REGULATION OF GLYCOSIS IN THE AGING HEART

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The investigators propose to study the influence of aging on the control of glycolysis in heart. The specific aims include: 1) to isolate, purify and characterize the 6-phosphofructo 2-kinase of rat heart, the enzyme responsible for the synthesis of fructose 2,6-bisphosphate. 2) To determine whether the enzyme, originating from heart is bifunctional, as it is in liver, and whether the enzyme is susceptible to phosphorylation by cyclic AMP-dependent protein kinase, with resultant reciprocal changes in activities. 3) To study regulation of glycolysis in whole and separated discrete parts of the heart and im myocytes obtained from hearts of aging rats and of cardiomyopathic hamsters. These studies will include determination of levels of fructose 2,6-phosphate and the activities of 6-phosphofructo 2-kinase and 6-phosphofructo 1-kinase. In the same studies the activity of glycogen phosphorylase will also be studied. 4) These parameters will be determined in myocytes and fibroblasts of the heart, in order to learn whether the levels of fructose 2,6-bisphosphate and of 6-phosphofructose 2-kinase are modulated by various hormones and effectors. These studies will be correlated with those described in project 0004, dealing with hormone receptors. 5) Hearts from aging rats and from model cardiomyopathic hamsters will be studied to determine the capacity of the heart to synthesize creatine from guanidinoacetate under governance of guanidino methyltransferase.