Thyroid hormones and the creatine kinase system in cardiac cells.
The paper reviews the current evidence on the role of thyroid hormones in regulating the creatine kinase energy transfer system at multiple structures in cardiac cells. 1) Thyroid hormones modulate the overall synthesis of phosphocreatine (PCr) by increasing the rate of mitochondrial oxidative phosphorylation. 2) Thyroid hormones regulate the total activity of creatine kinase and its isoenzyme distribution. In comparison with normal thyroid state (euthyroidism), hypothyroidism is characterized by decreased total creatine kinase activity owing to diminished fraction of creatine kinase. On the other hand, hyperthyroidism, while causing no change in total creatine kinase activity, leads to increased fractions of neonatal isoforms of creatine kinase, and, in case of prolonged hyperthyroidism, to decreased fraction of mitochondrial creatine kinase. The latter change is associated with partial uncoupling between mitochondrial creatine kinase and adenine nucleotide translocase reflected by decreased PCr/O ratio. 3) Hyperthyroidism leads to increased passive sarcolemmal permeability due to which the leakage of creatine along its concentration gradient occurs. As a result of (i) increased sarcolemmal permeability for creatine, (ii) uncoupling of mitochondrial PCr synthesis, and (iii) increased energy utilization rate the steady state intracellular PCr content decreases under hyperthyroidism which, in turn, increases the myocardial susceptibility to hypoxic damage. Thyroid state also modulates the protective effects of exogenous PCr on energetically depleted myocardium.
Seppet
E K
EK
Department of Pathophysiology, Medical Faculty, University of Tartu, Estonia.
Saks
V A
VA
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism*; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism; D007037:Hypothyroidism / Q000201:enzymology; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010725:Phosphocreatine / Q000096:biosynthesis / Q000494:pharmacology; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology
D013963:Thyroid Hormones; D010725:Phosphocreatine; D003402:Creatine Kinase; D002118:Calcium