Reaction Process: Reactome:R-OSA-2142712
Synthesis of 12-eicosatetraenoic acid derivatives related metabolites
find 6 related metabolites which is associated with chemical reaction(pathway) Synthesis of 12-eicosatetraenoic acid derivatives
AA + Oxygen ⟶ 12R-HpETE
Arachidonic acid
Arachidonic acid is a polyunsaturated, essential fatty acid that has a 20-carbon chain as a backbone and four cis-double bonds at the C5, C8, C11, and C14 positions. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is synthesized from dietary linoleic acid. Arachidonic acid mediates inflammation and the functioning of several organs and systems either directly or upon its conversion into eicosanoids. Arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. Arachidonic acid can be metabolized by cytochrome p450 (CYP450) enzymes into 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs), their corresponding dihydroxyeicosatrienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE). The production of kidney CYP450 arachidonic acid metabolites is altered in diabetes, pregnancy, hepatorenal syndrome, and in various models of hypertension, and it is likely that changes in this system contribute to the abnormalities in renal function that are associated with many of these conditions. Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (PMID: 12736897, 12736897, 12700820, 12570747, 12432908). The beneficial effects of omega-3 fatty acids are believed to be due in part to selective alteration of arachidonate metabolism that involves cyclooxygenase (COX) enzymes (PMID: 23371504). 9-Oxononanoic acid (9-ONA), one of the major products of peroxidized fatty acids, was found to stimulate the activity of phospholipase A2 (PLA2), the key enzyme to initiate the arachidonate cascade and eicosanoid production (PMID: 23704812). Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases (PMID: 23404351). Essential fatty acid. Constituent of many animal phospholipids Arachidonic acid. CAS Common Chemistry. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=506-32-1 (retrieved 2024-07-15) (CAS RN: 506-32-1). Licensed under the Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0). Arachidonic acid is an essential fatty acid and a major constituent of biomembranes. Arachidonic acid is an essential fatty acid and a major constituent of biomembranes.
12(S)-HPETE
12-HPETE is one of the six monohydroperoxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid (Leukotrienes). Reduction of the hydroperoxide yields the more stable hydroxyl fatty acid (+/-)12-HETE. A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. 12-HPETE is one of the six monohydroperoxy fatty acids produced by the non-enzymatic oxidation of arachidonic acid (Leukotrienes). Reduction of the hydroperoxide yields the more stable hydroxyl fatty acid (+/-)12-HETE. D006401 - Hematologic Agents > D010975 - Platelet Aggregation Inhibitors D002317 - Cardiovascular Agents > D014662 - Vasoconstrictor Agents
Oxygen
Oxygen is the third most abundant element in the universe after hydrogen and helium and the most abundant element by mass in the Earths crust. Diatomic oxygen gas constitutes 20.9\\% of the volume of air. All major classes of structural molecules in living organisms, such as proteins, carbohydrates, and fats, contain oxygen, as do the major inorganic compounds that comprise animal shells, teeth, and bone. Oxygen in the form of O2 is produced from water by cyanobacteria, algae and plants during photosynthesis and is used in cellular respiration for all living organisms. Green algae and cyanobacteria in marine environments provide about 70\\% of the free oxygen produced on earth and the rest is produced by terrestrial plants. Oxygen is used in mitochondria to help generate adenosine triphosphate (ATP) during oxidative phosphorylation. For animals, a constant supply of oxygen is indispensable for cardiac viability and function. To meet this demand, an adult human, at rest, inhales 1.8 to 2.4 grams of oxygen per minute. This amounts to more than 6 billion tonnes of oxygen inhaled by humanity per year. At a resting pulse rate, the heart consumes approximately 8-15 ml O2/min/100 g tissue. This is significantly more than that consumed by the brain (approximately 3 ml O2/min/100 g tissue) and can increase to more than 70 ml O2/min/100 g myocardial tissue during vigorous exercise. As a general rule, mammalian heart muscle cannot produce enough energy under anaerobic conditions to maintain essential cellular processes; thus, a constant supply of oxygen is indispensable to sustain cardiac function and viability. However, the role of oxygen and oxygen-associated processes in living systems is complex, and they and can be either beneficial or contribute to cardiac dysfunction and death (through reactive oxygen species). Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that are produced in mammalian cells under normal and pathologic conditions. Many ROS, such as the superoxide anion (O2-)and hydrogen peroxide (H2O2), act within blood vessels, altering mechanisms mediating mechanical signal transduction and autoregulation of cerebral blood flow. Reactive oxygen species are believed to be involved in cellular signaling in blood vessels in both normal and pathologic states. The major pathway for the production of ROS is by way of the one-electron reduction of molecular oxygen to form an oxygen radical, the superoxide anion (O2-). Within the vasculature there are several enzymatic sources of O2-, including xanthine oxidase, the mitochondrial electron transport chain, and nitric oxide (NO) synthases. Studies in recent years, however, suggest that the major contributor to O2- levels in vascular cells is the membrane-bound enzyme NADPH-oxidase. Produced O2- can react with other radicals, such as NO, or spontaneously dismutate to produce hydrogen peroxide (H2O2). In cells, the latter reaction is an important pathway for normal O2- breakdown and is usually catalyzed by the enzyme superoxide dismutase (SOD). Once formed, H2O2 can undergo various reactions, both enzymatic and nonenzymatic. The antioxidant enzymes catalase and glutathione peroxidase act to limit ROS accumulation within cells by breaking down H2O2 to H2O. Metabolism of H2O2 can also produce other, more damaging ROS. For example, the endogenous enzyme myeloperoxidase uses H2O2 as a substrate to form the highly reactive compound hypochlorous acid. Alternatively, H2O2 can undergo Fenton or Haber-Weiss chemistry, reacting with Fe2+/Fe3+ ions to form toxic hydroxyl radicals (-.OH). (PMID: 17027622, 15765131) [HMDB]. Oxygen is found in many foods, some of which are soy bean, watermelon, sweet basil, and spinach. Oxygen is the third most abundant element in the universe after hydrogen and helium and the most abundant element by mass in the Earths crust. Diatomic oxygen gas constitutes 20.9\\% of the volume of air. All major classes of structural molecules in living organisms, such as proteins, carbohydrates, and fats, contain oxygen, as do the major inorganic compounds that comprise animal shells, teeth, and bone. Oxygen in the form of O2 is produced from water by cyanobacteria, algae and plants during photosynthesis and is used in cellular respiration for all living organisms. Green algae and cyanobacteria in marine environments provide about 70\\% of the free oxygen produced on earth and the rest is produced by terrestrial plants. Oxygen is used in mitochondria to help generate adenosine triphosphate (ATP) during oxidative phosphorylation. For animals, a constant supply of oxygen is indispensable for cardiac viability and function. To meet this demand, an adult human, at rest, inhales 1.8 to 2.4 grams of oxygen per minute. This amounts to more than 6 billion tonnes of oxygen inhaled by humanity per year. At a resting pulse rate, the heart consumes approximately 8-15 ml O2/min/100 g tissue. This is significantly more than that consumed by the brain (approximately 3 ml O2/min/100 g tissue) and can increase to more than 70 ml O2/min/100 g myocardial tissue during vigorous exercise. As a general rule, mammalian heart muscle cannot produce enough energy under anaerobic conditions to maintain essential cellular processes; thus, a constant supply of oxygen is indispensable to sustain cardiac function and viability. However, the role of oxygen and oxygen-associated processes in living systems is complex, and they and can be either beneficial or contribute to cardiac dysfunction and death (through reactive oxygen species). Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that are produced in mammalian cells under normal and pathologic conditions. Many ROS, such as the superoxide anion (O2-)and hydrogen peroxide (H2O2), act within blood vessels, altering mechanisms mediating mechanical signal transduction and autoregulation of cerebral blood flow. Reactive oxygen species are believed to be involved in cellular signaling in blood vessels in both normal and pathologic states. The major pathway for the production of ROS is by way of the one-electron reduction of molecular oxygen to form an oxygen radical, the superoxide anion (O2-). Within the vasculature there are several enzymatic sources of O2-, including xanthine oxidase, the mitochondrial electron transport chain, and nitric oxide (NO) synthases. Studies in recent years, however, suggest that the major contributor to O2- levels in vascular cells is the membrane-bound enzyme NADPH-oxidase. Produced O2- can react with other radicals, such as NO, or spontaneously dismutate to produce hydrogen peroxide (H2O2). In cells, the latter reaction is an important pathway for normal O2- breakdown and is usually catalyzed by the enzyme superoxide dismutase (SOD). Once formed, H2O2 can undergo various reactions, both enzymatic and nonenzymatic. The antioxidant enzymes catalase and glutathione peroxidase act to limit ROS accumulation within cells by breaking down H2O2 to H2O. Metabolism of H2O2 can also produce other, more damaging ROS. For example, the endogenous enzyme myeloperoxidase uses H2O2 as a substrate to form the highly reactive compound hypochlorous acid. Alternatively, H2O2 can undergo Fenton or Haber-Weiss chemistry, reacting with Fe2+/Fe3+ ions to form toxic hydroxyl radicals (-.OH). (PMID: 17027622, 15765131). V - Various > V03 - All other therapeutic products > V03A - All other therapeutic products > V03AN - Medical gases
Hepoxilin A3
Hepoxilin A3 is an electrophilic eicosanoids synthesized during arachidonic acid oxidative metabolism, which can participate in the Michael addition reaction with glutathione (GSH, a major cellular antioxidant) catalyzed by the GSH-S-transferase (GST) family. GSH-adducts have been observed with molecules synthesized through the 12-lipoxygenase pathway. (PMID 12432937). Hepoxilins have biological actions that appear to have, as their basis, changes in intracellular concentrations of ions including calcium and potassium ions as well as changes in second messenger systems. Recent evidence suggests that the biological actions of the hepoxilins may be receptor-mediated as indicated from data showing the existence of hepoxilin-specific binding proteins in the human neutrophils. Such evidence also implicates the association of G-proteins both in hepoxilin-binding as well as in hepoxilin action. (PMID 7947989). Hepoxilin A3 is an electrophilic eicosanoids synthesized during arachidonic acid oxidative metabolism, which can participate in the Michael addition reaction with glutathione (GSH, a major cellular antioxidant) catalyzed by the GSH-S-transferase (GST) family. GSH-adducts have been observed with molecules synthesized through the 12-lipoxygenase pathway. (PMID 12432937)
12(R)-HPETE
12(R)-HPETE is a hydroperoxyeicosatetraenoic acid eicosanoid derived from arachidonic acid. The epidermal lipoxygenases 12R-LOX and eLOX3 act in sequence to convert arachidonic acid via 12(R)-HPETE to 12(R)-HETE and the corresponding epoxyalcohol, 8(R)-hydroxy-11(R),12(R)-epoxyeicosatrienoic acid. The epidermal lipoxygenases 12R-LOX and eLOX3 are the gene products of ALOX12B and ALOXE3. Mutations in ALOXE3 or ALOX12B have been found in families with autosomal-recessive congenital ichthyosis (ARCI). ARCI is a clinically and genetically heterogeneous group of severe hereditary keratinization disorders characterized by intense scaling of the whole integument, and differences in color and shape, often associated with erythema. Mutations in ALOXE3 and ALOX12B on chromosome 17p13, which code for two different epidermal lipoxygenases, were found in patients with ichthyosiform erythroderma. Genetic studies indicated that 12R-lipoxygenase (12R-LOX) or epidermal lipoxygenase-3 (eLOX3) was mutated in six families affected by non-bullous congenital ichthyosiform erythroderma (NCIE), one of the main clinical forms of ichthyosis. (PMID: 16116617, 15629692). 12(R)-HPETE is a hydroperoxyeicosatetraenoic acid eicosanoid derived from arachidonic acid. The epidermal lipoxygenases 12R-LOX and eLOX3 act in sequence to convert arachidonic acid via 12(R)-HPETE to 12(R)-HETE and the corresponding epoxyalcohol, 8(R)-hydroxy-11(R),12(R)-epoxyeicosatrienoic acid.
12-KETE
12-keto-eicosatetraenoic acid is a biologically active eicosanoid in the nervous system of Aplysia.It is a metabolite of 12-HPETE formed by Aplysia nervous tissue. 12-KETE was identified in incubations of the tissue with arachidonic acid using HPLC, UV spectrometry, and gas-chromatography/mass spectrometry. [3H]12-KETE is formed from endogenous lipid stores in nervous tissue, labeled with [3H]arachidonic acid upon stimulation by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine.[PMID:2774398] [HMDB] 12-keto-eicosatetraenoic acid is a biologically active eicosanoid in the nervous system of Aplysia.It is a metabolite of 12-HPETE formed by Aplysia nervous tissue. 12-KETE was identified in incubations of the tissue with arachidonic acid using HPLC, UV spectrometry, and gas-chromatography/mass spectrometry. [3H]12-KETE is formed from endogenous lipid stores in nervous tissue, labeled with [3H]arachidonic acid upon stimulation by application of histamine. In L14 and L10 cells, identified neurons in the abdominal ganglion, applications of 12-KETE elicit changes in membrane potential similar to those evoked by histamine.[PMID:2774398].