INFLUENCES OF THYROXINE AND INSULIN ON THE TURNOVER AND FATE OF HIGH-ENERGY PHOSPHATE

Abstract

Ingestion by the weanling rat of thyroxine in an amount greatly in excess of physiological requirements resulted in significant increases in the rates of turnover of the high-energy compounds phosphocreatine (PC), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) and in significant decreases in their concentrations in skeletal muscle. Nucleoside phosphorylase and myokinase activities and rates of pyrophosphate splitting of ATP and of utilization of ATP for nuclear syntheses were unaltered in thyrotoxic muscle. The findings suggest that increased extramitochondrial utilization of ATP for glycolysis may be the factor responsible for the increased phosphorylating capacity of the thyrotoxic animal. An effect of thyroxine on mitochondrial permeability as well as on rate of formation of the high-energy intermediate would appear to explain the observed results.A further enhancement of the already markedly elevated thyrotoxic rate of phosphorylation was effected by the superimposition of insulin. Insulin also effected increases in the concentrations of the high-energy compounds. It is apparent that insulin acts by reducing the utilization of ATP for phosphorylation of glucose and thus increases the mitochondrial availability of high-energy acceptor. This increased mitochondrial affinity for high-energy compounds results in an enhancement of mitochondrial energy transfer processes.The findings appear to involve both thyroxine and insulin in the control of cell structure.