Inhibition of dehydrogenase enzymes by hexachlorophene

Abstract

Low concentrations of the antibacterial agent hexachlorophene (HCP) inhibited a number of pyridine nucleotide-linked dehydrogenase enzymes, including bovine liver glutamate dehydrogenase (GDH), beef heart malate dehydrogenase (MDH), torula yeast glucose 6-phosphate dehydrogenase (G-6-P-D), horse liver alcohol dehydrogenase (ADH), pig heart isocitrate dehydrogenase (ICD), and beef heart lactate dehydrogenase (LDH). Initial velocity studies at appropriate enzyme concentrations gave I 50 values for the dehydrogenases which ranged between 1.6 μM for GDH and 105 μM for ICD and LDH. More detailed kinetic analyses of G-6-P-D, ICD and GDH showed that inhibition by HCP in most cases was of the noncompetitive type. Calculations made from the kinetic data gave apparent K i values with G-6-P-D, of 59 μM for NADP + and of 38 μM for glucose 6-phosphate; with ICD, of 1.0 μM for NADP + and of 25 μM for isocitrate; and, with GDH, of 2.0 μM for NADH, of 7.4 μM for α-ketoglutarate, and of 2.3 μM for ammonium acetate.