Deiodinase

thyroxine 5'-deiodinase
Identifiers
EC number 1.97.1.10
CAS number 70712-46-8
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Deiodinase (or iodide peroxidase or "Monodeiodinase") is a peroxidase enzyme that is involved in the activation or deactivation of thyroid hormones.

Types

Types of deiodinases include:

family prosthetic group genes
Iodothyronine deiodinase DIO1, DIO2, DIO3
Iodotyrosine deiodinase Flavin mononucleotide (FMN) IYD

Iodotyrosine deiodinase contributes to breakdown of thyroid hormones. It releases iodine, for renewed use, from iodinated tyrosines resulting from catabolism of iodothyronines. Iodotyrosine deiodinase employs a flavin mononucleotide cofactor and belongs to the NADH oxidase/flavin reductase superfamily.[1]

Iodothyronine deiodinases catalyze release of iodine directly from the thyronine hormones. They are selenocysteine-dependent membrane proteins with a catalytic domain resembling Peroxiredoxins (Prx).[2] Three related isoforms, deiodinase type I, II, and III, contribute to activation and inactivation of the initially released hormone precursor T4 (thyroxine) into T3 (triiodothyronine) or rT3 (reverse triiodothyronine) in target cells. The enzymes catalyze a reductive elimination of iodine (the different isoforms attack different thyronine positions), thereby oxidizing themselves similar to Prx, followed by a reductive recycling of the enzyme.

Starvation response

In starvation, deiodinase (to be specific, Deiodinase I) is inhibited thus lowering basal metabolic rate. However, in the brain, heart, skeletal muscle and thyroid, this is not so, as these organs must maintain homeostasis (skeletal muscle through shivering can increase temperature). This is achieved by the latter organs expressing deiodinase II rather than Deiodinase I as in most peripheral tissues.

Selenium

Selenium which is the prosthetic group of iodotyrosine deiodinase, as selenocysteine, plays a crucial role in determining the free circulating levels of T3. Selenium deficiency can have implications in fall of T3 levels.

References

  1. Thomas, SR; et al. "Crystal structure of iodotyrosine deiodinase, a novel flavoprotein responsible for iodide salvage in thyroid glands.". J. Biol. Chem. 284: 19659–19667. doi:10.1074/jbc.M109.013458. PMC 2740591. PMID 19436071.
  2. Schweizer, U; Schlicker, C; Braun, D; Köhrle, J; Steegborn, C (Jul 2014). "Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism.". Proc Natl Acad Sci USA 111 (29): 10526–10531. doi:10.1073/pnas.1323873111. PMID 25002520.

External links


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