Caracteres de l'inhibition de la glutamate, de l'isocitrate et de l'alcool deshydrogenases par les analogues formique, acetique et proprionique de la triiodo-3,5,3'- l-thyronine

Abstract

3,5,3'-Triiodo-thyroformic (TF 3), 3,5,3'-triiodo-thyroacetic (TA 3) and 3,5,3'-triiodo-thyropropionic (TP 3) acids, which are structural analogs of 3,5,3'-triiodo-L-thyronine (LT 3), have been found to inhibit beef liver glutamate dehydrogenase (GlDH), horse liver alcohol dehydrogenase (ADH) and pig heart isocitrate dehydrogenase (ICDH), but different mechanisms are involved. TF 3, TA 3 and TP 3 inhibit GlDH non competitively with respect to NADP, but competitively with ADP-ribose, an activator of GlDH. For the inhibition of ADH, the three iodinated derivatives compete with NAD and ADP-ribose; ADP-ribose being itself competitive with NAD. So, it appears that TF 3, TA 3 and TP 3 interfere with the coenzyme binding by blocking the binding site of the ADP-ribose portion of the coenzyme. These iodinated inhibitors quench the enhanced fluorescence which originates from the enzyme-coenzyme binding. However, in the case of the GlDH, TP 3 exhibit an opposite effect. E.s.r. studies showed that ICDH inhibition by TA 3, did not result from the chelation of Mn 2+, but that TA 3 impaired binding of Mn 2+ to the enzyme and coenzyme.