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Pathway Description
Pyrazinamide Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2025-08-20
Last Updated: 2025-11-09
The pyrazinamide (PZA) pathway plays a crucial role in the treatment of Mycobacterium tuberculosis infection. Pyrazinamide is a prodrug that requires activation by the bacterial enzyme pyrazinamidase/nicotinamidase (PncA). This enzyme converts PZA into its active form, pyrazinoic acid (POA), which accumulates inside the bacterium. In the acidic environment of infected tissues and within macrophages, POA interferes with several vital processes, including membrane energetics, fatty acid synthesis, and trans-translation, ultimately leading to bacterial death. Mutations in the pncA gene are the primary cause of PZA resistance, as they prevent activation of the drug. Because PZA is uniquely effective against dormant and slowly replicating bacteria in acidic environments, it is an essential component of first-line tuberculosis therapy, helping shorten treatment duration and improve cure rates.
References
Pyrazinamide Pathway References
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Pubmed: 14702039
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