Stimulation of iodothyronine outer ring monodeiodinase by dihydrolipoamide.
The naturally occurring dithiol, dihydrolipoamide (DHL), has been found to be 6-10 times as potent as the synthetic dithiol, dithiothreitol, in stimulating iodothyronine outer ring monodeiodinase activity in the rat kidney. In the presence of NADH, the oxidized form is also active in stimulating the enzymatic activity in whole homogenates and in the postnuclear and mitochondrial, but not in the microsomal fraction. The covalently bound lipoamide in the mitochondrial alpha-keto acid dehydrogenase complexes, when reduced with substrates or NADH, was, however, ineffective. The activation of the enzyme by DHL was very similar to that obtained with dithiothreitol in respect to temperature dependence and inhibition by propylthiouracil and by dicoumarol, suggesting that these thiols activate the same enzyme through similar mechanisms. The higher potency of DHL cannot be explained on the basis of its greater lipophilicity or relatively proximal dithiol structure. The occurrence of DHL in mitochondria raises the possibility of a role as a thiol cofactor in enzymatic outer ring deiodination of T4 or rT3, although attempts to stimulate deiodination in mitochondrial preparations by reducing endogenous bound lipoamide were unsuccessful.
D000818:Animals; D001728:Dicumarol / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D007453:Iodide Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D009243:NAD / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D013696:Temperature; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D009243:NAD; C007409:dihydrolipoamide; D011441:Propylthiouracil; D008063:Thioctic Acid; D001728:Dicumarol; D010544:Peroxidases; D007453:Iodide Peroxidase; D004229:Dithiothreitol