Rapid and selective inner ring deiodination of thyroxine sulfate by rat liver deiodinase
Previous studies have shown that the inner ring deiodination (IRD) of T3 and the outer ring deiodination (ORD) of 3,3'-diiodothyronine are greatly enhanced by sulfate conjugation. This study was undertaken to evaluate the effect of sulfation on T4 and rT3 deiodination. Iodothyronine sulfate conjugates were chemically synthetized. Deiodination was studied by reaction of rat liver microsomes with unlabeled or outer ring /sup 125/I-labeled sulfate conjugate at 37 C and pH 7.2 in the presence of 5 mM dithiothreitol. Products were analyzed by HPLC or after hydrolysis by specific RIAs. T4 sulfate (T4S) was rapidly degraded by IRD to rT3S, with an apparent Km of 0.3 microM and a maximum velocity (Vmax) of 530 pmol/min X mg protein. The Vmax to Km ratio of T4S IRD was increased 200-fold compared with that of T4 IRD. However, formation of T3S by ORD of T4S could not be observed. The rT3S formed was rapidly converted by ORD to 3,3'-T2 sulfate, with an apparent Km of 0.06 microM and a Vmax of 516 pmol/min X mg protein. The enzymic mechanism of the IRD of T4S was the same as that of the deiodination of nonsulfated iodothyronines, as shown by the kinetics of stimulation by dithiothreitol or inhibition by propylthiouracil. The IRD of T4S and the ORD of rT3 were equally affected by a number of competitive inhibitors, suggesting a single enzyme for the deiodination of native and sulfated iodothyronines. In conjunction with previous findings on the deiodination of T3S, these results suggest that sulfation leads to a rapid and irreversible inactivation of thyroid hormone.
- Research Organization:
- Erasmus Univ. Medical School, Rotterdam, Netherlands
- OSTI ID:
- 5254304
- Journal Information:
- Endocrinology; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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PEROXIDASES
ENZYME ACTIVITY
THYROXINE
DEIODINATION
BIOCHEMICAL REACTION KINETICS
IODINE 125
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MICROSOMES
RATS
SULFATES
TRACER TECHNIQUES
TRIIODOTHYRONINE
URACILS
AMINO ACIDS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DEHALOGENATION
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDE HORMONES
PORPHYRINS
PYRIMIDINES
RADIOISOTOPES
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
SULFUR COMPOUNDS
THYROID HORMONES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques