Disease relevance of Tetraiodothyroacetic acid

• The results showed clearly, however, that Tetrac is less efficient for all parameters studied, namely induction of cardiac hypertrophy, alpha-myosin heavy chain mRNA, monodeiodinase type 1 activity and mRNA levels of the sarcoplasmic SERCA 2a [1].
• Euthyroid sick syndrome is possibly due to an increase in Triac (a T3 analogue) and/or Tetrac (a T4 analogue) [2].
• Triac and/or Tetrac possibly feed back on the pituitary/hypothalamus region and cause a secondary hypothyroidism [2].

High impact information on Tetraiodothyroacetic acid

• 3,3',5'-Triiodo-L-thyronine is the most potent natural substrate (IC50 = 0.3 microM) and tetraiodothyroacetic acid is the most potent inhibitor (IC50 = 0.2 microM) [3].
• T(4) action on ERalpha was inhibited by PD 98059, an inhibitor of ERK1/2 phosphorylation, and by tetraiodothyroacetic acid, a T(4) analog that blocks cell surface-initiated actions of T(4) but is not itself an agonist [4].
• This T(4) action was duplicated by T(4)-agarose and blocked by tetraiodothyroacetic acid, which inhibits binding of T(4) to plasma membranes [5].
• When preincubated with L-T4 for 24 h prior to IFN-gamma treatment, tetrac blocked L-T4 potentiation, but, when coincubated with L-T4 for 4 h after 20 h IFN-gamma, tetrac did not inhibit the L-T4 effect [6].
• In human serum, Tetrac was exclusively bound to T4-binding prealbumin [7].

Biological context of Tetraiodothyroacetic acid

• Scatchard plots revealed the protein to have a principal binding site with both high capacity and high affinity for tetrac (KA 4.8 X 10(10) M-1 [8].
• As judged from competitive binding studies, the protein also binds tetraiodothyropropionic acid (tetraprop) firmly, but less so than tetrac [8].
• During polyacrylamide gel electrophoresis at pH 8.0, the tetrac binding protein has a mobility characteristic of a prealbumin [8].
• Tetraiodothyroacetic acid (tetrac) decreased T4-induced acetylation of TR [9].
• The limited substrate specificity of rat liver ITH-D, which fulfills a major contribution in ITH-metabolism in vivo, may be of physiological relevance for the poorly characterized metabolism of naturally occurring (Tetrac) and pharmacologically important (D-T4) ITH-analogs [10].

Anatomical context of Tetraiodothyroacetic acid

• Labeled Triac* and/or Tetrac* were prominent among steady state metabolites of T3* or T4* in intestines, feces, and residual carcass, but not in liver or kidneys [11].
• Various thyroid hormones caused an increase in uridine uptake, with the rank order of potency 3,3',5-triiodothyroacetic acid greater than T3 greater than L-T4 greater than D-T4 approximately equal to 3,3',5,5'-tetraiodothyroacetic acid; rT3 was inactive [12].
• The relative affinity of the receptor for thyroid hormone analogs was triiodothyroacetic acid = T3 greater than T4 greater than tetraiodothyroacetic acid in oligodendrocyte and astrocyte nuclei, and the sedimentation coefficient of the receptor was approximately 3.8S in both cell types [13].
• High-affinity binding of reverse T3 and tetrac in nuclei of human lymphocytes [14].
• Effect of theophylline on binding of triiodothyronine, thyroxine, thyroxamine, tetraiodothyroacetic acid and cortisol in the cytosol of human leukocytes [15].

Associations of Tetraiodothyroacetic acid with other chemical compounds

• The concentration of hormone that produced 50% of maximal increase in K(+)-induced radioactivity release was 8 x 10(-9) M for T4 and 1.6 x 10(-8) M for T3 while 3,3',5,5'-tetraiodothyroacetic acid was almost ineffective [16].
• Among the analogues tested, binding - relative to T3 - of D-T3, triiodothyoacetic acid and desamino-T3 is the same for both classes of binding sites, but relative affinity of thyroxine, D-T4, tetraiodothyroacetic acid and desamino-T4 is 2.5 to 6 times higher for the second class of binding sites than for the first class [17].
• In this study, we have examined the metabolic clearance rate of tetraiodothyroacetic acid in rabbits given amiodarone (20 mg.kg-1.day-1 ip for 3 weeks) or saline (controls) [18].

Gene context of Tetraiodothyroacetic acid

• The crystal structure of the complex of human transthyretin (hTTR) with 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2 Angstrom resolution [19].
• Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1 and 1.8 A resolution [20].
• A free Tetrac concentration of 5 pM was equally effective as 50 pM free T4 in reducing the TSH response to TRH [7].
• The relative binding affinities of thyroid hormone analogs for T3 sites were as follows: TRIAC greater than T3 greater than TETRAC greater than T4 greater than reverse T3 greater than T2 [21].

Analytical, diagnostic and therapeutic context of Tetraiodothyroacetic acid

• Due to its rapid metabolic clearance rate, Triac is not suitable for TSH suppression and therefore the slowly metabolized 3,5,3',5'-tetraiodothyroacetic acid (Tetrac), the precursor of Triac, was studied [1].

References