SELECTIVE INHIBITION OF THE SPERM-SPECIFIC LACTATE DEHYDROGENASE ISOZYME-C4 BY N-ISOPROPYL OXAMATE
1997
Abstract In the present study, we demonstrated that the attachment of the nonpolar isopropylic carbon chain in the nitrogen of oxamate, converted this competitive inhibitor of LDH isozymes into a powerful selective inhibitor of mouse LDH-C4. The comparative study of the inhibitory effect of oxamate and N -isopropyl oxamate on mouse LDH isozymes pointed out that the isopropylic carbon chain conferred upon N -isopropyl oxamate a high affinity for LDH-C4 and a marked decrease in the affinity for the other isozymes since oxamate showed more inhibitory effect on LDH-1 ( K i =0.06 mM) and LDH-5 ( K i =0.08 mM), and less inhibitory effect on LDH-C4 ( K i =0.25 mM). On the other hand, N -isopropyl oxamate showed the highest inhibitory effect on LDH-C4 ( K i =0.014 mM) and poor inhibitory effect on LDH-1 ( K i =0.4 mM) and LDH-5 ( K i =0.8 mM). Apparently, the enzymatic inactivation proceeded through a reversible binding of N -isopropyl oxamate, facilitated by nonpolar interactions with a hydrophobic region present only in the active site of mouse LDH-C4, resulting in a selective inhibition of this isozyme in comparison with the other LDH isozymes. N -isopropyl oxamate was also a powerful competitive inhibitor of LDH-C4 ( K i =0.015 mM) compared with oxamate ( K i =0.35 mM), using α-ketoisocaproate as a substrate.
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