The biosynthetic mechanisms are reviewed in Figure 16-3. Succeeding reactions are catalyzed by glutathione-requiring isomerase, which is a GSH S-transferase, demonstrated to have A5-4-3-ketosteroid isomerase activity and requiring glutathione anion as a catalytic cofactor. The action of aspirin (acetylsalicylic
Effects on cell through membrane receptor
Modify membrane structure/ion movements/adenylate cyclase '-.-—' ♦
Cellular response Adenylate charge
FIGURE 16-5 Overview of PG and its relatives' syntheses and actions.
acid) or indomethacin is to acetylate the PG endoperoxide synthetase. This results in loss of the cyclooxygen-ase activity, but not the peroxidase activity. Apparently one acetylation per molecule of 68,000 Da is sufficient to complete the reaction and involves the hydroxyl group of a serine in the N-terminal portion (Figure 16-9).
A parallel set of reactions can be developed for substrates other than arachidonic acid. These reactions, pictured in Figure 16-10, account for PGE,, PGFW PGA!, and PGB:.
The leukotrienes (LT) derive from arachidonic acid, but do not proceed through a cyclic endoperoxide. Instead, this class of compounds derives by modification of arachidonic acid through the 5-lipoxygenase pathway or from other fatty acids, as shown in Figure 16-11. The three-dimensional structure of 15-lipoxy-genase from soybean has been solved, as shown in
FIGURE 16-6 The two conformers of PGF2„. The views are the projections on the planes defined by atoms C-12, C-15, and 0-15. Reproduced from Langs, D. A., Erman, M., and Detita, G. T. (1977). Science 197, 1003-1005. Copyright 1977 by the AAAS.
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Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.