Table 1.

Kinetic Constants for the Inactivation of hOAT and Reversible Inhibition of GABA-AT by 4–6^a

Cmpd	Structure	hOAT					GABA-AT
		kinact (min−1)	KI (mM)	kinact /KI (min−1mM−1)	Partition ratioc	Fluorideion release (eq.)d	Ki (mM)
1		0.09 ± 0.01	0.09 ± 0.03	1.0 ± 0.4	12 ± 1b	79 ± 2b	5.2 ± 0.6
4		0.01 ± 0.00	4.00 ± 1.00	0.003 ± 0.001	2200 ± 70	3400 ± 30	0.1 ± 0.0
5		0.03 ± 0.01	2.00 ± 0.90	0.015 ± 0.006	790 ± 35	750 ± 60	1.4 ± 0.1
6		0.08 ± 0.01	0.06 ± 0.03	1.3 ± 0.7	34 ± 0	34 ± 1	1.1 ± 0.1

^ak_inact and K_I values were determined by the equation: k_obs = k_inact×[I]/(K_I + [I]) and presented as means and standard errors. K_i values were calculated by the Cheng-Prusoff equation: K_i = IC₅₀/(1+[S]/K_m) and shown as means and standard errors. IC₅₀ values were obtained using nonlinear regression analysis in GraphPad Prism 8 of a 9-point enzymatic assay with a 2-fold serial dilution against GABA-AT. The partition ratios were determined under conditions in the presence of α-KG, while fluoride ion release results were determined in the absence of α-KG.

^bData were extracted from Reference ¹².

^cEnzyme activity remaining was measured as a function of the number of equivalents of 4–6 relative to enzyme concentration. Linear regression analysis was used on the linear portion of the curves to obtain the x-intercept, which was the turnover number (partition ratio = turnover number −1). Data are shown as the means with standard errors.

^dThe fluoride ion release experiments were performed in triplicates. Data are presented as the means with standard deviations.