Biosynthesis

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

Release to cytoplasm or direct action in membrane

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

TJ v2i

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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