SCIENCE@home

Factors affecting the activity of muscle phosphorylase b kinase.

E. Krebs,D. Graves,E. Fischer

Published 1959 in Journal of Biological Chemistry

ABSTRACT

Resting muscle contains a higher proportion of phosphorylase b than of phosphorylase a as determined by analysis of extracts (1). Under the influence of epinephrine (2, 3) or with muscle contraction (4), the amount of phosphorylase a increases. Two enzymes which arc involved in the interconversion of the two forms of phosphorylase have been described. One of these, phosphorylase 6 kinasc, catalyzes the phosphorylation of phosphorylase b by idenosine triphosphate to give phosphorylase a (5-7); the other enzyme, phosphorylase phosphatase,l catalyzes the hydrolytic cleavage of phosphate from phosphorylase a to give phosphorylase b (9). It appears reasonable to assume that the relative activities of these two enzymes would be important factors in determining the proportion of phosphorylase a and b in muscle (4, 11). It has been found that phosphorylase b kinase exists in fresh rabbit muscle extracts in a form that is inactive at pH 7.0 or below. The enzyme becomes highly active in this region when incubated for a short period of time with Ca++ ions. As it has been suggested that the release of bound Ca++ may be a link between excitation of muscle and contraction (12, 13) or that Ca++ may be mobilized and undergo transfer from one site to another in connection with muscle contraction (14, 15), it is possible that the present effect is related to an important control process. Activation of phosphorylase 6 kinase would result in the production of phosphorylase a, which in turn catalyzes the first step in glycogenolysis. The outstanding investigations of Sutherland et al. (16-18) have shown that the increased formation of active liver phosphorylase observed in the presence of epinephrine is mediated by adenosine 3’,5’-phosphoric acid formed from adenosine triphosphate. They also have observed the formation of this substance in other tissues including skeletal muscle. No explanation has been given, however, as to how this compound acts in shifting the balance between the active and inactive forms of phosphorylase. In the present investigation it is shown that in muscle extract the effect of adenosine 3’,5’-phosphoric acid is in the activation of phosphorylase b kinase. In the activation process, which is apparent when the kinase is assayed below its pH optimum, Mg++ ions and adenosine triphosphate are required for the cyclic nucleotide effect. A preliminary report of this work has been given (19).

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-10 of 10 references · Page 1 of 1

CITED BY

Showing 1-100 of 475 citing papers · Page 1 of 5

12345
Next