The long-term objective of this proposal is to provide insight into the molecular basis for the different biochemical and physiological capabilities of fetal, maturing and adult heart and muscle. In fetal heart, energy production is very dependent on glycolysis; whereas, the adult heart preferentially produces energy via oxidative phosphorylation although glycolysis may be used as a compensatory mechanism for ATP production. The fetal skeletal muscle relies largely on an oxidative energy supply, but during maturation skeletal muscle becomes increasingly dependent on glycolysis. In both heart and skeletal muscle regardless of the developmentla state, the rate of glycolysis is primarily regulated by phosphofructokinase (PFK). In order to better understand this phenomenon, we propose to study the regulation of the activity as well as the concentration of the PFK isozymes in fetal, maturing and adult rat heart and skeletal muscle. More specifically, we propose to measure the levels and metabolism of the recently to more accurately establish the time course of changes of the two PFK isozymes by DEAE-cellulose chromatography, agarose gel electrophoresis, and immunological techniques. Also, the role of synthesis in proviking changes in the levels of the PFK isozymes will be determined by immunopresipitation of the radiolabelled PFK isozymes with specific antisera. Since the PFK regulatory factor is thought to regulate liver PFK concentration, we will measure its levels in fetal, neonatal, and adult rat heart and muscle. The results of these studies should be enlightening as to the molecular basis for the differences in glucose utilization between fetal, maturing and adult heart and muscle. Further, a better understanding of the changes that occur during development and maturation is required for improved medical treatment and health care of the fetus, neonate, and maturing child.
Showing the most recent 10 out of 19 publications
