Para-aminosalicylic acid (PAS), a second-line anti-TB drug, inhibits folate synthesis by which mechanism?

• A Competitive inhibition of dihydropteroate synthase (DHPS) ✓
• B Competitive inhibition of dihydrofolate reductase (DHFR)
• C Sequestration of p-aminobenzoic acid (PABA), starving the folate pathway
• D Inhibition of thymidylate synthase, blocking thymidine synthesis

Explanation

PAS is a structural analogue of para-aminobenzoic acid (PABA) and acts as a false substrate that competes with PABA for dihydropteroate synthase (DHPS), blocking the condensation step of folate synthesis. PAS is incorporated into a non-functional dihydrofolate analogue (hydroxy-PAS), starving thymidylate synthesis. This mechanism is analogous to sulfonamides. PAS is now rarely used due to GI intolerance.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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