Editing Alcohol dehydrogenase (section)

== Mechanism of action in humans ==

=== Steps ===
# Binding of the coenzyme NAD<sup>+</sup>
# Binding of the alcohol substrate by coordination to zinc(II) ion
# Deprotonation of His-51
# Deprotonation of [[Nicotinamide riboside|nicotinamide ribose]]
# Deprotonation of Thr-48
# Deprotonation of the alcohol
# Hydride transfer from the [[alkoxide]] ion to NAD<sup>+</sup>, leading to NADH and a zinc-bound aldehyde or ketone
# Release of aldehyde.

The mechanism in yeast and bacteria is the reverse of this reaction. These steps are supported through kinetic studies.<ref name="Hammes">{{cite journal | vauthors = Hammes-Schiffer S, Benkovic SJ | title = Relating protein motion to catalysis | journal = Annual Review of Biochemistry | volume = 75 | pages = 519–41 | year = 2006 | pmid = 16756501 | doi = 10.1146/annurev.biochem.75.103004.142800 }}</ref>

=== Involved subunits ===
The substrate is coordinated to the zinc and this enzyme has two zinc atoms per subunit. One is the active site, which is involved in catalysis. In the active site, the ligands are Cys-46, Cys-174, His-67, and one water molecule. The other subunit is involved with structure. In this mechanism, the hydride from the alcohol goes to NAD<sup>+</sup>. Crystal structures indicate that the His-51 deprotonates the nicotinamide ribose, which deprotonates Ser-48. Finally, Ser-48 deprotonates the alcohol, making it an aldehyde.<ref name="Hammes" /> From a mechanistic perspective, if the enzyme adds hydride to the [[re face]] of NAD<sup>+</sup>, the resulting hydrogen is incorporated into the pro-R position. Enzymes that add hydride to the re face are deemed Class A dehydrogenases.{{cn|date=June 2024}}