Arachidonic acid

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  1. Arachidonic acid is formed from linoleic acid and linolenic acid, the only fatty acids known to be essential for complete nutrition
    1. Linoleic and linolenic acid are not synthesized in humans and must be supplied from the diet (oils from fish are a good source)
  2. arachidonic acid is released from membrane lipid of a cell by phospholipase A2 or a combination of phospholipase C and diglyceride lipase
  3. Arachidonic acid is metabolized by three main pathways:
    1. cyclooxygenase (cox) which makes prostaglandins and thromboxanes
      1. there are two cyclooxygenases: Cox I and Cox II (aspirin block more on Cox I while Celebrex and Vioxx block Cox II)
      2. prostacyclin - PGI2(one of the prostaglandins) is produced by vascular endothelial and smooth muscle cells and strongly inhibits platelet aggregation
      3. platelets release thromboxane A2 (TXA2) which contracts smooth muscle and induces platelet aggregation
    2. Cytochrome P450 which makes epoxides
    3. Lipoxygnase pathway forms hydroperoxyeicosatetranoic acids (HPETEs) and dihydroxyeicosatetraenoic acids 9DEA) subsequently converted to hydroxieicosatetraenoic acids(1)(HETEs)by peroxidases, (2) leukotrienes (LTC4) by hydrase and glutathione S-transferase (GST), and (3) lipoxins by lipoxygenases.
      1. metabolites of this pathway act as neurotransmitters (known to increase LH and LHRH from pituitary)
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