Conversion of thyroxine (T4) and triiodothyronine (T3) and the subcellular localisation of the converting enzyme

Hesch, R. D.; Brunner, G.; Söling, H.D.

doi:10.1016/0009-8981(75)90031-5

Cited by 81 publications

(33 citation statements)

References 9 publications

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“…Determination of the intracellular pH (Table 1), representing mainly the pH of the cytosolic compartment (Soboll et al, 1980), allows the conclusion that the pH optimum in vitro of 6.5-6.9 of the L-thyroxine 5'-deiodinase of the endoplasmatic reticulum (Auf dem Brinke et al, 1979;Fekkes et al, 1979), which is a cytosolic orientated membrane-integrated enzyme (Kohrle & Hesch, 1979), corresponds well with the optimum of T3 production of liver perfused with medium of pH 7.2, which results in an intracellular pH of about 6.5. In contrast, hepatic content and net uptake of T4 and T3 are not dependent on pH (compare Tables 3 and 4) and agree well with previously published data from experiments using different perfusion systems (Flock & Owen, 1965;Hillier, 1972;Hesch et al, 1975;Jennings et al, 1979;Pardridge & Mietus, 1980;Carter et al, 1979). One major discrepancy between our model and some of those reports is the low disappearance and/or degradation of T3.…”

Section: Discussionsupporting

confidence: 91%

“…Significant output of T3 was detectable after 30 min (P <0.05) and remained linear for up to 120 min. This pattern was comparable with data reported by Flock & Owen (1965), Hesch et al (1975) and Jennings et al (1979). Interestingly, however, T3 output by the perfused rat liver was dependent on the pH of perfusion (Figs.…”

Section: T3 Contentsupporting

confidence: 92%

“…This could be the reason for the higher output and production rates of T3 (7-13%) than those reported previously (Hesch et al, 1975;Jennings et al, 1979). Characteristics of Fluorocarbon 43 medium could give one explanation, but up to now no data on binding properties of the Fluorocarbon 43 medium for iodothyronines are available.…”

Section: Discussionmentioning

confidence: 87%

“…& Owen, 1965;Hillier, 1972). After introduction of specific radioimmunoassays, hepatic T3 production from T4 was found by Hesch et al (1975) and by Jennings et al (1979;Jennings, 1981), but not by van der Heide (1980). From these experiments the enzymic character of 5'-deiodination of T4 in perfused rat liver became evident.…”

mentioning

confidence: 97%

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pH-dependency of iodothyronine metabolism in isolated perfused rat liver

Köhrle¹,

Müller²,

Ködding³

et al. 1982

Biochemical Journal

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1. Isolated livers from fed male rats were perfused for 2h 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'-deionination rate is controlled by the intracellular pH.Extrathyroidal enzymic deiodination of the thyroid hormone L-thyroxine (T4) to other iodothyronines results in both activation and inactivation of T4. One product, L-3,3',5-tri-iodothryonine (T3) represents a compound that is more active, in terms of metabolic action and effects, than T4, whereas the other product, L-3,3',5'-tri-iodothyronine (rT3) is regarded as calorigenically inactive (Jorgensen, 1978). The (two) enzyme(s) iodothyronine 5'-deiodinase and 5-deiodinase forming these different tri-iodothyronines exhibit different pH optima in rat liver microsomal fractions and liver homogenates in vitro [for a review, see Kohrle (1981)1. Uptake, deiodination and conjugation of iodothyronines by isolated perfused rat liver was initially detected by paper chromatography of the radiolabelled compounds (Briggs et al

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Section: Discussionsupporting

confidence: 91%

Section: T3 Contentsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 97%

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pH-dependency of iodothyronine metabolism in isolated perfused rat liver

Köhrle¹,

Müller²,

Ködding³

et al. 1982

Biochemical Journal

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“…Thyroxine (T4) is the major thyronine secreted by the thyroid gland and functions as a pro-hormone since its deiodination product, triiodothyronine (T3), is the active hormone. The family of enzymes that converts T4 into T3 is known as 5 -deiodinases, and two different tissue-specific isoforms have been characterized in vertebrates: type 1 (D1) and type 2 (D2) (Hesch et al 1975). D1 is a rapid enzyme producing T3 for local and systemic demands.…”

Section: Introductionmentioning

confidence: 99%

Liver 5'-deiodinase activity is modified in rats under restricted feeding schedules: evidence for post-translational regulation

Aceves

Escobar²,

Rojas-Huidobro³

et al. 2003

Journal of Endocrinology

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Restricted feeding schedules (RFSs) produce a behavioral activation known as anticipatory activity, which is a manifestation of a food-entrained oscillator (FEO). The liver could be playing a role in the physiology of FEO.Here we demonstrate that the activity of liver selenoenzyme deiodinase type 1 (D1), which transforms thyroxine into triiodothyronine (T3), decreases before food access and increases after food presentation in RFSs. These changes in D1 activity were not due to variations in D1 mRNA. In contrast, a 24 h fast promoted a decrease in both D1 activity and mRNA content. The adjustment in hepatic D1 activity was accompanied by a similar modification in T3-dependent malic enzyme, suggesting that the local generation of T3 has physiological implications in the liver. These results support the notion that the physiological state of rats under RFSs is unique and distinct from rats fed freely or fasted for 24 h. Data also suggest a possible role of hepatic D1 enzyme in coordinating the homeorhetic state of the liver when this organ participates in FEO expression.

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Serum Thyroid Hormone Levels in Patients With Liver Disease

Hepner¹,

Chopra²

1979

Arch Intern Med

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Conversion of thyroxine (T4) and triiodothyronine (T3) and the subcellular localisation of the converting enzyme

Cited by 81 publications

References 9 publications

pH-dependency of iodothyronine metabolism in isolated perfused rat liver

pH-dependency of iodothyronine metabolism in isolated perfused rat liver

Liver 5'-deiodinase activity is modified in rats under restricted feeding schedules: evidence for post-translational regulation

Serum Thyroid Hormone Levels in Patients With Liver Disease

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