Differences in the Interactions of Liver Alcohol Dehydrogenases with Probes Binding into the Substrate Pocket

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Abstract
The interactions of 3 groups of probes (berberine alkaloids, tricyclic psychopharmaca and acridine derivatives) with isoenzymes of horse liver alcohol dehydrogenase and with rat liver alcohol dehydrogenase were examined. These compounds inhibit the activity of the EE isoenzyme of horse liver alcohol dehydrogenase but differ in their behavior towards the steroid-active enzymes (i.e., the ES isoenzyme of horse liver alcohol dehydrogenase and alcohol dehydrogenase from rat liver): psychopharmaca inhibit, acridines activate and berberines do not bind. The ligands differ also in their influence on the modificiation of the EE isoenzyme by iodoacetate. Polarities (expressed as Kosower''s Z values) of the respective binding sites on the EE isoenzyme were estimated from optical properties of bound probes. Berberines bind into a very hydrophobic area of the enzyme molecule, the binding site for psychopharmaca ceaticus is moderately hydrophobic and that for acridines is rather polar. Steric arrangements of the binding sites are also discussed. Distinct binding sites (3) exist for these ligands in the substrate pocket of liver alcohol dehydrogenase.