competitive substrate inhibitors

Examples of competitive substrate inhibitors in the following topics:

• Nucleotide and Nonnucleotide Reverse Transcriptase Inhibitors

  • The first two inhibitors act on the same principle.
  • Nucleoside and nucleotide inhibitors are also called competitive substrate inhibitors.
  • Non-nucleotide inhibitors are non-competitive inhibitorsof reverse transcriptase.
  • Resistance to the non-nucleotide inhibitors is caused by mutations in the inhibitor binding site of the enzyme.
  • Such mutations prevent the binding of the inhibitor to the enzyme.

• Protease Inhibitors

  • Natural protease inhibitors are found in Shiitake mushrooms.
  • Protease inhibitors are short peptide-like molecules that are competitive inhibitors of the enzyme.
  • Saquinavir is the first clinically used peptide-like inhibitor.
  • Some protease inhibitors do not mimic peptides in their structure.
  • It is one of the major drawbacks of protease inhibitors therapy.

• Enzymes Used in Industry

  • In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products .
  • However, enzymes do differ from most other catalysts in that they are highly specific for their substrates.
  • Inhibitors can decrease enzyme activity; activators can increase activity.
  • Many drugs and poisons are enzyme inhibitors.
  • Activity is also affected by temperature, pressure, chemical environment (e.g., pH), and substrate concentration.

• Benzoate Catabolism

  • Rhodococci typically metabolize aromatic substrates by first oxygenating the aromatic ring to form a diol (two alcohol groups).
  • Then, the ring is cleaved with intra/extradiol mechanisms, opening the ring and exposing the substrate to further metabolism.
  • An example of this is the use of Rhodococcus to produce indene, a precursor to the AIDS drug CrixivanTM, a protease inhibitor, and containing two of the five chiral centers needed in the complex.

• Synthetic Antimicrobial Drugs

  • In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis.
  • The sulfonamide chemical moiety is also present in other medications that are not antimicrobials, including thiazide diuretics (including hydrochlorothiazide, metolazone, and indapamide, among others), loop diuretics (including furosemide, bumetanide, and torsemide), sulfonylureas (including glipizide, glyburide, among others), and some COX-2 inhibitors (e.g., celecoxib), and acetazolamide.