Thyroid hormone action on mitochondria. IV. Redox states of intrinsic pyridine nucleotides in hypothyroidism, and influence of L-thyroxine.
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 microM L-thyroxine to hypothyroid mitochondria in 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 microM dinitrophenol in 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.
Hoch
F L
FL
University of Michigan Medical School, Department of Internal Medicine, Ann Arbor 48104, USA.
D000818:Animals; D005453:Fluorescence; D007037:Hypothyroidism / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism
D013963:Thyroid Hormones; D009249:NADP; D013974:Thyroxine