Phosphorylation of McArdle phosphorylase induces activity.

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Abstract
In McArdle disease, myophosphorylase deficiency, enzyme activity is absent but the presence of an altered enzyme protein can frequently be demonstrated. Phosphorylation of this protein in vitro evidently can result in catalytic activity. Muscle of 4 patients was studied; all lacked myophosphorylase activity, but myophosphorylase protein was demonstrated by immunodiffusion or gel electrophoresis. Incubation of muscle homogenate supernatants with cAMP-dependent protein kinase and ATP resulted in phosphorylase activity. The activated enzyme comigrated with normal human myophosphorylase in gel electrophoresis. Incubation with [.gamma.-32P]ATP resulted in incorporation of 32P into the band possessing phosphorylase activity. Activation of phosphorylase by cAMP-dependent protein kinase was inhibited by antibodies to normal human myophosphorylase or by inhibitory protein to cAMP-dependent protein kinase. Incubation of muscle homogenates with phosphorylase b kinase and ATP resulted in phosphorylase activity. After the action of cAMP-dependent protein kinase, the resulting activity was similar to that of phosphorylase b. Incubation with phosphorylase kinase resulted in activity similar to that of phosphorylase a. McArdle disease is probably not due to lack of normal phosphorylation, but restoration of activity to the mutant protein by phosphorylation may provide a clue to understanding the mechanism of this genetic defect.

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