Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sequential deiodination of thyroxine in rat liver homogenate.

ABSTRACT: Rat liver homogenate was incubated at 37 degrees C with thyroxine, 3,3',5-tri-iodothyronine, 3,3',5'-tri-iodothyronine or 3,3'-di-iodothyronine. The degradation or accumulation of these compounds was measured by specific radioimmunoassays. (1) Production of 3,3',5-tri-iodothyronine from thyroxine was highest at pH 6.0--6.5 and was markedly stimulated by the addition of dithiothreitol and effectively inhibited in the presence of 6-propyl-2-thiouracil. (2) Accumulation of 3,3',5'-tri-iodothyronine on incubation of thyroxine with homogenate was only observed above pH 8.5. Otherwise the product was converted into 3,3'-di-iodothyronine too rapidly to allow its measurement. By measuring 3,3'-di-iodothyronine it was deduced that 5-deiodination of thyroxine was most effective at approx. pH 8.0. Dithiothreitol powerfully stimulated this reaction and 6-propyl-2-thiouracil strongly inhibited. (3) Monodeiodination of the tyrosine ring of 3,3',5-tri-iodothyronine was the slowest reaction, was optimal at pH 8.0 and was less affected by dithiothreitol and 6-propyl-2-thiouracil than the above reactions. (4) 5'-Deiodination of 3,3',5'-tri-iodothyronine was extremely rapid, with a pH optimum probably at about 6.5. Owing to the high reaction rate under the conditions used it was not possible to assess the effects of dithiothreitol and 6-propyl-2-thiouracil.

SUBMITTER: Visser TJ

PROVIDER: S-EPMC1185902 | biostudies-other | 1978 Jul

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Inhibition of hepatic deiodination of thyroxine is caused by selenium deficiency in rats.

Project description:Selenium (Se) deficiency produced up to a 14-fold decrease in hepatic tri-iodothyronine (T3) production from thyroxine (T4) in vitro. The T3 production rate could not be restored by the addition of a variety of cofactors, nor by the addition of control homogenate. The impairment in hepatic T3 production observed in Se deficiency was reflected in the concentrations of thyroid hormones circulating in plasma, T4 being increased approx. 40% and T3 being decreased by 30%. However, the fall in plasma T3 concentrations was smaller than might be expected in view of the marked decreased in T3 production. Se deficiency had no measurable effect on plasma reverse-tri-iodothyronine concentrations. The data suggest that Se deficiency produces an inhibition of both 5- and 5'-deiodination, consistent with the widely held view that these reactions are catalysed by the same enzyme complex. The mechanism of inhibition appears not be mediated by changes in thiol levels, but a direct role of Se in the activity of the deiodinase complex cannot be excluded.

| S-EPMC1148561 | biostudies-other

5-HYDROXYTRYPTAMINE METABOLISM BY THE NUCLEAR FRACTION OF RAT-LIVER HOMOGENATE.

Project description:1. The metabolism of 5-hydroxy[1'-(14)C]tryptamine creatinine sulphate in the nuclear fraction of rat-liver homogenate was studied. In the incubation mixture five metabolites were found. 2. Two metabolites were not radioactive; one of them was identified as 5-hydroxyindole-3-carboxylic acid and the second tentatively as 5-hydroxyindole-3-aldehyde. 3. 5-Hydroxyindol-3-ylacetic acid, 1'-N-acetyl-5-hydroxytryptamine and 5-hydroxytryptophol were not precursors of 5-hydroxyindolealdehyde and 5-hydroxyindolecarboxylic acid. 4. It was shown that the metabolism of 5-hydroxytryptamine in the nuclear fraction involves monoamine oxidase, the precursor of 5-hydroxyindolealdehyde and 5-hydroxyindolecarboxylic acid being most probably 5-hydroxyindol-3-ylacetaldehyde.

| S-EPMC1206536 | biostudies-other

The function of subcellular fractions in the oxidation of glutathione in rat liver homogenate.

Project description:1. The aerobic loss of GSH added to the supernatant fraction from rat liver is much increased by including the microsome fraction, which both inhibits the concurrent reduction of the GSSG formed and also augments the net oxidation rate. 2. Oxidation occurs with a mixture of dialysed supernatant and a protein-free filtrate; the latter is replaceable by hypoxanthine and the former by xanthine oxidase, whereas fractions lacking this enzyme give no oxidation. 3. In all these instances augmentation occurs with microsomes, with fractions having urate oxidase activity and with the purified enzyme; uric acid and microsomes alone also support the oxidation. 4. Evidence implicating additional protein factors is discussed. 5. It is suggested that GSH oxidation by homogenate is linked through glutathione peroxidase to the reaction of endogenous substrate with supernatant xanthine oxidase and of the uric acid formed with peroxisomal urate oxidase.

| S-EPMC1179055 | biostudies-other

Neonatal thyroxine activation modifies epigenetic programming of the liver.

Project description:The type 2 deiodinase (D2) in the neonatal liver accelerates local thyroid hormone triiodothyronine (T3) production and expression of T3-responsive genes. Here we show that this surge in T3 permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increases H3K9me3 levels during post-natal days 1-5 (P1-P5), and results in methylation of 1,508 DNA sites (H-sites) in the adult mouse liver. These sites are associated with 1,551 areas of reduced chromatin accessibility (RCA) within core promoters and 2,426 within intergenic regions, with reduction in the expression of 1,363 genes. There is strong spatial correlation between density of H-sites and RCA sites. Chromosome conformation capture (Hi-C) data reveals a set of 81 repressed genes with a promoter RCA in contact with an intergenic RCA ~300 Kbp apart, within the same topologically associating domain (χ2 = 777; p < 0.00001). These data explain how the systemic hormone T3 acts locally during development to define future expression of hepatic genes.

| S-EPMC8295303 | biostudies-literature

Effects of thyroxine on the synthesis of folate coenzymes in rat liver.

Project description:1. The effects of thyroidectomy and of ;acute' and ;chronic' administration of thyroxine on the synthesis of folate coenzymes were studied by determining the liver contents of folate active derivatives and the enzymic activities involved in their biosynthesis. The effect of thyroxine on the same enzymes in vitro was also studied. 2. In thyroidectomized rats the liver contents of folate coenzymes did not change except for a slight decrease in the contents of 5-formyltetrahydrofolate and tetrahydrofolate compared with those in control rats. 3. In the same animals serine hydroxymethyltransferase and formyltetrahydrofolate synthetase activities decreased markedly. 4. The ;chronic' administration of thyroxine to thyroidectomized rats caused more evident variations in the liver contents of folate coenzymes and in particular a decrease in the contents of 5-formyltetrahydrofolate, tetrahydrofolate, 5(or 10)-formyl derivatives of tetrahydropteroylpolyglutamate and of 5(or 10)-formyl derivatives of pteroylpolyglutamate. 5. The enzymic activities did not show significant variations. 6. The ;acute' administration of thyroxine caused changes in the liver contents of some folate derivatives such as 10-formyldihydrofolate, 10-formylfolate, tetrahydrofolate and the 10-formyl derivative of dihydropteroylpolyglutamate. In these animals also the enzymic activities were unchanged. 7. No effect of thyroxine on enzymic activities in vitro was observed.

| S-EPMC1185348 | biostudies-other

Neonatal Thyroxine Activation Modifies Epigenetic Programming Of The Liver

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-18 | GSE162930 | GEO

Deiodination of L-thyroxine and its activity on the oxidation in vitro of reduced nicotinamide-adenine dinucleotide by peroxidase plus hydrogen peroxide.

Project description:When l-thyroxine activates the oxidation of NADH by peroxidase+H(2)O(2), little removal of phenolic-ring iodine atoms becomes apparent until most of the NADH has been oxidized, after which it increases markedly. This extensive deiodination is accompanied by loss of the ability of thyroxine to catalyse the oxidation of NADH by peroxidase+H(2)O(2). The slight deiodination observed before the appearance of extensive deiodination is somewhat higher when the effect of thyroxine on NADH oxidation is greater, and lower when thyroxine has exerted a slighter effect. ICN (but not I(2) or thyronine) catalyses NADH oxidation, in both the presence and the absence of peroxidase+H(2)O(2): thyroxine+peroxidase+H(2)O(2) are thus comparable with ICN alone in their effects on NADH oxidation. The obvious conclusion from the above observation, namely that the active moiety is the halogen liberated from thyroxine (or ICN) is, however, not directly supported by some of the results obtained by measuring the degree of deiodination of thyroxine in the system. In an attempt to reconcile some apparently contradictory conclusions, it is suggested that, when thyroxine activates oxidation of NADH by peroxidase+H(2)O(2), the diphenyl ether structure is undergoing cyclic deiodination and iodination. This would be accompanied by the maintenance in the reaction medium of an oxidized form of iodine, similar to that liberated by ICN, which would be the actual active moiety, until the NADH concentration becomes so low that the diphenyl ether structure is ruptured oxidatively. An alternative explanation is that thyroxine is oxidized to a form that either oxidizes NADH or loses iodine in competing reactions.

| S-EPMC1178193 | biostudies-other

The sensitivity of acetyl-coenzyme A carboxylase to citrate stimulation in a homogenate of rat liver containing subcellular particles.

Project description:1. Although citrate is known to activate purified preparations of acetyl-CoA carboxylase, it had no stimulatory effect on the incorporation of [(14)C]acetate into long-chain fatty acids in a whole homogenate of rat liver (S(0.7)) under conditions in which the activity of acetyl-CoA carboxylase was rate-limiting for fatty acid synthesis. 2. The rate of incorporation of acetyl carbon into fatty acids was estimated in S(0.7) preparations incubated with [(14)C]acetate, by measuring the specific radioactivity of the acetyl carbon of acetyl-CoA and the incorporation of (14)C into fatty acids. These estimates were compared with estimates of acetyl-CoA carboxylase activity in the S(0.7) preparation obtained by direct assay in conditions in which the enzyme was in the fully activated state. 3. In the absence of citrate, incorporation of acetyl carbon into fatty acids was about 75% of the value expected if the acetyl-CoA carboxylase in the S(0.7) preparation were in the fully activated state. 4. Incorporation of acetyl carbon into fatty acids in the S(0.7) preparation was stimulated by citrate, but the effect was many times less than the stimulation of [(14)C]acetate incorporation by citrate in particle-free preparations. 5. When the mitochondria and microsomes were removed from the S(0.7) preparation, [(14)C]acetate incorporation into fatty acids fell to a negligible value and the preparation became highly sensitive to stimulation by citrate. 6. It is suggested that in the presence of mitochondria and microsomes, and in the intact liver cell, the degree of activation of acetyl-CoA carboxylase is such that citrate activation may not be of physiological significance.

| S-EPMC1178872 | biostudies-other

Evidence for a single enzyme in rat liver catalysing the deiodination of the tyrosyl and the phenolic ring of iodothyronines.

Project description:The enzymic 5'-deiodination of 3',5'-di-iodothyronine and 5-deiodination of 3,3',5-tri-iodothyronine by rat liver microsomal fractions were found to be characterized by apparent Km values of 0.77 and 17.4 microM respectively, 3',5'-Di-iodothyronine was a competitive inhibitor of 3,3',5-tri-iodothyronine 5-deiodination (Ki 0.65 microM) and 3,3',5-tri-iodothyronine was a competitive inhibitor of 3',5'-di-iodothyronine 5'-deiodination (Ki 19.6 microM). In addition, several radiographic contrast agents and iodothyronine analogues inhibited both reactions competitively and with equal potencies (r = 0.999). These results strongly suggest the existence of a single hepatic deiodinase acting on both the tyrosyl and phenolic ring of iodothyronines.

| S-EPMC1163699 | biostudies-other

Oyster homogenate

Project description:Insights into the enrichment dynamics of Oysters using shotgun metagenomics.

| PRJNA498955 | ENA