{"id":1849,"date":"2020-08-18T13:26:46","date_gmt":"2020-08-18T13:26:46","guid":{"rendered":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-pge12\/"},"modified":"2021-11-16T07:46:59","modified_gmt":"2021-11-16T05:46:59","slug":"synthesis-of-pge12","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-pge12\/","title":{"rendered":"Synthesis of PGE"},"content":{"rendered":"\n

Prostaglandins are local mediators. There are biogenic amines (histamine), peptides (bradykinin), proteins (cytokines), but prostaglandins and leukotrienes include eicosanoids too. These molecules are responsible for the generation of inflammation and for the proper blood coagulation too <\/div><\/p>\n\n\n\n
\"\"<\/a>
Figure 1. Synthesis of PGE<\/strong> <\/figcaption><\/figure><\/div>\n\n\n\n

These are oxidized derivatives of 20 C polyunsaturated fatty acids; their precursors are eicosatetraenoic acid (arachidonic acid) and pentanoic acid.<\/p>\n\n\n\n

Each cell can synthetise Prostanoids, but leukotrienes are less typycal.<\/p>\n\n\n\n

Arachidonic acid is synthesized from linoleic and linolenic acid, solely esterified in cells glycerophospholipids, if spontaneously released, is immediately esterified.\u00a0 When arachidonic acid released by PLA2<\/sub> (Role of the fatty acids<\/a>) by hydrolysis, which is determined by the calcium concentration rise (Figure 1<\/strong>).<\/p>\n\n\n\n

PLC results from PIP2<\/sub> (IP3<\/sub> and) DAG, from which the lipase cleaves arachidonic acid \u2014 this is important in platelets. Arachidonic acid can be removed from the cell, maybe reincorporated into phospholipids, but it can also be oxidized.<\/p>\n\n\n\n

Pathways<\/h2>\n<\/span>\n\n\n
  1. Cyclooxygenase (resulting in prostaglandins and thromboxanes)<\/strong><\/li>
  2. Lipoxygenases (leukotriene, PETE, HPETE)<\/li>
  3. Cytochrome p-450 epoxygenase (lipoxins, EET)<\/li><\/ol>\n\n\n<\/span>\n

    Cyclooxygenase (COX): membrane-bound enzymes are performed, primarily in ER.<\/h2>\n<\/span>\n\n\n
    \"\"<\/a>
    Figure 2. Synthesis of PGE<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

    The first step is deoxygenatio<\/strong>n; the cyclooxygenase enzyme builds two oxygen into the arachidonic acid to form the cyclopentane ring and PGG2<\/sub><\/strong>, a prostaglandin-endoperoxide is formed.<\/p>\n\n\n\n

    Its hydroperoxy group is reduced by hydroperoxidase, producing PGH2<\/sub><\/strong>.<\/p>\n\n\n\n

    The two enzymes together are the\u00a0prostaglandin endoperoxide synthetase<\/strong>.<\/p>\n\n\n\n

    • PGD2<\/sub>: PGH-PGD isomerase<\/li>
    • PGE2<\/sub>: PGH-PGE isomerase<\/li>
    • PGF2<\/sub>: PGH-PGF reductase or PGD and PGE<\/li>
    • PGI2<\/sub> (prostacyclin): prostacyclin synthase (intramolecular oxidoreduction)<\/li>
    • TXA2<\/sub> (thromboxane): thromboxane synthetase (intramolecular oxidoreduction)<\/li><\/ul>\n\n\n\n

      The latter two are cytochrome p450 enzymes. Prostanoid degradation occurs in the lung, kidney, and liver; cells are absorbed and inactivated.<\/p>\n\n\n\n

      The activity of cyclooxygenase is mediated by non-steroidal anti-inflammatory drugs, aspirin (serine acetylation). PGH2<\/sub> is a branching point, with various enzymes forming different prostanoids and thromboxanes (Figure 2<\/strong>).<\/p>\n\n\n<\/span>\n

      References<\/h2>\n<\/span>\n\n\n

      Snider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n<\/span>

      Pathways<\/h2>

      Cyclooxygenase (COX): membrane-bound enzymes are performed, primarily in ER.<\/h2>

      References<\/h2><\/div>","protected":false},"excerpt":{"rendered":"

      These are oxidized derivatives of 20 C polyunsaturated fatty acids; their precursors are eicosatetraenoic acid (arachidonic acid) and pentanoic acid. Each cell can synthetise Prostanoids, but leukotrienes are less typycal. Arachidonic acid is synthesized from linoleic and linolenic acid, solely esterified in cells glycerophospholipids, if spontaneously released, is immediately esterified.\u00a0 When arachidonic acid released by […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":1712,"menu_order":12,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1849","page","type-page","status-publish","hentry"],"yoast_head":"\nSynthesis of PGE – Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-pge12\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" 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