An antimetabolite is a substance that interferes with a normal metabolic pathway, usually because it has a similar shape to one of the pathway's substrates. Antimetabolite antibiotics block pathways that bacteria need but human cells do not use.The best-known example is the sulfonamides (sulfa drugs). Bacteria must make their own folic acid (folate), which they need to make nucleotides for DNA and RNA. An early step in the pathway uses the enzyme dihydropteroate synthase, whose substrate is para-aminobenzoic acid (PABA).Sulfonamide molecules are similar in shape to PABA. They fit into the active site of the enzyme and act as competitive inhibitors: while a sulfonamide occupies the active site, PABA cannot bind. So less folic acid is made, and the bacteria cannot make enough nucleotides to replicate their DNA and divide.PABA → (dihydropteroate synthase) → further steps → folic acid Because the inhibition stops growth rather than killing the cells, sulfonamides are bacteriostatic. As with any competitive inhibitor, a high concentration of PABA reduces their effect.Selective toxicity. Human cells do not make folic acid; we take it in from our diet. We do not have the enzyme that sulfonamides inhibit, so our cells are unaffected.
Trimethoprim is another antimetabolite. It inhibits a later enzyme in the same pathway, dihydrofolate reductase. The bacterial form of this enzyme is much more sensitive to trimethoprim than the human form. Trimethoprim is often combined with a sulfonamide, blocking two steps in the pathway at once.
Trimethoprim is another antimetabolite. It inhibits a later enzyme in the same pathway, dihydrofolate reductase. The bacterial form of this enzyme is much more sensitive to trimethoprim than the human form. Trimethoprim is often combined with a sulfonamide, blocking two steps in the pathway at once.