Rate Of Deiodination Research Articles

Prolactin-thyroid interaction in Fundulus heteroclitus

Injections of adult Fundulus heteroclitus with 0.2 IU of oTSH over 4 days caused an increase in serum T 4, with no effect on serum T 3. Administration of 12 IU of oPRL in conjunction with the same dosage of TSH prevented the TSH-induced rise in T 4, without affecting serum T 3 levels. The failure of TSH to cause T 4 levels to rise in the presence of PRL may result from either inhibition of release or acceleration of metabolic clearance of T 4. We therefore conducted three experiments to examine potential effects of PRL on the kinetics of peripheral clearance of thyroid hormones. 125I T 4 was cleared from serum in a biphasic pattern that was unaltered by PRL. Clearance of labeled T 3 followed a similar pattern that was also not influenced by PRL treatment. Generation of labeled T3 by deiodination of a dose of 125I T 4 was quantified over a 24-h period. Again, PRL-treated fish showed no significant differences. Since PRL is without effects on thyroid hormone clearance patterns or deiodination rate, we conclude that PRL prevents TSH-induced increases in serum T 4 in this species by directly affecting thyroid function.

Evidence for two pathways of iodothyronine 5'-deiodination in rat pituitary that differ in kinetics, propylthiouracil sensitivity, and response to hypothyroidism.

We have studied 5'-deiodination of thyroxine (T(4)) and 3,3',5'-triiodothyronine (rT(3)) in rat pituitary tissue in vitro, with respect to substrate specificity, reaction kinetics, effects of 6-n-propyl-2-thiouracil (PTU), and the time course of effects of thyroid hormone depletion and repletion. Removal of one phenolic iodine or both tyrosyl iodines from the T(4) molecule resulted in compounds that were not deiodinated, but alterations in the alanine side chain had little effect.5'-Deiodination of 2 nM rT(3) by pituitary microsomes from euthyroid rats was inhibited >90% by 1 mM PTU, but was inhibited <10% by 100 nM T(4). The apparent Michaelis constant (K(m)) and maximum velocity (V(max)) for rT(3) at 20 mM dithiothreitol (DTT) were 33 nM and 84 pmol/mg protein per h. This reaction followed ping-pong type reaction kinetics when concentrations of DTT were varied. PTU inhibition was competitive with DTT and uncompetitive with rT(3). In contrast, when pituitary microsomes from hypothyroid rats (21 d postthyroidectomy) were used, deiodination of 2 nM rT(3) was inhibited only 20% by 1 mM PTU and up to 80% by 100 nM T(4). At 20 mM DTT, the apparent K(m) and V(max) in hypothyroid microsomes were 4.7 nM rT(3) and 16 pmol/mg protein per h. T(4) was a competitive inhibitor of PTU-insensitive rT(3) 5'-deiodination (K(i) = 1.3 nM). T(4) 5'-deiodination by hypothyroid microsomes was not affected by PTU, was competitively inhibited by rT(3) (K(i), 1.7 nM), and exhibited sequential type reaction kinetics with DTT as cosubstrate. When T(4) 5'-deiodination was measured in euthyroid and hypothyroid microsomes, respectively, the apparent K(m) and V(max) for T(4) at 20 mM DTT, were 0.9 nM and 0.55 pmol/mg protein per h (euthyroid), and 0.8 nM and 6.9 pmol/mg protein per h (hypothyroid). The T(4) 5'-deiodination rate and the PTU-insensitive, but not total, rT(3) 5'-deiodination rate (i.e. measured in the presence and the absence of 1 mM PTU, respectively) in pituitary homogenates were significantly elevated 24 h after thyroidectomy. PTU-insensitive activity continued to increase until at >/=30 d after thyroidectomy it was 11 times the PTU-insensitive activity in controls. At the latter time, PTU-sensitive rT(3) 5'-deiodinase activity appeared to be decreased. The increase in PTU-insensitive T(4) and rT(3) 5'-deiodination observed 48 h after thyroidectomy was prevented by replacement doses of T(4) or T(3). The PTU-insensitive activity of long term hypothyroid pituitaries was decreased by 71% and >/=84% 4 h after injection of 20 and 200 mug T(3), respectively, with no change in PTU-sensitive rT(3) deiodination. These data show that rat pituitary tissue contains two distinct iodothyronine 5'-deiodinating pathways that differ with respect to substrate specificity, PTU sensitivity, reaction kinetics, and regulation by thyroid hormone. One of these resembles the 5'-deiodinase of liver and kidney, and predominates in euthyroid pituitary tissue in vitro. The other, also found in rat brain, predominates in hypothyroid pituitary tissue, is rapidly responsive to changes in thyroid hormone availability, and, as judged by previous, in vivo studies, appears to account for all the T(3) produced locally in the pituitary and, thereby, 50% of the intracellular T(3) in this tissue.

Characteristics of iodothyronine tyrosyl ring deiodination by rat cerebral cortical microsomes.

We studied the biochemical properties of tyrosyl ring (5-) deiodination of L-T3 and L-T4 by cerebrocortical microsomes from euthyroid rats. Incubations contained radioiodinated L-T3) or L-T4 and dithiothreitol (DTT), and products were analyzed by paper chromatography. The pH maximum was 7.5 for 5-deiodination of both T3 and T4. Increasing the DTT concentration from 5 to 200 mM caused a progressive increase in the 5- deiodination rate of 2 nM T3, but at 500 mM DTT the rate decreased. When three DTT concentrations (5.25, 10.1, and 20.1 mM) were used, double reciprocal plots of 5-deiodination rate as a function of T3 concentration (from 0.3–40 nM) showed a sequential type kinetic pattern, with a limiting Kn of 1.7 nM L-T3. Cerebral microsomes from 4-day-old rats had an apparent Km for L-T3 similar to that of cerebrocortical microsomes from adult rats, but the neonatal tissues had a 3.5- to 10-fold higher apparent maximum velocity. At 50 mM DTT, L-T3 and L-T4 each inhibited 5-deiodination of the other. The ap...

Action spectra for the photolysis of 5-iododeoxyuridine in DNA and related model systems: evidence for short-range energy transfer.

Abstract— A variety of polynucleotides containing 5‐iodouracil residues were irradiated in aqueous solution with wavelengths between 240 and 313 nm. From the rate of deiodination the photochemical cross sections (aB) were determined as a function of the irradiation wavelength (A). The expression was used to relate the observed values of B to the intrinsic quantum yield, φINT, and to the absorption cross sections, and for the iodinated and noniodinated residues, respectively. φINT is the probability an excited iodouracil residue will deiodinate, while the parameter b is a measure of the number of noniodinated bases which contribute their excitation energy to the deiodination process. For IdUrd and poly(5‐iodouridylic acid), the average values of φINT calculated from the experimental B values were 0.0202 and 0.0188, respectively, for irradiation in air. In native, denatured, and depurinated DNA in which IdUrd was substituted for 10% of the Thd, the average φINT values were 0.0069, 0.0088, and 0.0153, respectively, indicating an enhancement in φINT upon decreasing the order of the polynucleotide. In contrast, the average values of b bor the same set of compounds were found to be4, 2 and 0.4, respectively, indicating a decrease in b with decreasing polynucleotide order, i.e. a loss of base stacking decreases the extent of energy transfer. A value of b= 4 for native DNA is assumed to mean that the extent of energy transfer in native DNA is limited to four base donors per iodouracil residue serving as an energy trap.

PH-dependency of iodothyronine metabolism in isolated perfused rat liver.

1. Isolated livers from fed male rats were perfused for 2 h with T4 (L-thyroxine), T3 (L-3,3',5-tri-iodothyronine) or rT3 (L-3,3',5'-tri-iodothyronine) at different pH values (7.1--7.6) in a fully synthetic medium, whereby normal metabolic functions were maintained without addition of rat blood constituents or albumin. 2. T3 output into the medium and net T3 production reached a maximum at a pH of the medium of 7.2 and significantly decreased with alteration of the pH when livers were perfused with T4 as a substrate. 3. However, the net T4 and T3 uptake by the liver, as well as the hepatic T4 and T3 content after perfusion, were not dependent on the pH of the perfusion when livers were offered T4 or T3 as substrates respectively. 4. Determination of intracellular pH by the analysis of the distribution of the weak acid dimethyloxazolidinedione allows the conclusion that the pH optimum of iodothyronine 5'-deiodinase in the intact perfused liver corresponds to the maximum determined in vitro for the membrane-bound enzyme localized in the endoplasmic reticulum. 5. The rapid 5'-deiodination of rT3 to 3,3'-T2 (L-3,3'-di-iodothyronine), the fast disappearance of 3,3'-T2, and the fact that no net rT3 production from T4 could be detected, supports the hypothesis that in rat liver iodothyronine 5'-deiodinase activity seems to predominate over iodothyronine 5-deiodinase activity. 6. Thus the rat liver can be considered in normal physiological situations as an organ forming T3 from T4 and deiodinating rT3 originating from extrahepatic tissues, whereby the cellular iodothyronine 5'-deiodination rate is controlled by the intracellular pH.

Peripheral serum thyroxine, triiodothyronine and reverse triiodothyronine kinetics in the low thyroxine state of acute nonthyroidal illnesses. A noncompartmental analysis.

The low thyroxine (T(4)) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T(4) and triiodothyronine (T(3)) with elevated reverse T(3) (rT(3)) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T(4), T(3), or rT(3) were determined in 16 patients with the low T(4) state and compared with 27 euthyroid controls and a single subject with near absence of thyroxine-binding globulin. Marked increases in the serum free fractions of T(4) (0.070+/-0.007%, normal [nl] 0.0315+/-0.0014, P < 0.001), T(3) (0.696+/-0.065%, nl 0.310+/-0.034, P < 0.001), and rT(3) (0.404+/-0.051%, nl 0.133+/-0.007, P < 0.001) by equilibrium dialysis were observed indicating impaired serum binding. Noncompartmental analysis of the kinetic data revealed an increased metabolic clearance rate (MCR) of T(4) (1.69+/-0.22 liter/d per m(2), nl 0.73+/-0.05, P < 0.001) and fractional catabolic rate (FCR) (32.8+/-2.6%, nl 12.0+/-0.8, P < 0.001), analogous to the euthyroid subject with low thyroxine-binding globulin. However, the reduced rate of T(4) exit from the serum (Kii) (15.2+/-4.6 d(-1), nl 28.4+/-3.9, P < 0.001) indicated an impairment of extravascular T(4) binding that exceeded the serum binding defect. This defect did not apparently reduce the availability of T(4) to sites of disposal as reflected by the increased fractional disposal rate of T(4) (0.101+/-0.018 d(-1), nl 0.021+/-0.003, P < 0.001). The decreased serum T(3) binding was associated with the expected increases in MCR (18.80+/-2.22 liter/d per m(2), nl 13.74+/-1.30, P < 0.05) and total volume of distribution (26.55+/-4.80 liter/m(2), nl 13.10+/-2.54, P < 0.01). However, the unaltered Kii suggested an extravascular binding impairment comparable to that found in serum. The decreased T(3) production rate (6.34+/-0.53 mug/d per m(2), nl 23.47+/-2.12, P < 0.005) appeared to result from reduced peripheral T(4) to T(3) conversion because of decreased 5'-deiodination rather than from a decreased T(4) availability. This view was supported by the normality of the rT(3) production rate. The normal Kii values for rT(3) indicated a comparable defect in serum and extravascular rT(3) binding. The reduced MCR (25.05+/-6.03 liter/d per m(2), nl 59.96+/-8.56, P < 0.005) and FCR (191.0+/-41.19%, nl 628.0+/-199.0, P < 0.02) for rT(3) are compatible with an impairment of the rT(3) deiodination rate. These alterations in thyroid hormones indices and kinetic parameters for T(4), T(3), and rT(3) in the low T(4) state of acute nonthyroidal illnesses can be accounted for by: (a) decreased binding of T(4), T(3), and rT(3) to vascular and extravascular sites with a proportionately greater impairment of extravascular T(4) binding, and (b) impaired 5'-deiodination activity affecting both T(4) and rT(3) metabolism.

Proposed mechanism for increased thyroxine deiodination in cold-acclimated rats.

Groups of male rats were administered isoproterenol (ISO), thyroxine (T4), or both (ISO + T4) daily for 20 days in an attempt to mimic the effect of cold acclimation on the rate of outer-ring deiodination of T4 to triiodothyronine (T3) by 2,000-g supernatants of homogenates of liver and kidney. The rates of hepatic and renal deiodination of T4 to T3 in an additional group of rats exposed to 4 +/- 1 degree C for 20 days were 53 and 71% higher, respectively, than control. Administration of ISO (100 micrograms . kg-1 . day-1) did not affect the rate of deiodination of T4 to T3 by either hepatic or renal tissue. Administration of T4 (50 micrograms . kg-1 . day-1) resulted in rates of hepatic and renal deiodination of T4 that were 297 and 222% higher, respectively, than control. Administration of ISO + T4 resulted in a rate of conversion of T4 to T3 not significantly different from that observed when T4 was administered alone. Serum concentration of T4 was elevated after administration of both T4 and ISO + T4, whereas serum concentration of T3 was elevated significantly above that of control only in the cold-acclimated group. These results suggest that the increased rate of 5'-monodeiodination of T4 by hepatic and renal homogenates from cold-acclimated rats is not a result of increased beta-adrenergic activity but can be accounted for by the increase in thyroid activity observed in these animals.

Extrathyroidal Effects of Low Concentrations of Thiourea on Rainbow Trout, Salmo gairdneri

Chronic exposure of fed immature rainbow trout (Salmo gairdneri) to a low ambient thiourea (TU) concentration did not depress circulating levels of T4 (thyroxine) or triiodothyronine, T4 degradation rate, or T4 deiodination rate indicating no significant T4 influence on thyroidal hormone output. However, TU increased the hematocrit and decreased distribution spaces for iodide and T4, indicating direct sensitivity of extrathyroidal processes to TU.Key words: thiourea, thyroxine, hematocrit, iodide metabolism, rainbow trout

The effect of 3-amino-1,2,4-triazole on hepatic and renal deiodination of l-thyroxine to 3,5,3′-triiodothyronine

An in vitro model has been employed to evaluate the effects of administration of aminotriazole (ATZ) both in vivo and in vitro on the rate of outer-ring deiodination of thyroxine (T 4) to triiodothyronine (T 3) by 2000g supernatants of fresh hepatic and renal homogenates. Administration of ATZ (29 ± 1 mg/kg body wt/day) in the diet for 2 weeks to male rats reduced hepatic and renal T 3 generation to 7 and 15% of control, respectively. This was associated with a significant depression of serum T 3 and T 4 concentrations. Administration of T 4 (50 μg/kg body wt/day) in combination with ATZ increased hepatic and renal T 3 generation to 135 and 182% of control levels, respectively. T 4 concentration in the serum of this group was significantly higher, while T 3 concentration was significantly lower, than in control rats. The addition of ATZ (10 −2 or 10 −4 m) to the incubation medium in vitro did not affect significantly the T 3 generation by control hepatic and renal homogenates. The results of this study suggest that the action of ATZ on peripheral deiodination of T 4 may be indirect and secondary to inhibition of the synthesis of thyroid hormones and resulting hypothyroidism.

The influence of testosterone propionate on thyroid function of immature rainbow trout, Salmo gairdneri Richardson

Testosterone propionate (TP) was injected intramuscularly (five injections at 4-day intervals) into fed immature rainbow trout at 11–12°; controls were sham injected. TP increased thyroxine (T 4) degradation rate, T 4 deiodination rate, T 4 conversion to 3,5,3′-triiodo- l-thyronine (T 3), plasma T 3 levels, and thyroid uptake of radioiodide 48–96 hr after radioiodide injection. However, plasma T 4 levels responded inconsistently to TP, while thyroid radioiodide uptake measured earlier than 24 hr was suppressed by TP. In conclusion, (i) TP, either directly or indirectly, stimulates many aspects of thyroid function, including conversion of T 4 to T 3, and (ii) plasma T 4 level and thyroidal uptake of radioiodide can be highly misleading indexes of thyroid function.

Microsomal Thyroxine Measurements with Iodide Selective Membrane Electrodes

Abstract An iodide membrane electrode, in conjunction with rat liver microsomes, is used to measure thyroxine at sub-micromolar levels. The microsomes serve as biocatalytic reagents which selectively remove iodide from the hormone. The amount of iodide liberated, as measured by the electrode, is proportional to the initial thyroxine concentration. The electrode can further be employed to directly monitor the rate of deiodination of the hormone with advantages of speed and convenience over existing techniques.

Role of thyroid gland in oxygen toxicity.

The effects of hyperoxia at ambient pressure on thyroid function and thyroid hormone metabolism have been assessed. Thyroidal activity was depressed in mice and rats by exposure to hyperoxia, due at least in part to a decrease in the rate of secretion of pituitary thyrotropin. The effects of hyperoxia on the peripheral deiodination of thyroxine (T4) were dependent on the concentration of oxygen employed and/or the duration of exposure; exposure to 40--80% oxygen for 96 h resulted in decreases in the rate of deiodination and in the deiodinative clearance of [125I]T4. Hyperoxia also resulted in a marked fall in the serum concentration of endogenous T4 and a decrease in T4-binding activity in serum. Many of these effects of hyperoxia were prevented by the concomitanat administration of large amounts of vitamin E (alpha-tocopherol acetate). These decreases in thyroid function and T4 metabolism were associated with a decrease in the rate of whole body oxygen consumption. Thus, the deleterious effects of oxygen in the rat were not due, even in part, to an oxygen-induced hyperthyroid state in the peripheral tissues.

In vivo determination of thyroxine deiodination rate in rainbow trout, Salmo gairdneri Richardson

An in vivo method is described for measuring the deiodination rate of l-thyroxine (T 4) and 3,5,3′-triiodo- l-thyroxine (T 3) in rainbow trout. The method is based on a comparison of plasma radioiodide kinetics following injection of either radioiodide or thyroid hormones phenolically labeled with radioiodine. It relies on a rapid turnover of thyroid hormones and a slow turnover of iodide in trout plasma. In two groups of 1-year-old trout starved for 3 days at 12°, 29.6 and 34.4% of the radioiodine were removed from labeled T 4 by deiodination; no deiodination of T 3 was detected. Assuming that T 4 undergoes phenolic monodeiodination to T 3, it was estimated that for the two groups of trout 59 and 69% of circulating T 4 were converted to T 3 and that rates of T 3 production from T 4 were 1.5 and 1.9 pmol/hr/100 g body weight.

Iodination-deiodination: A radiochemical method for detection of structure and changes in structure in RNA

Bound iodine is released from radioiodinated nucleotides in polymers exposed to sodium bisulfite. The rate of bisulfite-catalyzed deiodination of pyrimidines can be controlled both by change of temperature or pH and is also dependent on the molecular association of the nucleotide. The rate of release of iodine from iodocytidine in polycytidylate is greater than the rate of elimination from RNA. Experiments testing the influence of base-pairing of the iodopyrimidines in synthetic polynucleotides showed that pairing of the substituted nucleotide protected the iodine bond. The rates of bisulfite-catalyzed deiodination of several radioiodinated RNAs were measured. The action of bisulfite on all single stranded RNAs tested was multiphasic consisting of a rapid early deiodination reaction supplanted by a slower phase which was followed by reacceleration of release. The release of iodine from double stranded RNA and DNA-RNA duplexes was retarded in comparison with the release from ribosomal and messenger RNA fractions. The deiodination profiles of single and double stranded RNA suggested that the intermediate stage iodine release is governed by melting of paired zones of low stability. Late release may result from destabilization of the molecule through the addition of bisulfite to the pyrimidine ring or deamination. The effect of several substances expected to complex with polynucleotides was tested. Acridine orange and ethidium bromide increased loss of iodine from ribosomal RNA but slightly decreased elimination from double stranded viral RNA. A basic protein fraction isolated from ribosomal particles accelerated the deiodination of ribosomal RNA. While the destabilization caused by this protein fraction was greater than that caused by an equal amount of albumin, as tested the effect was non-specific. The results show that a change in sensitivity to chemical deiodination may follow the interaction of small amounts of protein with polynucleotides.

Differences in the sites of iodination of proteins following four methods of radioiodination

The rate of deiodination of radioiodinated proteins varies with the method of iodination. To elucidate differences in the iodinated protein labeled by various methods, we have hydrolyzed fibrinogen and several small peptides iodinated by the iodine monochloride, chloramine-T, electrolytic and enzymatic methods. Under conditions of either acidic or basic proteolysis, extensive deiodination occurred and the major product was I −. When a protease of Streptomyces griseus was used, radioiodinated fibrinogen and other polypeptides were degraded to single iodinated amino acid residues and only a small yield of I −. The iodinated amino acids resulting from proteolysis were separated by ion-exchange chromatography. The iodine monochloride and enzymatic methods yielded largely iodotyrosine with small amounts of other iodinated amino acids. The chloramine-T product spectrum varied with the chloramine-T:protein ratio, whereas the electrolytic method yield was a complex function of the reaction conditions. The different methods of iodination lead to some differences in the site of iodination which correlate with stability of the protein-iodine bond.

DYNAMIC STUDY OF POST-NATAL THYROID FUNCTION IN THE RAT

The thyroid function in development was investigated in post-natal rats. The thyroid iodine content rapidly increased from birth (137 +/- 26 ng iodine/mg thyroid) up to day 10 (338 +/- 42 ng iodine/mg thyroid) then increased more slowly up to day 30 (425 +/- 34 ng iodine/mg thyroid). The maximal plasma concentration of thyroxine was observed on day 16 (56.9 +/- 3.5 ng T4/ml) and of iodide on day 10 (110.2 +/- 12.6 ng I-/ml). The turnover rate constant of extrathyroidal thyroxine was higher at birth (8.0 +/- 2.3 %/h) than at any older age studied (average 6 %/h). Thyroxine secretion by the thyroid was more intense before weaning (37 ng hormonal iodine/h/100 g body weight on days 10 and 20) than after weaning (22 +/- 6 ng hormonal iodine/h/100 g body weight in 30 days old rats). The peripheral deiodination rate of thyroxine represented about 90 % thyroxine secretion rate in newborn and 10 days old rats and only 40% in adult females. In pre-weaning rats, after a single injection of both [131I]L-T4 and [125I]Na, extrathyroidal radioactivity disappeared more slowly than in 30 days old rats and adult animals. This suggests that iodide concentrations of extrathyroidal tissues are higher before than after weaning.

Photochemical studies and ultraviolet sensitization of Escherichia coli thymidylate kinase by various halogenated substrate analogs.

The effect of 5-iodo-2'-deoxyuridine monophosphate (IdUMP), various 5-halogenated-5'-azido-2', 5' -dideoxyuridine derivatives, 2'-deoxy-6-azauridine (AzdUrd), and its halogenated analogs on the ultraviolet sensitization of Escherichia coli thymidylate kinase has been investigated. Only those compounds iodinated in position 5 enhance the rate of ultraviolet inactivation of this enzyme. However, 5'-azido nucleosides with iodo, bromo, chloro, or fluoro substituents in position 5 neither protect nor sensitize thymidylate kinase to ultraviolet inactivation. Thymidine 5'-monophosphate partially protects the enzyme against ultraviolet inactivation either in the presence or absence of ultraviolet-sensitizing iodinated analogs. Magnesium ion does not enhance the ultraviolet inactivation of thymidylate kinase by 5-iodinated nucleoside analogs. The kinatic data support an active site-directed enhancement of the enzyme to ultraviolet inactivation by 5-iodo-2'-deoxyuridine monophosphate, since the concentration of IdUMP required to attain 50% maximal enhancement is 0.24 mM which is in good agreement with its Ki of 0.18 mM. When either [125I]IdUMP or [2-14C]IdUMP was irradiated with the enzyme, both radioactivities were associated with the enzyme, however only with the 14C analog was the amount bound at half-saturation essentially equal to the amount required to inactivate the enzyme by 50%. These data support the hypothesis that the active entity in the enhancement by IdUMP of thymidylate kinase inactivation during ultraviolet irradiation is the uridylate free radical which is formed photochemically from IdUMP. Photochemical studies of 6-azauracil (AzUra), 2'-deoxy-6-azauridine, and 5-iodo-2'-deoxy-6-azauridine (IAzdUrd) were performed. Photolysis of IAzdUrd in the presence of a hydrogen donor yields AzdUrd which upon further photolysis yields the photohydrate. The photohydrate of AzdUrd when incubated in the dark at pH 5.2 is 90% converted back to AzdUrd, whereas the photohydrate of AzUra is only partially (20%) converted to AzUra. The rate of deiodination of IAzdUrd is 2.1-fold greater than that of IdUMP. Although the Ki of IdUMP and IAzdUrd is similar, the increased photosensitivity of the aza analog accounts for the much greater enhancement of ultraviolet inactivation of thymidylate kinase. The ability of a compound to enhance the ultraviolet inactivation of deoxythymidylate kinase is correlated with the potential of the compound to produce a free radical rather than a photohydrate when the enzyme-substrate analog complex is irradiated.

Deiodinating activity of the liver and kidney tissue in the reptile

1. 1. Deiodinating activity of mono-iodotyrosine of liver and kidney in Geoclemys reevesii, Gekko gecko and Elaphe taeniura was examined. 2. 2. Deiodination was assessed by measuring 125I during a 20-min incubation of liver or kidney homogenate in a buffered medium containing 125I-MIT. 3. 3. No deiodinating activity was shown in liver and kidney of snake, and the kidney of turtle. 4. 4. The rate of MIT deiodination in the liver and kidney of gecko was similar (4 −6 × 10 −4 μg/min/mg tissue), and was 4-fold greater than the liver of turtle.

Thyroxine metabolism in the rat: effect of varying doses of exogenous thyroxine.

Experiments were performed to determine quantitatively the peripheral metabolism of exogenous thyroxine (T4) in rats brought to isotopic equilibrium with doses of -131I-T4 ranging from 1 to 20 mug/100 g body weight/day. It was found that, although the absolute amount of T4 either deiodinated and excreted as iodide in urine or excreted as T4 in faeces increased as the dose of T4 increased, the percentage of hormone excreted by either pathway at each dose level was relatively constant. In other words, the fractional rate of deiodination is not greatly influenced by the amount of T4 administered. A 20-fold increase in the dose of T4 resulted in only a 4-fold increase in serum T4 concentration measured 24 h after injection, but serum T4 levels were elevated considerably more than this for several hours between injections. Nevertheless, the highest dose of T4 was not greatly thyrotoxic. The implications of these findings in relation to the possible association between the metabolism and action of T4 are discussed.

Antagonistic effects of dinitrophenol and cyanide on hepatic thyroxine deiodination.

ABSTRACT Dinitrophenol inhibits the deiodination of thyroxine by the isolated perfused rat liver; the effect is reversible. Subsequent addition of cyanide to the perfusion fluid opposes the inhibitory effect of dinitrophenol and restores the deiodination rate to normal. However, addition of cyanide alone has little effect. Similar results are obtained with triiodothyronine.