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Thyroid hormone action on mitochondria

IV. Redox states of intrinsic pyridine nucleotides in hypothyroidism, and influence ofl-thyroxine

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Abstract

Measurements of fluorescence at >420 nm and extracted NADPH in mitochondria obtained from the livers of hypothyroid rats show that the addition of Pi, ADP and glutamate rapidly reduces over 90% of the total reducible intrinsic pyridine nucleotides in State 3, compared with 20% in normals. The total fluorescence intensity change and reducible NADP+ is about twice normal in hypothyroid mitochondria. Adding 6–30 µMl-thyroxine to hypothyroid mitochondriain vitro decreases and delays the substrate-induced reduction of pyridine nucleotides, and excludes both NADP+ from such reduction and NADPH from oxidation by added ADP + Pi, without changing the high NADP(H) content. The correcting actions of the hormone are rapidly reversed by albumin, probably by binding free hormone. Changes in respiration do not appear to account for these observations. There is indirect evidence for decreased phosphorylation of added ADP in hypothyroid mitochondria, and a correction by added hormone. The hormonal actions on NADP(H) redox reactions are not reproduced by 1 to 6 µM dinitrophenolin vitro.l-Thyroxine appears to specifically block the participation of NADP (H) in redox reactions in mitochondria from hypothyroid rats, perhaps by effecting a sequestration of the nucleotide, by inhibiting the pyridine nucleotide transhydrogenase, or by activating an energy-linked process that competes with transhydrogenation.

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Authors and Affiliations

  1. Departments of Internal Medicine and Biological Chemistry, The University of Michigan Medical School, 7696 Kresge Building, 48104, Ann Arbor, Michigan

    Frederic L. Hoch

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  1. Frederic L. Hoch
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Additional information

Papers I–III in this series were published inArch. Biochem. Biophys.

I–124 (1968) 238.

II–124 (1968) 248.

III–150 (1972) 618.

This work was supported by grants from the NIH (AM13564) and from The John A. Hartford Foundation.

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Hoch, F.L. Thyroid hormone action on mitochondria. J Bioenerg Biomembr 8, 223–238 (1976). https://doi.org/10.1007/BF00761448

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  • DOI: https://doi.org/10.1007/BF00761448

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