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.

• Control of Metabolism Through Enzyme Regulation

  • In competitive inhibition, an inhibitor molecule is similar enough to a substrate that it can bind to the enzyme's active site to stop it from binding to the substrate.
  • The substrate can still bind to the enzyme, but the inhibitor changes the shape of the enzyme so it is no longer in optimal position to catalyze the reaction.
  • The binding of this allosteric inhibitor changes the conformation of the enzyme and its active site, so the substrate is not able to bind.
  • Competitive inhibitors affect the initial rate, but do not affect the maximal rate, whereas noncompetitive inhibitors affect the maximal rate.
  • Allosteric inhibitors modify the active site of the enzyme so that substrate binding is reduced or prevented.

• 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.

• Secondary & Tertiary Structure of Large Peptides and Proteins

  • Similarly, hemoglobin has a competitive binding affinity for cyanide, sulfur monoxide, nitrogen dioxide and sulfides including hydrogen sulfide .
  • Such drugs function as inhibitors, binding to the active site by mimicking the tetrahedral intermediate of its substrate, thus disabling the enzyme.

• Four-Membered Rings

  • Example 4 demonstrates that this approach to azetidine formation works well in the absence of competition.
  • The relatively rigid configuration of the substrate in example 3, favors oxetane formation and prevents an oxirane cyclization from occurring.

• Diuretics

  • Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted tubule.
  • The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations: Aldosterone antagonists: spironolactone, which is a competitive antagonist of aldosterone.

• Teratogens

  • Smoking may exert its effects through competitive binding of carbon monoxide with hemoglobin and/or through the various other components found in cigarettes that cause adverse biological effects.
  • Angiotensin Converting Enzyme (ACE) inhibitors will cause fetal renal failure and oligohydramnios which lead to pulmonary hypoplasia and limb contracture.