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. 1987 May 15;244(1):137–142. doi: 10.1042/bj2440137

The effect of experimental hypothyroidism on phosphofructokinase activity and fructose 2,6-bisphosphate concentrations in rat heart.

A Gualberto 1, P Molinero 1, F Sobrino 1
PMCID: PMC1147964  PMID: 2959271

Abstract

Experimental hypothyroidism was induced in rats by the administration of NaClO4. Hearts from normal and hypothyroid rats were homogenized, and the extracts were assayed for phosphofructokinase-1 and phosphofructokinase-2 activity and fructose 2,6-bisphosphate concentrations. Hypothyroidism was associated with a drastic loss of phosphofructokinase-1 activity. A hyperbolic relationship between plasma thyroxine concentrations and phosphofructokinase-1 activity was found. As treatment with NaClO4 progressed, the decrease in blood thyroxine was faster than the decrease in enzyme activity. After prolonged hypothyroidism (a decrease in thyroxine of more than 10-fold), a 4-fold decrease in phosphofructokinase-1 activity was observed. In this metabolic condition 2-fold decreases in phosphofructokinase-2 activity and in fructose 2,6-bisphosphate were observed. A similar decrease in phosphofructokinase-1 activity in a partially purified preparation was found. The addition of L-thyroxine in the diet had little effect on phosphofructokinase-1 activity. However, exposure of minced pieces of hearts of hypothyroid rats to tri-iodothyronine for 5 h resulted in a clear increase in phosphofructokinase-1 activity, which was partially prevented by the simultaneous addition of cycloheximide. These results could account for the decrease in carbohydrate metabolism in heart from hypothyroid rats.

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Selected References

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  1. Alexander W. D., Wolff J. Thyroidal iodide tranpsort. 8. Endocrinology. 1966 Mar;78(3):581–590. doi: 10.1210/endo-78-3-581. [DOI] [PubMed] [Google Scholar]
  2. Bargoni N., Grillo M. A., Rinaudo M. T., Fossa T., Tourn M. L., Bozzi M. L. Uber die Glykolyse und Gluconeogenese in der Leber von hypothyreotischen Ratten. Hoppe Seylers Z Physiol Chem. 1966;344(1):42–49. [PubMed] [Google Scholar]
  3. Burns A. H., Reddy W. J. Direct effect of thyroid hormones on glucose oxidation by isolated rat cardiac myocytes. J Mol Cell Cardiol. 1975 Aug;7(8):553–561. doi: 10.1016/0022-2828(75)90114-5. [DOI] [PubMed] [Google Scholar]
  4. Böttger I., Kriegel H., Wieland O. Fluctuation of hepatic enzymes important in glucose metabolism in relation to thyroid function. Eur J Biochem. 1970 Apr;13(2):253–257. doi: 10.1111/j.1432-1033.1970.tb00925.x. [DOI] [PubMed] [Google Scholar]
  5. Holness M. J., Palmer T. N., Sugden M. C. Effects of administration of tri-iodothyronine on the response of cardiac and renal pyruvate dehydrogenase complex to starvation for 48 h. Biochem J. 1985 Nov 15;232(1):255–259. doi: 10.1042/bj2320255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hue L., Blackmore P. F., Shikama H., Robinson-Steiner A., Exton J. H. Regulation of fructose-2,6-bisphosphate content in rat hepatocytes, perfused hearts, and perfused hindlimbs. J Biol Chem. 1982 Apr 25;257(8):4308–4313. [PubMed] [Google Scholar]
  7. KISSANE J. M., ROBINS E. The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem. 1958 Jul;233(1):184–188. [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Laker M. E., Mayes P. A. Effect of hyperthyroidism and hypothyroidism on lipid and carbohydrate metabolism of the perfused rat liver. Biochem J. 1981 Apr 15;196(1):247–255. doi: 10.1042/bj1960247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mansour T. E. Phosphofructokinase. Curr Top Cell Regul. 1972;5:1–46. [PubMed] [Google Scholar]
  11. Mansour T. E., Wakid N., Sprouse H. M. Studies on heart phosphofructokinase. Purification, crystallization, and properties of sheep heart phosphofructokinase. J Biol Chem. 1966 Apr 10;241(7):1512–1521. [PubMed] [Google Scholar]
  12. Newsholme E. A., Randle P. J. Regulation of glucose uptake by muscle. 7. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, on the concentrations of hexose phosphates, nucleotides and inorganic phosphate in perfused rat heart. Biochem J. 1964 Dec;93(3):641–651. doi: 10.1042/bj0930641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Novello F., Gumaa J. A., McLean P. The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver. Biochem J. 1969 Mar;111(5):713–725. doi: 10.1042/bj1110713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Obregón M. J., Santisteban P., Rodríguez-Peña A., Pascual A., Cartagena P., Ruiz-Marcos A., Lamas L., Escobar del Rey F., Morreale de Escobar G. Cerebral hypothyroidism in rats with adult-onset iodine deficiency. Endocrinology. 1984 Aug;115(2):614–624. doi: 10.1210/endo-115-2-614. [DOI] [PubMed] [Google Scholar]
  15. Oppenheimer J. H. Thyroid hormone action at the cellular level. Science. 1979 Mar 9;203(4384):971–979. doi: 10.1126/science.218285. [DOI] [PubMed] [Google Scholar]
  16. Ortiz-Caro J., Pastor R. M., Jolin T. Effects of KClO4 in propylthiouracil-hypothyroid rats. Acta Endocrinol (Copenh) 1983 May;103(1):81–87. doi: 10.1530/acta.0.1030081. [DOI] [PubMed] [Google Scholar]
  17. Pogson C. I., Randle P. J. The control of rat-heart phosphofructokinase by citrate and other regulators. Biochem J. 1966 Sep;100(3):683–693. doi: 10.1042/bj1000683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Randle P. J., Newsholme E. A., Garland P. B. Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):652–665. doi: 10.1042/bj0930652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rider M. H., Hue L. Activation of rat heart phosphofructokinase-2 by insulin in vivo. FEBS Lett. 1984 Oct 29;176(2):484–488. doi: 10.1016/0014-5793(84)81223-5. [DOI] [PubMed] [Google Scholar]
  20. Rider M. H., Hue L. Regulation of fructose 2,6-bisphosphate concentration in white adipose tissue. Biochem J. 1985 Jan 15;225(2):421–428. doi: 10.1042/bj2250421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Segal J., Coppens A., Ingbar S. H. The effect of thyroid status on the calmodulin content of several tissues in the rat. Endocrinology. 1985 May;116(5):1707–1711. doi: 10.1210/endo-116-5-1707. [DOI] [PubMed] [Google Scholar]
  22. Sobrino F., Gualberto A. Hormonal regulation of fructose 2,6-bisphosphate levels in epididymal adipose tissue of rat. FEBS Lett. 1985 Mar 25;182(2):327–330. doi: 10.1016/0014-5793(85)80326-4. [DOI] [PubMed] [Google Scholar]
  23. St Germain D. L., Galton V. A. Comparative study of pituitary-thyroid hormone economy in fasting and hypothyroid rats. J Clin Invest. 1985 Feb;75(2):679–688. doi: 10.1172/JCI111747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stadtman E. R. Allosteric regulation of enzyme activity. Adv Enzymol Relat Areas Mol Biol. 1966;28:41–154. doi: 10.1002/9780470122730.ch2. [DOI] [PubMed] [Google Scholar]
  25. Suko J. The calcium pump of cardiac sarcoplasmic reticulum. Functional alterations at different levels of thyroid state in rabbits. J Physiol. 1973 Feb;228(3):563–582. doi: 10.1113/jphysiol.1973.sp010100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tarui S., Kono N., Uyeda K. Purification and properties of rabbit erythrocyte phosphofructokinase. J Biol Chem. 1972 Feb 25;247(4):1138–1145. [PubMed] [Google Scholar]
  27. Uyeda K., Furuya E., Luby L. J. The effect of natural and synthetic D-fructose 2,6-bisphosphate on the regulatory kinetic properties of liver and muscle phosphofructokinases. J Biol Chem. 1981 Aug 25;256(16):8394–8399. [PubMed] [Google Scholar]
  28. Van Schaftingen E., Hue L., Hers H. G. Fructose 2,6-bisphosphate, the probably structure of the glucose- and glucagon-sensitive stimulator of phosphofructokinase. Biochem J. 1980 Dec 15;192(3):897–901. doi: 10.1042/bj1920897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Van Schaftingen E., Jett M. F., Hue L., Hers H. G. Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3483–3486. doi: 10.1073/pnas.78.6.3483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]

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