Alcohol Dehydrogenase
Alcohol dehydrogenase (ADH) is located in the cytosol of stomach and liver cells and functions as the main enzyme for alcohol metabolism (5). ADH has a low Km and becomes saturated, reaching its Vmax, even at low concentrations of ethanol. Therefore, the enzyme appears to show zero-order kinetics because once the enzyme is saturated, the reaction rate is no longer dictated by the concentration of the ethanol (3).
Figure 5: Mechanism of alcohol dehydrogenase. Note that the Zinc atom is coordinated in the active site by Cys-174, Cys-46 and His-67, however, these residues were left out of the mechanism to emphasize the active residues.
ADH is an oxidoreductase enzyme that oxidizes alcohol to acetaldehyde while subsequently reducing an NAD+ cofactor to NADH. A Zn2+ atom is coordinated in the active site by Cys-174, Cys-46 and His-67 and functions to position the alcohol group of ethanol in the active site. Ser-48 and His-51 function similarly to a catalytic dyad, acting as a charge-relay network to help deprotonate the ethanol and activate it to be oxidized to the aldehyde. Before ethanol enters, a water molecule is initially positioned in the active site, but dissociates when the ethanol enters. At the end of the mechanism, water again enters the active site when the oxidized substrate—acetaldehyde—leaves (6).
Figure 6: The active site of ADH-1. The zinc atom (purple) coordinates with an ethanol molecule as described above, with His-51 and Ser-48 shown in blue and Cys-174, Cys-46, and His-67 shown in red (4).
Figure 7: Another view of the active site of ADH-1, depicting a side view of ethanol (red/green/white) coordinating with the zinc molecule (purple) (4).
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