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ago in Medicinal Chemistry by (270 points)
How does the drug aspirin specifically interact with the enzymes involved in the production of prostaglandins to reduce inflammation and pain in the body?

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ago by (530 points)
Aspirin, also known as acetylsalicylic acid, is a nonsteroidal anti-inflammatory drug  NSAID  that is commonly used to reduce inflammation, pain, and fever. Its mechanism of action involves the inhibition of enzymes involved in the production of prostaglandins, which are hormone-like substances that play a crucial role in mediating inflammation, pain, and fever in the body.The key enzyme involved in the production of prostaglandins is called cyclooxygenase  COX . There are two main isoforms of this enzyme: COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and is responsible for maintaining normal physiological functions, such as protecting the stomach lining and regulating blood flow. COX-2, on the other hand, is induced during inflammation and is responsible for the production of prostaglandins that mediate pain, inflammation, and fever.Aspirin exerts its anti-inflammatory and analgesic effects by irreversibly inhibiting both COX-1 and COX-2 enzymes. It does this by acetylating a serine residue  Ser-530 in COX-1 and Ser-516 in COX-2  in the active site of the enzyme. This acetylation blocks the access of arachidonic acid, a substrate for prostaglandin synthesis, to the active site of the enzyme, thereby preventing the conversion of arachidonic acid to prostaglandin H2  PGH2 . PGH2 is a precursor for the synthesis of various prostaglandins  such as PGE2, PGD2, PGF2  and thromboxanes  such as TXA2 , which are responsible for mediating inflammation, pain, and fever.By inhibiting the COX enzymes and subsequently reducing the production of prostaglandins and thromboxanes, aspirin effectively alleviates inflammation, pain, and fever in the body. It is important to note that aspirin's inhibition of COX-1 can also lead to some side effects, such as gastrointestinal irritation and increased bleeding risk, due to the disruption of the protective and blood flow-regulating functions of COX-1-derived prostaglandins.
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