Substrate analog

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]

As a competitive inhibitor, substrate analogs occupy the same binding site as its analog, and decrease the intended substrate’s efficiency.[2] The Vmax remains the same[3] while the intended substrate’s affinity is decreased.[4] 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 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.[5]

Other examples of substrate analogs include: 5’-adenylyl-imidodiphosphate: substrate analog of ATP 3-acetylpyridine adenine dinucleotide: substrate analog of NADH [6]

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.[7]

Example of a substrate analog that is also a gratuitous inducer: IPTG (isopropyl β-thiogalactoside: substrate analog and gratuitous inducer of β-galactosidase activity [8]

There are even 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 even a Trojan horse substrate.[9]

Example of a substrate analog that is also a suicide substrate/Trojan horse substrate: Penicillin: substrate analog and suicide substrate/Trojan horse substrate of peptidoglycan [10]

See alsoEdit

ReferencesEdit

  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. ^ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN 9781133106296
  3. ^ Garrett, Reginald H.; Grisham, Charles M. (2013). Biochemistry (5th ed. ed.). Belmont, CA: Brooks/Cole, Cengage Learning. p. 108. ISBN 9781133106296
  4. ^ Cannon, Joseph G. Pharmacology for Chemists. Oxford: Oxford UP, 2007. Print. p70. ISBN 9780841239272
  5. ^ Cannon, Joseph G. Pharmacology for Chemists. Oxford: Oxford UP, 2007. Print. p70. ISBN 9780841239272
  6. ^ Stein, Ross L. Kinetics of Enzyme Action: Essential Principles for Drug Hunters. Hoboken, NJ: John Wiley, 2011. Print. p185. ISBN 9780470414118
  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