Substrate analog

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Substrate analogs (substrate state analogues), are chemical compounds with a chemical structure that resemble the substrate molecule in an enzyme-catalyzed chemical reaction. Substrate analogs can act as competitive inhibitors of an enzymatic reaction. An example is phosphoramidate to the Tetrahymena group I ribozyme. [1] Other examples of substrate analogs include 5’-adenylyl-imidodiphosphate, a substrate analog of ATP, and 3-acetylpyridine adenine dinucleotide, a substrate analog of NADH. [2]

As a competitive inhibitor, substrate analogs occupy the same binding site as its analog, and decrease the intended substrate’s efficiency. [3] The maximum rate (Vmax) remains the same [4] while the intended substrate’s affinity (measured by the Michaelis constant KM) is decreased. [5] This means that less of the intended substrate will bind to the enzyme, resulting in less product being formed. In addition, the substrate analog may also be missing chemical components that allow the enzyme to go through with its reaction. This also causes the amount of product created to decrease.

Substrate analogs usually bind to the binding site reversibly. This means that the binding of the substrate analog to the enzyme’s binding site is non-permanent. The effect of the substrate analog can be nullified by increasing the concentration of the originally intended substrate. [6] There are also substrate analogs that bind to the binding site of an enzyme irreversibly. If this is the case, the substrate analog is called an inhibitory substrate analog, a suicide substrate, or a Trojan horse substrate. [7] An example of a substrate analog that is also a suicide substrate/Trojan horse substrate is penicillin, which is an inhibitory substrate analog of peptidoglycan. [8]

Some substrate analogs can still allow the enzyme to synthesize a product despite the enzyme’s inability to metabolize the substrate analog. These substrate analogs are known as gratuitous inducers. [9] An example of a substrate analog that is also a gratuitous inducer is IPTG (isopropyl β-D-1-thiogalactopyranoside), a substrate analog and gratuitous inducer of β-galactosidase activity. [10]

See also

Related Research Articles

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Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in this way can reveal the catalytic mechanism of this enzyme, its role in metabolism, how its activity is controlled, and how a drug or a modifier might affect the rate.

<span class="mw-page-title-main">Enzyme inhibitor</span> Molecule that blocks enzyme activity

An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction.

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Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected by this principle, but several classes of competitive inhibition are especially important in biochemistry and medicine, including the competitive form of enzyme inhibition, the competitive form of receptor antagonism, the competitive form of antimetabolite activity, and the competitive form of poisoning.

References

  1. ↑ Hanna, Raven L.; Gryaznov, Sergei M.; Doudna, Jennifer A. (2000-11-01). "A phosphoramidate substrate analog is a competitive inhibitor of the Tetrahymena group I ribozyme". Chemistry & Biology. 7 (11): 845–854. doi: 10.1016/S1074-5521(00)00033-8 . ISSN   1074-5521. PMID   11094338.
  2. ↑ Stein, Ross L. Kinetics of Enzyme Action: Essential Principles for Drug Hunters. Hoboken, NJ: John Wiley, 2011. Print. p185. ISBN   9780470414118
  3. ↑ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN   9781133106296
  4. ↑ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN   9781133106296
  5. ↑ Cannon, Joseph G. Pharmacology for Chemists. Oxford: Oxford UP, 2007. Print. p70. ISBN   9780841239272
  6. ↑ Cannon, Joseph G. Pharmacology for Chemists. Oxford: Oxford UP, 2007. Print. p70. ISBN   9780841239272
  7. ↑ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN   9781133106296
  8. ↑ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN   9781133106296
  9. ↑ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN   9781133106296
  10. ↑ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN   9781133106296
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