Delving into the intricate world of prostaglandin synthesis, this review offers a comprehensive examination of prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2), also known as cyclooxygenases-1 and 2 (COX-1 and COX-2). As major targets of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, and COX-2 inhibitors, these enzymes are central to understanding inflammation, pain, and fever reduction. The article is about their structural, cellular, and molecular biology. The review meticulously examines the mechanistic relationship between the enzyme structures and cyclooxygenase and peroxidase catalysis. It highlights how structural differences in PGHS-2 confer differential sensitivity to COX-2 inhibitors, which is crucial for the development of selective and effective drugs. The authors further explore evidence for independent signaling by PGHS-1 and PGHS-2, illuminating the intricate mechanisms that regulate PGHS-2 gene expression. In conclusion, this review synthesizes the complex interplay between the structure, function, and regulation of cyclooxygenases, providing a valuable resource for researchers in biochemistry, pharmacology, and related fields. Understanding these enzymes is critical for developing targeted therapies to reduce inflammation, pain, and the risk of associated diseases.
Published in Annual Review of Biochemistry, this paper is highly relevant to the journal's focus on providing comprehensive and authoritative reviews of key topics in biochemistry. By examining the structure, function, and regulation of cyclooxygenases, the review aligns with the journal's commitment to advancing knowledge in fundamental biochemical processes.