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13.2E: Inhibiting Essential Metabolite Synthesis

  • Page ID
    8710
    • Contributed by Boundless
    • General Microbiology at Boundless

    An antimetabolite is a chemical that inhibits the use of a metabolite, a chemical that is part of normal metabolism.

    Learning Objectives

    • Distinguish between the three main types of antimetabolite antibiotics (antifolates, pyrimidine and purine analogues)

    Key Points

    • The presence of antimetabolites can have toxic effects on cells, such as halting cell growth or cell division.
    • Antimetabolites are also used as antibiotics.
    • The three main types of antimetabolite antibiotics are antifolates, pyrimidine analogues and purine analogues.

    Key Terms

    • antimetabolite: Any substance that competes with or inhibits the normal metabolic process, often by acting as an analogue of an essential metabolite

    An antimetabolite is a chemical that inhibits the use of a metabolite, a chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as antifolates that interfere with the use of folic acid. The presence of antimetabolites can have toxic effects on cells, such as halting cell growth or cell division.

    Antimetabolites are also used as antibiotics. There are three main types of antimetabolite antibiotics. The first, antifolates impair the function of folic acid leading to disruption in the production of DNA and RNA. For example, methotrexate is a folic acid analogue, and owing to structural similarity with folic acid, methotrexate binds and inhibits the enzyme dihydrofolate reductase, and thus prevents the formation of tetrahydrofolate. Because tetrahydrofolate is essential for purine and pyrimidine synthesis, its deficiency can lead to inhibited production of DNA, RNA and proteins.

    image
    Figure: Folic Acid Structure: This is the chemical structure of folic acid.

    The second type of antimetabolite antibiotics consist of pyrimidine analogues which mimic the structure of metabolic pyrimidines. Three nucleobases found in nucleic acids, cytosine (C), thymine (T), and uracil (U), are pyrimidine derivatives and the pyrimidine analogues disrupt their formation and consequently disrupt DNA and RNA synthesis.

    image
    Figure: Pyrimidine Structure: This is the chemical structure of pyrimidine.

    The purine analogues are the third type of antimetabolite antibiotics and they mimic the structure of metabolic purines. Two of the four bases in nucleic acids, adenine and guanine, are purines. Purine analogues disrupt nucleic acid production. For example, azathioprine is the main immunosuppressive cytotoxic substance that is widely used in transplants to control rejection reactions by inhibiting DNA synthesis in lymphocytes.

    image
    Figure: Purine Structure: This is the chemical structure of purine.

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