Inhibition by GTN of ALDH2-catalyzed hydrolysis of
p-nitrophenylacetate. The figure shows the formation of
p-nitrophenol from p-NPA, as monitored at 400 nm. Panel
A shows that, in the absence of NAD+, GTN did not
significantly affect esterase activity. However, inactivation set in
immediately after the addition of NAD+. Experimental conditions
were: p-NPA (0.2 mm) in 50 mm potassium
Pi (pH 7.4) was present at the start of the reaction; ALDH2 (33
μg/ml), GTN (0.1 mm), DTT (0.2 mm), and
NAD+ (0.2 mm) were added as indicated. Curve fitting as
described in the legend to Fig.
1 yielded (1.0 ± 0.5) × 10-5 absorbance
units (a.u.)/s for the uncatalyzed reaction, (1.07 ± 0.02)
× 10-3 a.u./s for the initial rate, (1.083 ± 0.008)
× 10-3 a.u./s and (1.15 ± 0.01) ×
10-3 a.u./s after addition of GTN and DDT, respectively, (1.051
± 0.008) × 10-2 s-1 for the apparent
inactivation rate constant after addition of NAD+, and (7.2
± 0.1) × 10-5 a.u./s for the residual activity.
Panel B demonstrates that GTN inactivates the enzyme in the presence
of NAD+. Experimental conditions: p-NPA (0.2
mm) and NAD+ (0.2 mm) in 50 mm
potassium Pi (pH 7.4) were present at the start of the reaction;
ALDH2 (33 μg/ml) and GTN (0.1 mm) were added as indicated. Curve
fitting yielded the following results: (0.048 ± 0.009) ×
10-3 a.u./s for the uncatalyzed reaction, (3.65 ± 0.08)
× 10-3 a.u./s for the initial activity, (2.6 ± 0.1)
× 10-2 s-1 for the apparent inactivation rate
constant, and (0.0567 ± 0.0008) × 10-3 a.u./s for the
residual activity.