Investigation of type I and type III iodothyronine deiodinases in rat tissues using N-bromoacetyl-iodothyronine affinity labels

Schoenmakers, Christian H.H.; Pigmans, Ingrid G.A.J.; Visser, Theo J.

doi:10.1016/0303-7207(94)03440-5

Cited by 24 publications

(21 citation statements)

References 47 publications

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“…In addition, there is 47% similarity with the bifunctional (5' or 5 deiodination) human Dl enzyme which is especially high in the region surrounding the selenocysteine residue ( 11). to extraction from microsomal membranes by high pH (35). Hydropathy analysis of the predicted protein revealed a highly hydrophobic amino terminal region of about 40 amino acids which is the only portion of the protein which can qualify as a membrane spanning domain (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.

Salvatore¹,

Low²,

Berry³

et al. 1995

J. Clin. Invest.

179

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Type 3 iodothyronine deiodinase (D3) catalyzes the conversion of T4 and T3 to inactive metabolites. It is highly expressed in placenta and thus can regulate circulating fetal thyroid hormone concentrations throughout gestation. We have cloned and expressed a 2.1-kb human placental D3 cDNA which encodes a 32-kD protein with a Km of 1.2 nM for 5 deiodination of T3 and 340 nM for 5' deiodination of reverse T3. The reaction requires DTT and is not inhibited by 6n-propylthiouracil. We quantitated transiently expressed D3 by specifically labeling the protein with bromoacetyl [12"'I T3. The KatIK. ratio for 5 deiodination of T3 was over 1,000-fold that for 5' deiodination of reverse T3. Human D3 is a selenoenzyme as evidenced by (a) the presence of an in frame UGA codon at position 144, (b) the synthesis of a 32-kD 75Se-labeled protein in D3 cDNA transfected cells, and (c) the presence of a selenocysteine insertion sequence element in the 3' untranslated region of the mRNA which is required for its expression. The D3 selenocysteine insertion sequence element is more potent than that in the type 1 deiodinase or glutathione peroxidase gene, suggesting a high priority for selenocysteine incorporation into this enzyme. The conservation of this enzyme from Xenopus laevis tadpoles to humans implies an essential role for regulation of thyroid hormone inactivation during embryological development. (J. Clin. Invest. 1995. 96:2421-2430

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that BrAcT3 is an excellent affinity label for the Dl enzyme (29,31,40). On the other hand, similar techniques were unsuccessful in achieving specific labeling of D3 in rat brain microsomes (35) (Fig. 9).…”

Section: Discussionmentioning

confidence: 99%

Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.

Salvatore¹,

Low²,

Berry³

et al. 1995

J. Clin. Invest.

179

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“…In addition to the importance of the D1 and D2 in converting T 4 to T 3 in peripheral tissues, these enzymes are also highly expressed in the thyroid gland (Leonard & Visser 1986, Toyoda et al 1992, Schoenmakers et al 1995, Salvatore et al 1996, Leonard et al 2001. D1 seems to be constitutively expressed in the human thyroid gland, whereas D2 expression varies closely with the degree of thyroid stimulation (Salvatore et al 1996).…”

Section: Role Of D1 Deiodinase In Thyroid Hormone Activation and Inacmentioning

confidence: 99%

Type 1 iodothyronine deiodinase in human physiology and disease

Maia

Goemann²,

Meyer³

et al. 2011

Journal of Endocrinology

194

123

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Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T 4 ) molecule, thus producing either the active form triiodothyronine (T 3 ; activation) or inactive metabolites (reverse T 3 ; inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T 3 production contributes to a portion of plasma T 3 in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T 3 concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

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“…D3 is an integral membrane protein, resistant to extraction from microsomal membranes by high pH (Visser et al 1979, Schoenmakers et al 1995. Endogenous D3 protein is expressed, by immunohistochemistry, on the plasma membrane of NCLP-6E cells (Baqui et al 2000), whereas intracellularly it colocalizes with the endosomal marker EEA-1 and clathrin, and not with the two ER-resident proteins BiP and calnexin (Baqui et al 2003).…”

Section: Type 3 Iodothyronine Deiodinasementioning

confidence: 99%

Local impact of thyroid hormone inactivation

Dentice¹,

Salvatore²

2011

Journal of Endocrinology

119

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Deiodination is a critical process by which the minimally active thyroxine (T 4 ) molecule is converted into the favorite ligand for thyroid hormone (TH) receptors, triiodothyronine (T 3 ). The iodothyronine deiodinases type 1, 2, and 3 (D1, D2, and D3) constitute a potent mechanism of TH activation (D1 and D2) or inactivation (D3), which functions by tissue specifically regulating TH bioavailability. D2 and D3 are widely expressed and in a dynamically and tightly coordinated fashion, thereby allowing cells to customize their own TH activity. D3, the major T 3 and T 4 inactivating deiodinase, catalyzes their conversion to 3,3 0 -diiodothyronine and to reverse T 3 respectively. According to common wisdom, D3 plays a major role in lowering serum TH concentrations during development, as supported by the much wider D3 tissue expression in the embryo structures than in the adult tissues. However, several recent studies show that D3 is reexpressed in adult life in various pathophysiological contexts, which strengthens the concept that cell-specific TH inactivation is a critical mediator in cellular TH metabolism. This review focuses on the progress made in understanding the physiological function and significance of D3. It summarizes the intriguing evidence that D3 plays a pivotal role in defining local TH concentration in the developing fetus and in several conditions in adult life.

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Investigation of type I and type III iodothyronine deiodinases in rat tissues using N-bromoacetyl-iodothyronine affinity labels

Cited by 24 publications

References 47 publications

Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.

Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.

Type 1 iodothyronine deiodinase in human physiology and disease

Local impact of thyroid hormone inactivation

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