Question

Prostaglandin synthase, a bifunctional enzyme, A. catalyzes the rate-limiting step of prostaglandin synthesis. B. is inhibited by anti-inflammatory steroids. C. contains both a cyclooxygenase and a peroxidase component. D. produces \(\mathrm{PGG}_{2}\) as the end product. E. uses as substrate the pool of free arachidonic acid in the cell.

Short answer

Short Answer: The true statements about prostaglandin synthase are A) it catalyzes the rate-limiting step of prostaglandin synthesis, B) anti-inflammatory steroids inhibit the enzyme, C) it has two components, cyclooxygenase and peroxidase, and E) its substrate is free arachidonic acid. Statement D is false because the end product of prostaglandin synthase is prostaglandin H2 (PGH2), not prostaglandin G2 (PGG2).

Step-by-step solution

Prostaglandin synthase's role in prostaglandin synthesis

Prostaglandin synthase does catalyze the rate-limiting step of prostaglandin synthesis, which means converting arachidonic acid into prostaglandin H2 (PGH2). So, statement A is true.

Effect of anti-inflammatory steroids on prostaglandin synthase

Anti-inflammatory steroids inhibit prostaglandin synthase by binding to its active site and preventing the enzyme from converting arachidonic acid into prostaglandins, which are involved in inflammation. Therefore, statement B is true.

Components of prostaglandin synthase

Prostaglandin synthase consists of two components: cyclooxygenase (COX) and peroxidase. Cyclooxygenase is responsible for converting arachidonic acid into prostaglandin G2 (PGG2), while peroxidase converts PGG2 into prostaglandin H2 (PGH2). This means that statement C is true as well.

End product of prostaglandin synthase

As mentioned earlier, prostaglandin synthase converts arachidonic acid into prostaglandin H2 (PGH2), not into prostaglandin G2 (PGG2). Therefore, statement D is false.

Substrate of prostaglandin synthase

The substrate for prostaglandin synthase is the free arachidonic acid in the cell, which the enzyme then converts into prostaglandin H2 (PGH2). Considering this, statement E is true.

Conclusion

After analyzing the given statements, we can conclude that A, B, C, and E are true statements related to prostaglandin synthase, while statement D is false, as the end product of the enzyme is prostaglandin H2 (PGH2) not prostaglandin G2 (PGG2).

Key concepts

Prostaglandin Synthesis

Prostaglandin synthesis is a vital physiological process, involving the conversion of arachidonic acid to a series of prostaglandins, which play roles in various body functions such as inflammation, pain, fever regulation, and the protection of the gastric mucosa. The key enzyme in this process is prostaglandin synthase, which has two main activities: cyclooxygenase and peroxidase. It kicks off the process by producing prostaglandin G2 (PGG2) from arachidonic acid and then swiftly turns PGG2 into prostaglandin H2 (PGH2), the precursor for other prostaglandins and thromboxanes. This pathway is intricately regulated, and disruptions can lead to several inflammatory conditions, which is why it's often targeted by various drugs to manage pain and inflammation.

Understanding this cascade is crucial for students, as it illuminates the balance between different physiological states and how medications can alter these states for therapeutic outcomes.

Anti-inflammatory Steroids

Anti-inflammatory steroids, commonly known as corticosteroids, are synthetic drugs that mimic the action of the hormone cortisol produced by the adrenal glands. They exert a profound influence on various bodily functions, including the immune response. One of their pivotal actions is the inhibition of prostaglandin synthesis. They achieve this by decreasing the release of arachidonic acid and by inhibiting phospholipase A2, an enzyme essential for releasing arachidonic acid from cell membrane lipids. This mechanism underpins their versatility in treating a plethora of inflammatory conditions ranging from asthma to rheumatoid arthritis.

Students should not confuse these steroids with anabolic steroids, which are known for their muscle-building effects.

Arachidonic Acid

Arachidonic acid is a polyunsaturated omega-6 fatty acid that serves as a central precursor in the synthesis of prostaglandins, leukotrienes, and other eicosanoids. It's stored in cell membranes, bound to phospholipids, and is released by the action of phospholipase A2. Once free, it can be metabolized by enzymes like prostaglandin synthase to produce various eicosanoids. These molecules are key players in the body's inflammatory responses and other important physiological processes such as platelet aggregation and the constriction or dilation of blood vessels.

Food Sources

• Meat
• Eggs
• Dairy products

Dietary balance between omega-6 (like arachidonic acid) and omega-3 fatty acids is important for maintaining health.

Cyclooxygenase (COX)

Cyclooxygenase, commonly abbreviated as COX, is an enzyme that has two isoforms, COX-1 and COX-2. COX-1 is involved in maintaining the normal physiological function of various tissues, while COX-2 is inducible and usually expressed during pathological conditions like inflammation. The COX enzyme is responsible for the first step in prostaglandin synthesis — converting arachidonic acid into prostaglandin G2 (PGG2). This role makes COX a critical target for nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, which act by inhibiting the activity of COX and thus reduce the production of pro-inflammatory prostaglandins. It's important for students to recognize the differences between the two COX isoforms since selective COX-2 inhibitors were developed to minimize the gastrointestinal side effects common with traditional NSAIDs that inhibit both COX-1 and COX-2.

Peroxidase

The peroxidase component of prostaglandin synthase often receives less attention than the cyclooxygenase component, but it is equally important. Once PGG2 is formed by COX, peroxidase is the enzyme that converts it into prostaglandin H2 (PGH2), the immediate precursor to various other prostaglandins and thromboxanes. These metabolic steps are part of the same bifunctional enzyme complex, and understanding this dual function illustrates the tightly regulated nature of eicosanoid production.

This knowledge is foundational for biomedical studies as it allows students to appreciate the therapeutic targeting of this enzyme in the development of anti-inflammatory and antithrombotic drugs.