The mechanism of inhibition of horse liver alcohol dehydrogenase by thyroxine and related compounds.

Thyroxine and related compounds have been found to be excellent inhibitors of horse liver alcohol dehydrogenase. The thyroid hormones appear to act by interfering with the normal coenzyme-binding mechanism. Triiodothyronine and thyroxine are uncompetitive inhibitors with regard to the coenzyme. In addition to inhibiting the enzyme activity, the thyroid hormone also quenches the enhanced fluorescence of the bound NADH and greatly reduces the magnitude of a Cotton effect in the optical rotatory dispersion spectrum which is attributed to bound coenzyme. Little effect on the over-all binding of the coenzymes was observed. However, the current findings are consistent with an inhibition scheme in which the thyroid hormones interfere with the binding of the nicotinamide portion of the coenzyme.