Abstract
The precise mechanism of the biosynthesis of thyroxine (T4) from diiodotyrosine (DIT) has not yet been established. Among various hypothesis on this coupling mechanism, the syntheses of T4 through the coupling of DIT and hydroxydiiodophenylpyruvic acid (DIHPPA) has been supported by more convincing evidences. The nonenzymic synthesis of T4 from DIT is reported in this paper.
1. The yield of DIHPPA was approximately 19% in an assay system containing DIT, pyridoxal and Manganous ion, nonenzymatically.
2. When the bovine thyroid microsome and H2O2 generating system or α-ketoglutarate were added to this assay system, DIHPPA was only slightly produced.
3. The effect of pyridoxal on the T4 formation was investigated in vivo. As to results of these experiments, the ratio of iodothyronine (T4+T3) and iodotyrosine (DIT+MIT) tended to decrease by in the thyroid gland of chronic VB6 deficient rats for 4 or 6 weeks. However, the ratio of DIT and monoiodotyrosine (MIT), and manganous content had no remarkable change. From the above results, it is indicated that the iodotyrosine coupling reaction is stimulated by pyridoxal.
4. The yield of T4 was 24% by the reaction between DIT and DIHPPA in the presence of oxygen for 1 hr. T4 yield from DIT by oxygen bubbling in an assay system containing DIT, pyridoxal and manganous ion was gradually increased for 4 hrs. and reached a maximum value (10%).
From the above data, it is concluded that the mechanism of T4 production from DIT in thyroid gland is as follows : (a) in the first step DIHPPA yields more nonenzymatically than enzymatically from DIT : (b) in the second step T4 yield is gradually developed in the presence of oxygen : (c) pyridoxal and manganous may play an important role in the synthesis of T4 from DIT in thyroid gland.
