Conversion of T3 and rT3 to 3,3'-T2: pH dependency

Area of Science:

• Biochemistry
• Endocrinology
• Enzymology

Background:

• Extrathyroidal deiodination of thyroxine (T4) produces triiodothyronine (T3) and reverse triiodothyronine (rT3), crucial for peripheral thyroid hormone action.
• The deiodination product 3,3 -diodothyronine (3,3 -T2) is derived from both T3 and rT3.

Purpose of the Study:

• To characterize the enzymatic reactions involved in the conversion of T3 and rT3 to 3,3 -T2.
• To investigate the degradation of 3,3 -T2 in rat liver homogenate.
• To elucidate the role of pH in these deiodination processes and their impact on thyroid hormone regulation.

Main Methods:

• Development of a specific radioimmunoassay for 3,3 -T2.
• Enzymatic assays using rat liver homogenate to study deiodination reactions.
• Analysis of pH activity profiles and kinetic parameters (KM, reaction velocity).

Main Results:

• The conversion of T3 to 3,3 -T2 is slower than T4 to T3 conversion, with optimal activity at pH 8.4.
• The conversion of rT3 to 3,3 -T2 is rapid (KM = 4 x 10(-7) M) and favored in acidic pH.
• 3,3 -T2 deiodination is faster in acidic conditions, primarily yielding 3-monoiodothyronine (3-T1).

Conclusions:

• Outer ring deiodination of T4 is favored in acidic conditions, while inner ring deiodination occurs in alkaline conditions.
• pH-dependent accumulation of T3 (acidic) or rT3 (alkaline) can occur, influencing T4 5 -deiodination.
• pH shifts represent a regulatory mechanism for peripheral thyroid hormone activity, modulating the inhibitory effects of rT3.