Inhibition of carbonyl reductase activity in pig heart by alkyl phenyl ketones

Figures & data

Figure 1 Reduction of 4-BP to S( − )-PPOL catalyzed by PHCR.

Figure 2 Chemical structures of alkyl phenyl ketones used in this study.

Figure 3 Inhibitory effects of alkyl phenyl ketones on carbonyl reductase activity in pig heart cytosol. 4-BP at a concentration of 500 μM was used as the substrate. The concentration of alkyl phenyl ketones added as inhibitor was 500 μM. Each bar represents the mean ± S.D. of three to six experiments.

Table I.  Kinetic parameters for the reduction of alkyl phenyl ketones in pig heart cytosol.

Ketones	Km (mM)	Vmax/Km (munit/mg/mM)
Propiophenone	0.249 ± 0.046	28 ± 5
Butyrophenone	0.084 ± 0.014	109 ± 25
Valerophenone	0.048 ± 0.009	270 ± 47
Hexanophenone	0.037 ± 0.011	410 ± 13
Heptanophenone	0.078 ± 0.013	244 ± 13

The values are the mean ± S.D. of three or four experiments

Figure 4 Relationship between V_max/K_m values for the reduction of alkyl phenyl ketones and their inhibitory potencies for carbonyl reductase activity in pig heart cytosol. Plot: 1, propiophenone; 2, butyrophenone; 3, valerophenone; 4, hexanophenone; 5, heptanophenone.

Figure 5 Lineweaver-Burk plots for the reduction of 4-BP to S( − )-PPOL in the absence and in the presence of hexanophenone. ○, in the absence of hexanophenone; •, in the presence of hexanophenone (500 μM). Each point represents the mean ± S.D. of three or four experiments.

Figure 6 Proposed substrate-binding domain of PHCR.