12-hete

12-HETE ((±)12-HETE) 是 PGE2 的调节因子，具有抗血栓形成和促血栓形成作用，通过蛇毒 IIA 组磷脂酶 A2 诱导诱导 PGE2 释放和 COX-2 表达。12-HETE 还是一种神经调节剂，通过激活 NADPH 氧化酶和随后的生成激活视网膜细胞，诱导糖尿病视网膜病变的内皮功能障碍。

12(S)-HETE 是花生四烯酸的12-脂氧合酶代谢产物，对癌细胞增殖具有促有丝分裂作用，可增强血管紧张素 II 诱导的 BLT2 收缩（白三烯 B4小鼠动脉中 2 型受体）和 TP （血栓素受体） 介导的机制。12(S)-HETE促进动脉内皮细胞中超氧化物和异血栓素样代谢物的产生。

Biosynthesis of 12(R)-HETE in invertebrates is via lipoxygenation of arachidonic acid . In mammals, 12(R)-HETE can be produced by 12(R)-LOs and also by CYP450 oxidation. The activity of 12(R)-HETE in mammals is predominantly proinflammatory. 12(R)-HETE exhibits dose-dependent leukocyte chemotaxis at concentrations as low as 100 nM, and lowers intraocular pressure in rabbits.

12(S)-HETE is a product of arachidonic acid metabolism through the 12-lipoxygenase pathway. It is primarily found in platelets, leukocytes, and to a lesser extent in smooth muscle cells. It enhances tumor cell adhesion to endothelial cells, fibronectin, and the subendothelial matrix. tetranor-12(S)-HETE is the major β-oxidation product resulting from peroxisomal metabolism of 12(S)-HETE in numerous tissues, and Lewis lung carcinoma cells. No biological function has yet been determined for tetranor-12(S)-HETE. Some data indicate it may play a role in controlling the inflammatory response in injured corneas. In some diseases (e.g., Zellweger's Syndrome) peroxisomal abnormalities result in the inability of cells to metabolize 12(S)-HETE, which may be responsible for symptoms of the disease. The tetranor derivative of 12(S)-HETE is available as a research tool for the elucidation of the metabolic fate of its parent compound.

Metabolism of 12(R)-HETE in corneal tissue produces predominantly the compound resulting from the loss of four carbon atoms through β-oxidation from C-1. This metabolite is 8(R)-hydroxy hexadecatrienoic acid (8(R)-HHxTrE) or 2,3,4,5-tetranor 12(R)-HETE.

(±)12-HEPE is produced by non-enzymatic oxidation of EPA. It contains equal amounts of 12(S)-HEPE and 12(R)-HEPE. The biological activity of (±)12-HEPE is likely mediated by one of the individual isomers, most commonly the 12(S) isomer in mammalian systems. 12-HEPE inhibits platelet aggregation with the same potency as 12-HETE, exhibiting IC50 values of 24 and 25 µM, respectively. [1] These compounds are also equipotent as inhibitors of U46619-induced contraction of rat aorta (IC50s = 8.6-8.8 µM).[2]

N-Arachidonoyl taurine is an arachidonoyl amino acid. It is oxygenated by 12(S)- and 15(S)-lipoxygenase and is converted to 12-HETE-taurine (12-HETE-T) in murine resident peritoneal macrophages. N-Arachidonoyl taurine is an activator of the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 (EC50s = 28 and 21 μM, respectively). It increases calcium flux in HIT-T15 pancreatic β-cells and INS-1 rat islet cells when used at a concentration of 10 μM and increases insulin secretion from 832 13 INS-1 pancreatic β-cells. The levels of N-arachidonoyl taurine are changed in mouse brain following administration of δ9-tetrahydrocannabinol (δ9-THC).

9(S)-HETE is an enantiomer which makes up 50% of (±)9-HETE . There are no reports of 9(S)-HETE occurring as an enzymatic lipoxygenation product. Whereas 12(S)-HETE promotes adhesion of several cell lines to endothelial cell monolayes, 9(S)-HETE and other positional HETEs are without effect. Stereochemical assignment of the (S) enantiomer is based on comparison of chiral HPLC retention times to published results.

5(S),12(S)-DiHETE is a natural bioactive lipid derived from arachidonic acid . It is synthesized by glycogen-induced rabbit peritoneal polymorphonuclear leukocytes (PMNLs) incubated with AA. 5(S),12(S)-DiHETE can be produced by successive oxygenation of AA by 5-lipoxygenase (5-LO) in platelets and 12-LO in leukocytes. It can also be synthesized from 12(S)-HETE by 5-LO, in the presence of 5-LO activating protein (FLAP), activated with calcium ionophore. 5(S),12(S)-DiHETE is an epimer of leukotriene B4 that is weakly chemotactic for PMNL.

12(S)-HpETE（12-羟基二十碳四烯酸）是花生四烯酸在12-脂氧合酶（12-LOX）作用下生成的过氧化代谢产物。​能剂量依赖性地刺激细胞内Ca2+释放（效用低于12-HETE），还能通过其对内皮细胞的作用参与血管张力的调节，诱导血管平滑肌细胞c-Fos和c-Jun蛋白的表达，增加AP-1（ activating protein 1）的活性。

Lobaric acid is a depsidone metabolite that has been isolated from Stereocaulon lichen species with antioxidant, antiproliferative, antiviral, and enzyme inhibitory activites. It scavenges superoxide radicals in a cell-free assay (IC50 = 97.9 μmol) and inhibits proliferation in a panel of leukemia, colorectal, gastric, breast, ovarian, prostate, pancreatic, and lung cancer cell lines (EC50s = 15.2-63.9 μg ml). Lobaric acid inhibits protein tyrosine phosphatase 1B (PTP1B; IC50 = 0.87 μM for the human recombinant enzyme) and production of 12(S)-HETE (Item No. 34570) by 12(S)-lipoxygenase (IC50 = 28.5 μM). In vivo, lobaric acid (250 μM) decreases lesion number, but not lesion diameter, in tobacco leaves infected with tobacco mosaic virus (TMV).

12(R)-HEPE, a monohydroxy fatty acid derived from EPA in the eggs of the sea urchin S. purpuratus, has a biological activity that, while not extensively documented, may resemble that of 12(R)-HETE (Catalog No.34560).

Mulberrofuran A can inhibit the formations of 12-hydroxy-, 8, 10-heptadecatrienoic acid (HHT) and thromboxane B2, but it can increase the formation of 12-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (12-HETE).