Thyronamines are isozyme-specific substrates of deiodinases

Area of Science:

• Biochemistry
• Endocrinology
• Molecular Biology

Background:

• Thyronamines (TAMs) are novel signaling molecules structurally related to thyroid hormones.
• TAMs antagonize thyroid hormone actions, suggesting distinct biological roles.
• Proposed biosynthesis of TAMs involves decarboxylation and deiodination of thyroid hormones.

Purpose of the Study:

• To investigate if deiodinases (Dio1, Dio2, Dio3) can metabolize thyronamines.
• To determine the substrate specificity of deiodinases for different thyronamine structures.
• To assess the role of deiodinases in the biosynthesis of thyronamines.

Main Methods:

• Incubation of various thyronamines with isozyme-specific deiodinase preparations.
• Analysis of deiodination products using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Functional competition assays to confirm deiodinase substrate activity.

Main Results:

• Dio1 deiodinated phenolic and tyrosyl rings of several thyronamines, inhibited by PTU.
• Dio2 deiodinated phenolic rings of rT3AM and 3',5'-T2AM in a PTU-insensitive manner.
• Dio3 deiodinated thyronamines with tyrosyl ring iodine atoms; competition assays validated substrate roles.

Conclusions:

• Deiodinases demonstrate the ability to metabolize thyronamines.
• These findings support a role for deiodinases in the biosynthesis of thyronamines.
• The study helps elucidate the metabolic pathways for thyronamine formation.