Arachidonic acid, an ω-6 FA that consists of 20 carbons and four double bonds, serves as the immediate precursor of the primary type of PG found in humans (series 2). These PGs contain two double bonds. Arachidonic acid is derived from linoleic acid, another ω-6 FA, through the process of elongation and desaturation. Within membrane phospholipids, typically phosphatidylinositol (PI), arachidonic acid is incorporated at carbon 2. It is then released from the membrane by phospholipase A2 in response to various signals, such as an increase in calcium.

PGH2 synthase (prostaglandin endoperoxide synthase), which consists of cyclooxygenase and peroxidase activities, is responsible for the initial step in the synthesis of PGs and TXs. This step involves the oxidative cyclization of free arachidonic acid to produce PGH2. PGH2 can further be converted to various PGs and TXs by specific synthases found in different cells. Notably, PGs contain a five-carbon ring, while TXs contain a heterocyclic six-membered oxane ring.

There are two isozymes of PGH2 synthase: COX-1 and COX-2. COX-1 is constitutively produced in most tissues and is essential for maintaining healthy gastric tissue, renal homeostasis, and platelet aggregation. On the other hand, COX-2 is inducible in a limited number of tissues and is stimulated by products released by activated immune and inflammatory cells. The induction of COX-2 leads to an increase in PG synthesis, which mediates the symptoms of inflammation (pain, heat, redness, and swelling) as well as the fever associated with infection.
Arachidonic acid, an ω-6 FA containing 20 carbons and four double bonds (an eicosatetraenoic FA), is the immediate precursor of the predominant type of human PG (series 2 or those with two double bonds, as shown in Fig. 17.22). It is derived by the elongation and desaturation of the essential FA linoleic acid, also an ω-6 FA. Arachidonic acid is incorporated into membrane phospholipids (typically PI) at carbon 2, from which it is released by phospholipase A2 (Fig. 17.23) in response to a variety of signals, such as a rise in calcium. [Note: Series 1 PG contain one double bond and are derived from an ω-6 eicosatrienoic FA, dihomo-γ-linolenic acid, whereas series 3 PG contain three double bonds and are derived from eicosapentaenoic acid (EPA), an ω-3 FA. See p. 363.] activities (cyclooxygenase and peroxidase) of PGH2 synthase (prostaglandin endoperoxide synthase). G-SH = reduced glutathione; G-S-S-G = oxidized glutathione; PG = prostaglandin.
1.
Prostaglandin H2 synthase: The first step in PG and TX synthesis is the oxidative cyclization of free arachidonic acid to yield PGH2 by PGH2 synthase (or, prostaglandin endoperoxide synthase). This enzyme is an ER membrane-bound protein that has two catalytic activities: fatty acid cyclooxygenase (COX), which requires two molecules of O2, and peroxidase, which requires reduced glutathione (see p. 148). PGH2 is converted to a variety of PG and TX, as shown in Figure 17.23, by cell-specific synthases. [Note: PG contain a five-carbon ring, whereas TX contain a heterocyclic six-membered oxane ring (see Fig. 17.21).] Two isozymes of PGH2 synthase, usually denoted as COX-1 and COX-2, are known. COX-1 is made constitutively in most tissues and is required for maintenance of healthy gastric tissue, renal homeostasis, and platelet aggregation. COX-2 is inducible in a limited number of tissues in response to products of activated immune and inflammatory cells. [Note: The increase in PG synthesis subsequent to the induction of COX-2 mediates the pain, heat, redness, and swelling of inflammation and the fever of infection.] 2.