as in chromosome 1 . Chromosome 1
9800-469: The sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate . Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs . The nucleobases are classified into two types: the purines , A and G , which are fused five- and six-membered heterocyclic compounds , and the pyrimidines , the six-membered rings C and T . A fifth pyrimidine nucleobase, uracil ( U ), usually takes
9900-434: The ω-3 EPA . Prostacyclin can be synthesized from the methyl ester of prostaglandin F 2α . After its synthesis, the drug is reconstituted in saline and glycerin. Because prostacyclin is so chemically labile, quantitation of their inactive metabolites, rather than the active compounds, is used to assess their rate of synthesis. During the 1960s, a UK research team, headed by Professor John Vane , began to explore
10000-517: Was proposed by Wilkins et al. in 1953 for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions . In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double helix. Although the B-DNA form is most common under
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