Studies on glycogen phosphorylase

PART I GLYCOGEN PHOSPHORYLASE IN BRAIN, ILEUM AND UTERUS In recent years considerable attention has been devoted to the nature of the glycogen phosphorylase enzyme system in skeletal muscle, cardiac muscle and liver. It has been established that those factors which affect the action of this enzyme constitute a major metabolic control mechanism. Considerably less attention has been paid to this enzyme system in tissues which are known to contain low glycogen, stores. The present study constitutes a preliminary examination of glycogen phosphorylase in brain, uterus and ileum. It has been found that brain contains considerably higher phosphorylase activity than liver and is comparable to heart. Uterus and ileum contain enzyme levels comparable to that of liver. The data suggests that the enzyme exists in two forms in these three tissues, one active in the presence of adenosine-5'-monophosphate, the other active in the absence of this nucleotide. The enzyme in each tissue is thus very similar to the skeletal muscle enzyme, but different from that in liver. Preliminary evidence was also obtained which indicates that phosphorylase activating and inactivating enzymes were present. Levels of active phosphorylase were increased in brain and uterus in the presence of epinephrine. The intestinal smooth muscle enzyme failed to respond to epinephrine. The evidence, although preliminary, is consistent with the idea that catecholamine-induced muscle contraction is associated with phosphorylase activation. PART II SYNTHESIS AND ENZYMATIC DEGRADATION OF SEVERAL DE0XYRIB0NUCLE0SIDE-3',5’-MONOPHOSPHATES It is known, that the phosphorylase activating action of epinephrine is mediated through adenosine-3',5'-monophosphate. The metabolism of this important nucleotide is attracting widespread attention. In order to study its seemingly manifold actions, the need has arisen for structural analogues of the compound. Several ribonucleoside-3',5'-monophosphates have already been prepared. In the present work several deoxyribonucleoside-3’,5'-monophosphates were synthesized. These included the nucleoside-3’,5'-monophosphates of deoxyadenosine, deoxyinosine, and deoxyuridine. These compounds were shown to be hydrolysed by a phosphodiesterase from brain which is specific for nucleoside-3',5'-monophosphates. The product of the hydrolysis, in each case, was identified as the corresponding deoxyribonucleoside-5'-phosphate.Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat