Enzyme inhibitors are molecules that decrease the activity of enzymes, and knowledge about inhibitors can, for example, be used in developing drugs or in the study of biochemical pathways, because inhibitors provide a way to interfere with these pathways. Enzyme inhibitors can be either irreversible or reversible; irreversible inhibitors decrease enzymatic activity by destroying the enzyme through various mechanisms, while reversible inhibitors keep the enzyme functional. The inhibitors we will study here are reversible inhibitors
Types of inhibition
The mechanisms of enzyme inhibitors can be classified into 3 major groups: Competitive inhibitors, uncompetitive inhibitors, and mixed inhibitors. Competitive inhibitors work by binding to the active site of the enzyme in competition with the substrate; uncompetitive inhibitors bind to the enzyme-substrate complex at a site distinct from the active site, but they cannot bind to the enzyme alone, and mixed inhibitors can bind to both the enzyme and the enzyme-substrate complex at a site distinct from the active site
The mechanisms of enzyme inhibition can be thought of as an extension to the Michaelis-Menten mechanism and competitive and un-competitive inhibition can be regarded as a special case of mixed inhibition (see Figure 1a), where
Just like the Michealis-Menten equation, this equation can be rearranged to fit a double-reciprocal plot:
Figure 1: The overall enzymatic reaction and the extension of the enzyme inhibition mechanism.
The enzyme alcohol dehydrogenase is not completely specific for ethanol; it also catalyzes the formation of aldehydes from other alcohols. One of these alcohols is methanol, which is metabolized into formaldehyde and other toxic compounds that can cause blindness or death. Methanol poisoning is quite common, and can be caused by the ingestion of homemade alcohol. Methanol and ethanol are thus competitive substrates, and ethanol is actually used to prevent poising after the ingestion of methanol, because it inhibits ADH in catalyzing the oxidation of this compound.
Calculation of kinetic parameters
See the following pages for details of how to calculate the kinetic parameters for different inhibitors:
Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2008). Principles of Biochemistry (5th ed.). New York, NY: W.H. Freeman and Company. ISBN 978-0-7167-7108-1.
Atkins, Peter W.; de Paula, Julio; Friedman, Ronald (2009). Quanta, Matter, and Change: A molecular approach to physical chemistry. Oxford University Press. ISBN 978-0-19-920606-3.
Beatty, L., Green, R., Magee, K. and Zed, P. (2013) A Systematic Review of Ethanol and Fomepizole Use in Toxic Alcohol Ingestions. Emerg. Med. Int. 2013, 638057.