Open AccessMechanism of Thyroxine Formation from Diiodotyrosine and p ‐Hydroxydiiodophenylpyruvic Acid
Author(s) -
Blasi F.,
Fragomele F.,
Covelli I.
Publication year - 1968
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1968.tb00360.x
Subject(s) - diiodotyrosine , chemistry , iodide , radical , oxygen , yield (engineering) , peroxide , hydrogen peroxide , iodine , reaction mechanism , inorganic chemistry , photochemistry , medicinal chemistry , organic chemistry , catalysis , biochemistry , hormone , triiodothyronine , materials science , metallurgy
1 The mechanisms of the non‐enzymic synthesis of thyroxine from diiodotyrosine and its keto acid derivative 4‐hydroxy‐3,5‐diiodophenylpyruvic acid has been investigated. 2 The time course of the overall coupling process has been studied by following the formation of thyroxine and the disappearance of the reactants from the incubation medium. Thyroxine formation has a lag phase during which diiodotyrosine remains unchanged, whereas 4‐hydroxy‐3,5‐diiodophenylpyruvic acid disappears very rapidly. 3 Disappearance of 4‐hydroxy‐3,5‐diiodophenylpyruvic acid from the reaction mixture is due to the formation, besides of a degradation product, of an oxidized form of the keto acid which reacts with diiodotyrosine without a lag phase even in the absence of oxygen. This oxidized intermediate is formed by the uptake of 2 atoms of oxygen per mole of the keto acid. Its spectrum in the ultraviolet region is very similar to that of the unmodified keto acid; furthermore it is stabilized by borate ions and is able to oxidize iodide. The most likely structure of the oxidized intermediate of the 4‐hydroxy‐3,5‐diiodophenylpyruvic acid, therefore, is that of a peroxide. 4 Propylgallate, a radical scavenger known to block free radicals originated from 4‐hydroxy‐3,5‐diiodophenylpyruvic acid, increases the lag phase, inhibits the oxygen uptake 4‐hydroxy‐3,5‐diiodophenylpyruvic acid and decreases the overall yield of thyroxine if added during the lag phase; it is uneffective when added during the anaerobic period of the coupling reaction. 5 The following mechanism can be envisaged: (a) in a first step 4‐hydroxy‐3,5‐diiodophenyl‐pyruvic acid looses an electron thus originating a free radical; (b) in a second step 2 atoms of oxygen are taken up by the free radical and a peroxide‐like derivative is formed; (c) in the third step, not requiring the presence of oxygen, the peroxide derivative of the keto acid instantly couples with diiodotyrosine to form thyroxine.